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Synthesis 2025; 57(01): 71-83
DOI: 10.1055/a-2353-1722
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Special Topic Dedicated to Prof. H. Ila

Magnesium-Mediated Regioselective Additions of Bromoform to Quinone Methides and Aurone-Derived Azadienes

Deepak Kumar
,
Nishikant Satam
,
Irishi N. N. Namboothiri  ∗

I.N.N.N. thanks Science and Engineering Research Board (SERB), India for funding. D. K. Thanks CSIR India and N. S. thanks UGC India for a research fellowship.
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Abstract

The magnesium-mediated addition of bromoform to conjugated electron-deficient alkenes and imines, such as para-quinone methides (p-QMs) and aurone-derived azadienes, respectively, is reported here for the first time. While p-QMs undergo exclusive and hitherto unreported 1,6-addition of bromoform to afford benzylic tribromomethylated diarylmethanes, aurone-derived azadienes undergo both 1,2- and 1,4-additions to furnish α- and γ-tribromomethylamines. A mechanism involving the intermediacy of the tribromomethyl radical has been proposed based on control experiments and EPR studies. Representative synthetic transformations have also been carried out.


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Key words

magnesium-mediated addition - bromoform - conjugate addition - p-quinone methides - azadienes - diarylmethanes

Polyhalogenated organic compounds are present in numerous bioactive compounds,[1] including natural products.[2] For instance, TaBro A belongs to a special class of tetrahydro-β-carboline based potent neurotoxins (Figure [1]).[3] Tribromomethylated compounds are also present in the metabolites of Bonnemaisonia hamifera,[4] Delisea fimbriata,[5] and Asparagopis taxiformis.[6] Compound B, which is present in Asparagopis taxiformis, shows activity against aldose reductase and therefore is a potent diabetic inhibitor.[6] From synthetic point of view, the tribromomethylated compound C is a useful intermediate in the synthesis of many biologically important compounds, for example, the anti-anginal agent Zatebradine.[7]

The reaction of haloform with alkenes for the generation of polyhalomethylated and dihalocyclopropane derivatives under anionic (base/PTC)[8] [9] [10] and radical[11] conditions is well explored, but the metal-mediated bromoform addition remained relatively obscure.[12] We and others have been involved in the application of Mg-CHBr3 as a convenient reagent system for the addition of the CBr3 group to various electron-deficient alkenes.[12] Thus, the reaction of bromoform in the presence of magnesium with nitroalkenes,[13] chalcones,[14] sulfonyl/Boc imines,[15] nitrodienes,[16] and open-chain dibenzylidene ketones[16] primarily affords CBr3 adducts via conjugate addition (Scheme [1a,b]), which can, depending on the reaction conditions, be further selectively transformed into dibromomethylidenes,[13] cyclic ortho esters and γ-keto esters.[14] On the other hand, cycloalkanone-derived chalcones,[17] cyclic dibenzylidene ketones,[16] as well as 3-olefinic oxindoles[16] furnished spiro-cyclopropanated products that underwent Lewis acid catalyzed regioselective ring expansion to afford fused bromofurans via Cloke–Wilson rearrangement.

Zoom Image
Figure 1 Organic molecules of biological interest containing a tribromomethyl group

In our quest to explore the versatile reactivity of the Mg-CHBr3 reagent system with hitherto unexplored electrophiles and alternative modes of reactivity, we have chosen p-quinone methides[18] and aurone-derived azadienes,[19] which are key scaffolds for the synthesis of complex fused and spiro-heterocycles. This is also the first report of 1,2- and 1,6-additions of bromoform to conjugated electrophiles (Scheme [1], this work).

Encouraged by the results obtained by our group in the area of conjugate addition of bromoform to activated alkenes,[13] [14] [15] [16] [17] we proceeded to investigate the 1,6-addition of bromoform to p-QMs. Thus, p-QM 1a bearing the parent phenyl group afforded the Michael adduct 3a in 73% yield (Scheme [2]). There was no further intramolecular cyclization of this Michael adduct 3a to the cyclopropanation product. p-QMs 1b, 1c, and 1d bearing weakly electron-donating substituents, such as methyl and ethyl, at the ortho- and para-positions afforded the 1,6-adducts 3b, 3c, and 3d, respectively in 67%, 79%, and 73% yields. The one bearing strongly electron-donating methoxy group at the para-position 1e delivered the corresponding product 3e in marginally lower yield (66%). However, p-QMs 1f and 1g with similar substitution at the ortho- and meta-positions provided the corresponding Michael adducts 3f and 3g in good yields (80% and 73%, respectively). Substrates 1h–k possessing weakly electron-withdrawing halogens at ortho- and para-positions also furnished the corresponding Michael adducts 3h–k in good yields (71–78%). Fused, heteroaromatic and styrenyl derivatives 1l–o were subjected to bromoform addition under the standard conditions. While the β-naphthyl analogue 1l provided the product 3l in good yield (69%), the α-naphthyl analogue 1m furnished the product 3m only in slightly lower yield (66%). Notably, a heteroaryl analogue 1n delivered the desired 1,6-adduct 3n in comparable yield (64%). However, a drastic drop in the yield was observed in the case of styrenyl analogue 1o, wherein the 1,6-adduct 3o was isolated in much lower yield (51%). Unfortunately, the bulky diphenyl analogue 1p did not react leading to recovery of the starting material. On the other hand, the diisopropyl-substituted p-QM 1q also reacted well, yielding the desired product 3q in 70% yield.

Zoom Image
Scheme 1 Mg-mediated bromoform addition to activated alkenes
Zoom Image
Scheme 2 Scope of p-quinone methides. Reagents and conditions: p-QM 1 (0.2 mmol), Mg (1.6 mmol, 8 equiv), CHBr3 2 (4.4 mmol, 22 equiv), THF (5 mL); isolated yields after silica gel column chromatography. a No characterizable side product, such as 1,8-addition product, was observed in this reaction.

Overall, there was no major substituent effect in the above reaction as p-QMs bearing various substituted aryl and a heteroaryl reacted smoothly with bromoform to afford the corresponding 1,6-adducts 3a–n in good to excellent (64–80%) yields. On the other hand, while alteration of the electron density at the benzylic position via extended conjugation substantially diminished the yield (3o), additional substitution completely shut down the reaction (3p). Notably, a p-QM 1q bearing i Pr groups performed equally well compared to those bearing t Bu groups.

In order to examine the feasibility of the Mg-mediated bromoform addition to azadienes, we selected the unsubstituted aurone-derived azadiene 4a as the model substrate (Table [1]). Initially, we employed the established conditions and treated azadiene 4a with excess bromoform (22 equiv) in the presence of excess magnesium (8 equiv) in THF at room temperature (entry 1). Interestingly, we observed the formation of two products which were later identified as 1,2-adduct 5a (minor, 27% yield) and 1,4-adduct 6a (major, 48% yield). Desiring to improve the selectivity by varying the reaction conditions, the reaction was conducted at 0 °C, however, it did not progress even after 48 h (entry 2). Then we performed the reaction at higher temperatures, 50 °C and 65 °C (entries 3 and 4) and found that the yield and ratio remained comparable to those obtained at room temperature. Upon lowering the quantity of bromoform as well as Mg to 4 equiv each, longer reaction time and lower yields were encountered (entry 5). There was no significant conversion upon further decreasing the quantity of Mg and bromoform (entry 6). To enhance the selectivity of 1,4-addition product 6a, we screened various Cu salts amongst which CuBr and CuI failed to improve the selectivity (entries 7 and 8), and there was no reaction in the presence of CuOAc (entry 9). There was no reaction when CeCl3 was employed to improve the selectivity for the 1,2-addition (entry 10). Therefore, the already established conditions (entry 1) remained as the best to investigate the substrate scope.

Table 1 Optimization of Bromoform Addition to Aurone-Derived Azadiene 4a a

Entry

CHBr3 (equiv)

Mg (equiv)

Additive (10 mol%)

Time (h)

Temp (°C)

Yield (%)b of 5a

Yield (%)b of 6a

 1

CHBr3 (22)

Mg (8)

–

 2

 0 °C–rt

27

48

 2

CHBr3 (22)

Mg (8)

–

48

 0 °C

–c

–c

 3

CHBr3 (22)

Mg (8)

–

 2

50 °C

25

49

 4

CHBr3 (22)

Mg (8)

–

 2

65 °C

25

48

 5

CHBr3 (4)

Mg (4)

–

24

 0 °C–rt

12

30

 6

CHBr3 (2)

Mg (1)

–

24

 0 °C–rt

trace

trace

 7

CHBr3 (22)

Mg (8)

CuBr

 4

 0 °C–rt

19

40

 8

CHBr3 (22)

Mg (8)

CuI

 4

 0 °C–rt

12

35

 9

CHBr3 (22)

Mg (8)

CuOAc

24

 0 °C–rt

–c

–c

10

CHBr3 (22)

Mg (8)

CeCl3

24

 0 °C–rt

–c

–c

a Reaction scale: azadiene 4a (0.2 mmol), THF (5 mL).

b Yields after silica gel column chromatography.

c No reaction.

The formation of a mixture of 1,2- and 1,4-adducts 5a and 6a, respectively, in the addition of bromoform to azadiene 4a prompted us to investigate the scope of the reaction (Scheme [3]). Notably, azadienes 4b–d bearing weakly electron-withdrawing halogens at the para position afforded both the series of products 5b–d and 6b–d in slightly better yields and comparable ratios. On the other hand, o-chloro-substituted azadiene 4e delivered the two products 5e (CCDC: 2198473) and 6e (CCDC: 2198488) in marginally lower yields (20% and 42%, respectively), presumably due to steric factors. Similar yields for the 1,2- and 1,4-adducts 5f (22%) and 6f (42%), respectively, were also obtained for the azadiene 4f bearing a m-methoxy substituent. While azadiene 4g possessing a weakly electron-donating para-substituent (Me) afforded the corresponding products 5g and 6g in 25% and 43% yield, respectively, its methoxy analogue 4h provided only the 1,4-adduct 6h in 45% yield. Also, these conditions were well tolerable for the naphthyl-substituted azadiene 4i which afforded the two adducts 5i and 6i in 22% and 40% yield, respectively. To our surprise, bromo substitution on the benzofuran ring para to the ring oxygen as in 4j resulted in the formation of only the 1,2-adduct 5j in 41% yield.

Zoom Image
Scheme 3 Scope of aurone-derived azadienes. Reagents and conditions: azadiene 4 (0.2 mmol), Mg (1.6 mmol, 8 equiv), CHBr3 2 (4.4 mmol, 22 equiv), THF (5 mL); isolated yields after silica gel column chromatography.

In general, unlike in the reported cases and in the case of p-QM, aurone-derived azadienes 4 reacted with bromoform and afforded a mixture of 1,2- and 1,4-adducts 5 and 6, respectively, as minor and major products in good to excellent (62–84%) total yields with two notable exceptions. While the p-methoxyphenyl analogue 4h furnished only the 1,4-adduct 6h, the one with bromine on the benzo ring 5j afforded only the 1,2-adduct 5j, both in moderate yield. Formation of 1,4-adduct 6 as the major product, despite the deactivating effect by the ring oxygen towards 1,4-addition, is attributable to retention of aromaticity of the furan ring in the benzofuran of 6 which is formed via 1,4-addition. This is amplified in 4h due to the para-methoxy group entering into extended conjugation with the imine moiety thereby making the β-position more electrophilic. It is also obvious that the ring oxygen facilitates 1,2-addition, though the minor pathway, via its conjugation with the imine moiety through the benzo ring. This is more pronounced in the case of 4j bearing a weakly electron-withdrawing group (Br) on the benzo ring leading to exclusive formation of 1,2-adduct 5j.

Zoom Image
Scheme 4 Proposed anionic mechanism
Zoom Image
Scheme 5 Proposed radical mechanism

Initially, two alternative mechanisms, anionic and radical, were considered (Schemes 4 and 5). In the anionic mechanism, first, dibromomethylmagnesium bromide (I) is formed via oxidative addition of Mg to bromoform (Scheme [4]). Intermediate I then acts as a base and deprotonates bromoform to generate tribromomethylmagnesium bromide (II) which adds to acceptors 1 and 4. The addition of Grignard­ species across the activated double bond of azadiene 4 in 1,2- and 1,4-fashion results in the formation of intermediates IV and V respectively, while p-QM 1 undergoes 1,6-addition to give intermediate III.

In the alternative radical mechanism, first, dibromomethyl radical (VI) is formed via SET of Mg to bromoform (Scheme [5]). Intermediate VI then abstracts a hydrogen radical from excess bromoform to generate tribromomethyl radical (VII), which adds to acceptors 1 and 4. The addition of tribromomethyl radical across the activated double bond of azadiene 4 in 1,2- and 1,4-fashion results in the formation of intermediates IX and Xa,b respectively, while p-QM 1 undergoes 1,6-addition to give intermediates VIIIa,b. Further, aqueous workup leads to the formation of desired products 3–6.

In order to ascertain whether or not the reaction follows anionic or radical pathway, the reaction of p-QM 1a and azadiene 4a with Mg-bromoform was carried out in the presence of TEMPO (22 equiv) as radical scavenger (Scheme [6a,b]). Under these conditions, the reactions did not proceed and the starting materials 1a and 4a were recovered after 24 h. Further, the bromoform addition to azadiene 4a was carried out in the presence of another radical scavenger, cyclohexa-1,4-diene (22 equiv), which also led to complete recovery of starting material 4a after 12 h (Scheme [6c]). These control experiments suggested that the reaction follows the radical pathway. In order to unambiguously establish the mechanistic pathway, EPR analysis of the reaction mixture was carried out at t = 30 min. This showed a signal with g value 2.07 (ν = 9.387 GHz, H = 3241 T), confirming the presence of the CBr3 radical species (Figure S117).[13] However, there was no other characteristic signal that could be attributed to any of the species IX, Xa,b arising from substrate 4. This is in contrast to the evidence obtained from EPR for both CBr3 radical species and a nitroalkyl radical species that was presumably generated via Mg-mediated addition of bromoform to nitroalkene.[13] In view of the above, it can be concluded that either the substrate radical species IX–X are too transient to be detected by EPR or the initially formed CBr3 radical VII is converted into the CBr3 anion II via single electron transfer from Mg and then the nucleophilic addition of II to the substrate takes place (Schemes 4 and 5).

Zoom Image
Scheme 6 Control experiments
Zoom Image
Scheme 7 Scale-up and synthetic transformations of tribromomethylated adducts

Further, the scalability of our methodology was demonstrated. Thus, scale-up synthesis of tribromomethylated 1,6-adduct 3a and tribromomethylated 1,2- and 1,4-adducts of aurone-derived azadienes 5a and 6a, respectively, was carried out without significant decrease in overall yields (Scheme [7a,b]). A representative synthetic application of the tribromomethylated product p-QM 3 was also investigated. Thus, p-QM 3f was successfully transformed into its corresponding dibromomethylenated adduct 7 in excellent yield via TBAF-mediated one-pot dehydrobromination and TBDMS deprotection in THF at room temperature (Scheme [7c]). On the other hand, the tribromo compound 6f undergoes HBr elimination with 3 equiv of KOH in methanol at room temperature to give the corresponding dibromomethylenated derivative 8 in 78% yield (Scheme [7d]). Furthermore, to examine the stability and synthetic applicability of the products, a representative compound 3k was subjected to de-tert-butylation using AlCl3 under standard conditions (Scheme [7e]). Surprisingly, only one tert-butyl group was removed to afford product 9 in excellent yield (87%). Attempted removal of both the tert-butyl groups by adding excess AlCl3 and/or heating led to decomposition.

In conclusion, for the first time, we have demonstrated a very simple and facile 1,6-addition of bromoform to p-QMs in the presence of magnesium to provide the tribromomethylated 1,6-adducts in good to high yields in most cases and a further transformation to dibromomethylenated adduct under mild conditions. On the other hand, similar addition of bromoform to aurone-derived azadienes afforded a mixture of 1,2- and 1,4-adducts in approximately 1:2 ratio in good to excellent total yields in most cases. These tribromomethylated compounds are also amenable for further transformation into dibromomethylenated products via HBr elimination. Our control experiments and EPR analysis confirmed the intermediacy of a CBr3 radical species in the reaction.

The melting points recorded are uncorrected. NMR spectra (1H, 1H decoupled 13C and 1H-1H COSY) were recorded with TMS as the internal standard. HRMS were recorded under ESI Q-TOF conditions. Single crystals suitable for X-ray analysis were prepared via slow evaporation of a CH2Cl2/petroleum ether (PE) (1:2) solution of the sample at rt. The single-crystal diffraction data of the complex was collected on a Bruker diffractometer with MoKα radiation (λ = 0.71073 Å). Data reduction and the unit cell parameters were determined by using CrysalisPro171.40.64.53. With the help of Olex2 software with the SHELXL program, crystal data was solved by direct method and refined by the least square procedure. All non-hydrogen atoms were refined anisotropically and the positions of all hydrogen atoms were generated geometrically. EPR measurement was conducted at 4 K using a Bruker-EMXplus model, X-band (9.5 GHz) spectrometer. p-QMs 1 [20] and azadienes 4 [19b] [21] were prepared from corresponding aldehydes and acetophenones by the literature method.


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Tribromomethyl Adducts 3, 5, and 6; General Procedure

To a stirred mixture of p-quinone methide 1 (0.29 g, 1 mmol, 1 equiv)/azadiene 4 (0.38 g, 1 mmol, 1 equiv), and Mg (0.19 g, 8 atom g, 8 equiv) in THF (20 mL) was added CHBr3 (2 mL, 22 mmol, 22 equiv) dropwise over a period of 10 min at 0 °C. The mixture was gradually brought to rt over a period of 1–3 h during which the solution turned dark brown. The mixture was subsequently quenched with sat. aq NH4Cl (8 mL). The aqueous layer was extracted with EtOAc (4 × 10 mL) and the combined organic layers were dried (anhyd Na2SO4) and concentrated in vacuo to afford the crude product, which was purified by column chromatography (silica gel, PE/EtOAc, 19:1, gradient elution).


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2,6-Di-tert-butyl-4-(2,2,2-tribromo-1-phenylethyl)phenol (3a)

White solid; yield: 394 mg (73%); mp 145–147 °C.

IR (neat): 3620 (s), 2964 (vs), 2874 (s), 1599 (w), 1494 (m), 1438 (vs), 1360 (m), 1319 (m), 1264 (s), 1245 (m), 1152 (s), 1123 (m), 880 (m), 810 (m), 764 (s), 741 (vs), 704 (vs), 646 (m), 628 cm–1 (m).

1H NMR (400 MHz, CDCl3): δ = 1.44 (s, 18 H), 5.12 (s, 1 H), 5.22 (s, 1 H), 7.30–7.38 (m, 3 H), 7.50 (s, 2 H), 7.74 (d, J = 6.9 Hz, 2 H).

13C {1H} NMR (100 MHz, CDCl3): δ = 30.5, 34.6, 50.0, 73.5, 127.3, 127.9, 128.3, 129.8, 129.9, 135.3, 140.4, 153.6.

HRMS (ES+, Ar): m/z [M – HBr]H+ calcd for C22H27 79Br2O: 465.0429; found: 465.0417.


#

2,6-Di-tert-butyl-4-(2,2,2-tribromo-1-(p-tolyl)ethyl)phenol (3b)

White solid; yield: 375 mg (67%); mp 118–120 °C.

IR (neat): 3635 (s), 2960 (vs), 1645 (w), 1513 (m), 1436 (vs), 1392 (m), 1361 (m), 1321 (m), 1254 (s), 1237 (s), 1208 (m), 1156 (s), 1122 (m), 1023 (m), 893 (m), 810 (m), 740 (vs), 705 (m), 679 (m), 648 (w), 632 cm–1 (w).

1H NMR (400 MHz, CDCl3): δ = 1.45 (s, 18 H), 2.35 (s, 3 H), 5.10 (s, 1 H), 5.21 (s, 1 H), 7.18 (d, J = 8.1 Hz, 2 H), 7.51 (s, 2 H), 7.64 (d, J = 8.1 Hz, 2 H).

13C {1H} NMR (100 MHz, CDCl3): δ = 21.3, 30.6, 34.6, 50.6, 73.2, 127.2, 129.0, 129.8, 130.0, 135.3, 137.4, 137.7, 153.6.

HRMS (ES+, Ar): m/z [M – HBr]H+ calcd for C23H29 79Br2O: 479.0585; found: 479.0586.


#

2,6-Di-tert-butyl-4-(2,2,2-tribromo-1-(4-ethylphenyl)ethyl)phenol (3c)

White solid; yield: 450 mg (79%); mp 112–114 °C.

IR (neat): 3635 (s), 2963 (vs), 2872 (s), 1661 (w), 1645 (w), 1512 (m), 1436 (vs), 1391 (w), 1361 (m), 1321 (m), 1264 (m), 1237 (s), 1157 (s), 1122 (m), 1022 (w), 892 (m), 882 (m), 855 (m), 837 (m), 809 (m), 771 (m), 739 (s), 677 (m), 648 (w), 632 cm–1 (w).

1H NMR (500 MHz, CDCl3): δ = 1.18 (t, J = 7.5 Hz, 3 H), 1.38 (s, 18 H), 2.59 (q, J = 7.5 Hz, 2 H), 5.03 (s, 1 H), 5.15 (s, 1 H), 7.14 (d, J = 8.0 Hz, 2 H), 7.45 (s, 2 H), 7.60 (d, J = 8.0 Hz, 2 H).

13C {1H} NMR (125 MHz, CDCl3): δ = 15.4, 28.6, 30.6, 34.6, 50.7, 73.3, 127.2, 127.8, 129.9, 130.1, 135.3, 137.6, 143.9, 153.6.

HRMS (ES+, Ar): m/z [M – HBr]H+ calcd for C24H31 79Br2O: 493.0742; found: 493.0740.


#

2,6-Di-tert-butyl-4-(2,2,2-tribromo-1-(o-tolyl)ethyl)phenol (3d)

White solid; yield: 404 mg (73%); mp 169–171 °C.

IR (neat): 3631 (s), 2963 (vs), 2874 (m), 1462 (m), 1435 (s), 1321 (w), 1289 (vw), 1236 (m), 1155 (m), 1122 (w), 891 (w), 848 (vw), 809 (w), 757 (w), 730 (s), 685 (m), 646 (w), 625 cm–1 (w).

1H NMR (500 MHz, CDCl3): δ = 1.43 (s, 18 H), 2.40 (s, 3 H), 5.23 (s, 1 H), 5.41 (s, 1 H), 7.16 (d, J = 7.3 Hz, 1 H), 7.21 (t, J = 7.3 Hz, 1 H), 7.16 (t, J = 7.3 Hz, 1 H), 7.47 (s, 2 H), 8.32 (d, J = 7.9 Hz, 1 H).

13C {1H} NMR (125 MHz, CDCl3): δ = 20.9, 30.5, 34.5, 50.1, 67.6, 126.0, 126.2, 127.5, 128.1, 128.4, 131.0, 135.0, 136.6, 139.9, 153.6.

HRMS (ES+, Ar): m/z [M – HBr]H+ calcd for C23H29 79Br2O: 479.0585; found: 479.0591.


#

2,6-Di-tert-butyl-4-(2,2,2-tribromo-1-(4-methoxyphenyl)ethyl)phenol (3e)

White solid; yield: 380 mg (66%); mp 114–116 °C.

IR (neat): 3636 (m), 2959 (vs), 2922 (s), 1609 (m), 1512 (vs), 1437 (vs), 1305 (w), 1264 (vs), 1181 (m), 1156 (m), 1121 (w), 1036 (m), 909 (w), 835 (w), 788 (w), 758 (s), 735 (m), 679 cm–1 (w).

1H NMR (400 MHz, CDCl3): δ = 1.43 (s, 18 H), 3.80 (s, 3 H), 5.06 (s, 1 H), 5.20 (s, 1 H), 6.89 (d, J = 7.4 Hz, 2 H), 7.48 (s, 2 H), 7.65 (d, J = 7.4 Hz, 2 H).

13C {1H} NMR (100 MHz, CDCl3): δ = 30.6, 34.6, 51.2, 55.4, 72.8, 113.6, 127.0, 130.2, 131.2, 132.5, 135.3, 153.5, 159.2.

HRMS (ES+, Ar): m/z [M – HBr]H+ calcd for C23H29 79Br2O2: 495.0534; found: 495.0549.


#

2,6-Di-tert-butyl-4-(2,2,2-tribromo-1-(2-(tert-butyldimethylsil­oxy)phenyl)ethyl)phenol (3f)

White solid; yield: 540 mg (80%); mp 166–168 °C.

IR (neat): 3836 (m), 3746 (w), 3629 (m), 3297 (br w), 2954 (vs), 1487 (m), 1453 (m), 1435 (m), 1285 (w), 1254 (m), 1049 (vs), 1032 (vs), 920 (m), 840 (w), 824 (w), 778 (w), 753 cm–1 (w).

1H NMR (400 MHz, CDCl3): δ = 0.29 (s, 3 H), 0.32 (s, 3 H), 1.11 (s, 9 H), 1.43 (s, 18 H), 5.20 (s, 1 H), 5.97 (s, 1 H), 6.83 (dd, J = 8.1, 1.1 Hz, 1 H), 7.01 (td, J = 8.1, 1.1 Hz, 1 H), 6.83 (td, J = 8.1, 1.1 Hz, 1 H), 7.56 (s, 2 H), 8.24 (dd, J = 8.1, 1.1 Hz, 1 H).

13C {1H} NMR (100 MHz, CDCl3): δ = –3.9, –3.4, 18.5, 26.2, 30.5, 34.6, 51.3, 62.8, 118.2, 120.7, 128.2, 128.3, 128.5, 128.9, 131.7, 135.0, 153.4, 153.5.

HRMS (ES+, Ar): m/z [M + H]+ calcd for C28H42 79Br3O2Si: 675.0504; found: 675.0506.


#

2,6-Di-tert-butyl-4-(2,2,2-tribromo-1-(3-methoxyphenyl)ethyl)phenol (3g)

White solid; yield: 420 mg (73%); mp 111–113 °C.

IR (neat): 3631 (s), 2960 (vs), 2872 (m), 2835 (vw), 1599 (s), 1584 (m), 1491 (s), 1436 (vs), 1320 (m), 1263 (vs), 1238 (s), 1210 (m), 1154 (s), 1052 (m), 913 (vw), 881 (w), 809 (w), 771 (m), 739 (s), 708 (s), 689 (m), 607 cm–1 (w).

1H NMR (500 MHz, CDCl3): δ = 1.44 (s, 18 H), 3.82 (s, 3 H), 5.07 (s, 1 H), 5.22 (s, 1 H), 6.86 (d, J = 7.5 Hz, 1 H), 7.28 (t, J = 7.5 Hz, 1 H), 7.32 (s, 1 H), 7.34 (d, J = 7.5 Hz, 1 H), 7.50 (s, 2 H).

13C {1H} NMR (125 MHz, CDCl3): δ = 30.5, 34.6, 49.8, 55.4, 73.3, 113.1, 115.8, 122.3, 127.4, 129.2, 129.6, 135.3, 141.8, 153.7, 159.4.

HRMS (ES+, Ar): m/z [M – HBr]H+ calcd for C23H29 79Br2O2: 495.0534; found: 495.0544.


#

2,6-Di-tert-butyl-4-(2,2,2-tribromo-1-(4-bromophenyl)ethyl)phenol (3h)

White solid; yield: 468 mg (75%); mp 139–141 °C.

IR (neat): 3629 (s), 2959 (vs), 2874 (m), 1488 (m), 1437 (s), 1238 (m), 1156 (m), 1076 (m), 734 (s), 710 cm–1 (s).

1H NMR (500 MHz, CDCl3): δ = 1.45 (s, 18 H), 5.10 (s, 1 H), 5.25 (s, 1 H), 7.45 (s, 2 H), 7.49 (d, J = 8.4 Hz, 2 H), 7.62 (d, J = 8.4 Hz, 2 H).

13C {1H} NMR (125 MHz, CDCl3): δ = 30.5, 34.6, 48.9, 72.7, 122.1, 127.1, 129.4, 131.5, 131.6, 135.5, 139.4, 153.8.

HRMS (ES+, Ar): m/z [M + K]+ calcd for C22H26 79Br4OK: 660.8349; found: 660.8337.


#

2,6-Di-tert-butyl-4-(2,2,2-tribromo-1-(2-bromophenyl)ethyl)phenol (3i)

White solid; yield: 442 mg (71%); mp 177–179 °C.

IR (neat): 3622 (s), 2950 (s), 1436 (vs), 1230 (m), 1154 (m), 1022 (m), 751 (s), 733 (s), 712 cm–1 (s).

1H NMR (500 MHz, CDCl3): δ = 1.44 (s, 18 H), 5.25 (s, 1 H), 5.90 (s, 1 H), 7.16 (t, J = 7.9 Hz, 1 H), 7.39 (t, J = 7.9 Hz, 1 H), 7.51 (s, 2 H), 7.60 (d, J = 7.9 Hz, 1 H), 8.40 (d, J = 7.9 Hz, 1 H).

3C {1H} NMR (125 MHz, CDCl3): δ = 30.5, 34.6, 48.2, 70.0, 126.5, 127.4, 127.8, 128.2, 128.2, 129.1, 133.6, 135.2, 140.3, 153.8.

HRMS (ES+, Ar): m/z [M + K]+ calcd for C22H26 79Br4OK: 660.8349; found: 660.8348.


#

2,6-Di-tert-butyl-4-(2,2,2-tribromo-1-(4-chlorophenyl)ethyl)phenol (3j)

Light yellow solid; yield: 451 mg (78%); mp 135–137 °C.

IR (neat): 3633 (s), 2958 (vs), 1490 (w), 1435 (s), 1361 (w), 1321 (w), 1238 (m), 1156 (m), 739 (s), 721 cm–1 (m).

1H NMR (400 MHz, CDCl3): δ = 1.44 (s, 18 H), 5.10 (s, 1 H), 5.24 (s, 1 H), 7.33 (d, J = 8.6 Hz, 2 H), 7.45 (s, 2 H), 7.67 (d, J = 8.6 Hz, 2 H).

13C {1H} NMR (100 MHz, CDCl3): δ = 30.5, 34.6, 49.1, 72.6, 127.1, 128.5, 129.4, 131.2, 133.9, 135.4, 138.8, 153.7.

HRMS (ES+, Ar): m/z [M – HBr]H+ calcd for C22H26 79Br2O35Cl: 499.0033; found: 499.0031.


#

2,6-Di-tert-butyl-4-(2,2,2-tribromo-1-(2-chlorophenyl)ethyl)phenol (3k)

Light yellow solid; yield: 422 mg (73%); mp 162–164 °C.

IR (neat): 3634 (s), 2956 (vs), 2928 (vs), 1464 (s), 1439 (vs), 1361 (w), 1321 (w), 1237 (m), 1157 (m), 1053 (m), 1040 (m), 754 (s), 740 cm–1 (s).

1H NMR (500 MHz, CDCl3): δ = 1.43 (s, 18 H), 5.24 (s, 1 H), 5.89 (s, 1 H), 7.24 (t, J = 7.8 Hz, 1 H), 7.34 (t, J = 7.8 Hz, 1 H), 7.39 (d, J = 7.8 Hz, 1 H), 7.48 (s, 2 H), 8.38 (d, J = 7.8 Hz, 1 H).

13C {1H} NMR (125 MHz, CDCl3): δ = 30.5, 34.6, 48.3, 67.2, 126.7, 127.9, 128.2 (2 C), 128.8, 130.2, 135.0, 135.2, 138.7, 153.8.

HRMS: m/z [M + K]+ calcd for C22H26 79Br3O35ClK: 616.8854; found: 616.8849.


#

2,6-Di-tert-butyl-4-(2,2,2-tribromo-1-(naphthalen-2-yl)ethyl)phenol (3l)

White solid; yield: 410 mg (69%); mp 125–127 °C.

IR (neat): 3631 (s), 3057 (w), 2959 (vs), 2872 (m), 1733 (m), 1599 (w), 1507 (w), 1436 (vs), 1391 (w), 1362 (m), 1321 (m), 1238 (s), 1208 (m), 1155 (s), 1123 (m), 891 (m), 857 (m), 813 (m), 771 (m), 745 (vs), 692 (m), 656 (m), 634 cm–1 (w).

1H NMR (400 MHz, CDCl3): δ = 1.44 (s, 18 H), 5.22 (s, 1 H), 5.31 (s, 1 H), 7.47–7.51 (m, 2 H), 7.57 (s, 2 H), 7.80–7.91 (m, 4 H), 8.19 (s, 1 H).

13C {1H} NMR (100 MHz, CDCl3): δ = 30.5, 34.6, 49.8, 73.5, 126.3, 126.4, 127.3, 127.4, 127.7, 127.8, 128.4, 129.4, 129.8, 132.9, 133.2, 135.4, 137.9, 153.7.

HRMS (ES+, Ar): m/z [M – HBr]H+ calcd for C26H29 79Br2O: 515.0585; found: 515.0573.


#

2,6-Di-tert-butyl-4-(2,2,2-tribromo-1-(naphthalen-1-yl)ethyl)phenol (3m)

Orange solid; yield: 390 mg (66%); mp 158–160 °C.

IR (neat): 3634 (s), 3051 (m), 2953 (vs), 1599 (m), 1510 (m), 1434 (vs), 1399 (s), 1361 (s), 1321 (s), 1240 (vs), 1208 (s), 1156 (vs), 1122 (s), 1025 (m), 891 (s), 859 (m), 809 (s), 776 (vs), 739 (vs), 704 (s), 683 (s), 622 cm–1 (s).

1H NMR (400 MHz, CDCl3): δ = 1.42 (s, 18 H), 5.21 (s, 1 H), 6.09 (s, 1 H), 7.48 (t, J = 7.5 Hz, 1 H), 7.55 (t, J = 8.2 Hz, 1 H), 7.57 (s, 2 H), 7.58 (t, J = 8.2 Hz, 1 H), 7.84 (d, J = 7.5 Hz, 1 H), 7.86 (d, J = 7.5 Hz, 1 H), 8.21 (d, J = 8.2 Hz, 1 H), 8.54 (d, J = 8.2 Hz, 1 H); confirmed by 1H-1H COSY experiment.

13C {1H} NMR (100 MHz, CDCl3): δ = 30.5, 34.5, 49.9, 66.3, 123.1, 124.7, 125.0, 125.6, 126.6, 128.2, 128.5, 128.6, 129.4, 131.9, 134.2, 135.0, 136.8, 153.7.

HRMS (ES+, Ar): m/z [M – HBr]H+ calcd for C26H29 79Br2O: 515.0585; found: 515.0602.


#

2,6-Di-tert-butyl-4-(2,2,2-tribromo-1-(thiophen-2-yl)ethyl)phenol (3n)

White solid; yield: 351 mg (64%); mp 146–148 °C.

IR (neat): 3627 (s), 3108 (w), 2958 (vs), 2871 (s), 1662 (w), 1587 (w), 1435 (vs), 1361 (s), 1317 (m), 1286 (m), 1263 (s), 1236 (s), 1210 (s), 1152 (s), 1123 (s), 1046 (w), 947 (w), 891 (m), 882 (m), 839 (m), 809 (m), 771 (m), 735 (s), 706 (s), 678 (m), 630 cm–1 (m).

1H NMR (400 MHz, CDCl3): δ = 1.45 (s, 18 H), 5.26 (s, 1 H), 5.41 (s, 1 H), 6.99 (t, J = 3.6 Hz, 1 H), 7.29–7.32 (m, 2 H), 7.57 (s, 2 H).

13C {1H} NMR (100 MHz, CDCl3): δ = 30.5, 34.6, 51.6, 69.5, 125.8, 126.0, 127.8, 128.8, 129.1, 135.3, 141.8, 153.9.

HRMS (ES+, Ar): m/z [M + H]+ calcd for C20H26 79Br3OS: 550.9254; found: 550.9269.


#

(E)-2,6-Di-tert-butyl-4-(1,1,1-tribromo-4-phenylbut-3-en-2-yl)phenol (3o)

White solid; yield: 290 mg (51%); mp 130–132 °C.

IR (neat): 3632 (vs), 3081 (m), 2949 (vs), 1646 (w), 1598 (m), 1578 (w), 1441 (vs), 1391 (s), 1361 (s), 1322 (s), 1284 (m), 1238 (vs), 1217 (vs), 1156 (s), 1123 (m), 1071 (w), 1027 (m), 961 (s), 908 (s), 882 (s), 797 (s), 747 (vs), 641 (m), 626 cm–1 (s).

1H NMR (500 MHz, CDCl3): δ = 1.47 (s, 18 H), 4.47 (d, J = 5.6 Hz, 1 H), 5.27 (s, 1 H), 6.68, 6.72 (ABq, J = 15.8 Hz, 2 H), 7.27 (t, J = 7.5 Hz, 1 H), 7.34 (t, J = 7.5 Hz, 2 H), 7.39 (s, 2 H), 7.45 (d, J = 7.5 Hz, 2 H).

13C {1H} NMR (125 MHz, CDCl3): δ = 30.6, 34.6, 53.7, 70.9, 126.8, 127.1, 127.8, 128.1, 128.8, 129.4, 135.1, 135.4, 136.9, 154.0.

HRMS (ES+, Ar): m/z [M – HBr]H+ calcd for C24H29 79Br2O: 491.0585; found: 491.0580.


#

2,6-Diisopropyl-4-(2,2,2-tribromo-1-phenylethyl)phenol (3q)

White solid; yield: 363 mg (70%); mp 118–120 °C.

IR (neat): 3591 (s), 2960 (vs), 1600 (w), 1491 (m), 1470 (s), 1452 (s), 1285 (s), 1201 (s), 1153 (m), 765 (w), 698 (vs), 624 cm–1 (w).

1H NMR (500 MHz, CDCl3): δ = 1.28 (d, J = 6.5 Hz, 12 H), 3.15 (septet, J = 6.5 Hz, 2 H), 4.82 (s, 1 H), 5.17 (s, 1 H), 7.33 (t, J = 7.3 Hz, 1 H), 7.37 (t, J = 7.3 Hz, 2 H), 7.40 (s, 2 H), 7.75 (d, J = 7.3 Hz, 2 H).

13C {1H} NMR (125 MHz, CDCl3): δ = 23.0, 27.4, 49.5, 73.2, 125.8, 127.9, 128.3, 129.9, 131.2, 133.2, 140.2, 149.9.

HRMS (ES+, Ar): m/z [M + H]+ calcd for C20H23 79Br2 81BrO: 518.9341; found: 518.9341.


#

(Z)-N-(2-Benzylidene-3-(tribromomethyl)-2,3-dihydrobenzofuran-3-yl)-4-methylbenzenesulfonamide (5a)

Yellow solid; yield: 34 mg (27%); mp 172–175 °C.

IR (neat): 3248 (br, m), 2926 (vs), 1596 (s), 1466 (s), 1408 (m), 1337 (vs), 1241 (m), 1164 (vs), 1089 (vs), 900 (m), 753 (vs), 697 cm–1 (m).

1H NMR (CDCl3, 400 MHz): δ = 2.23 (s, 3 H), 6.08 (s, 1 H), 6.09 (s, 1 H), 6.99 (overlapped t, J = 7.7 Hz, 1 H), 7.00 (d, J = 8.0 Hz, 2 H), 7.06 (d, J = 7.7 Hz, 1 H), 7.26 (t, J = 7.2 Hz, 1 H), 7.34 (overlapped d, J = 8.0 Hz, 2 H), 7.35 (overlapped t, J = 7.2 Hz, 2 H), 7.45 (t, J = 7.7 Hz, 1 H), 7.52 (d, J = 7.2 Hz, 2 H), 7.71 (d, J = 7.7 Hz, 1 H).

13C {1H} NMR (CDCl3, 100 MHz): δ = 21.6, 54.9, 76.6, 110.3, 110.7, 121.1, 121.6, 127.6, 127.7, 128.4, 129.2, 129.5 (2 C), 132.3, 133.6, 137.1, 144.0, 150.0, 158.5.

HRMS (ES+, Ar): m/z [M + Na]+ calcd for C23H18 79Br3NO3SNa: 647.8450; found: 647.8449.


#

4-Methyl-N-(2-(2,2,2-tribromo-1-phenylethyl)benzofuran-3-yl)benzenesulfonamide (6a)

Yellow solid; yield: 60 mg (48%); mp 185–188 °C.

IR (neat): 3242 (br, m), 2925 (m), 1618 (br, w), 1453 (m), 1184 (m), 1164 (vs), 1137 (m), 749 (s), 704 cm–1 (m).

1H NMR (CDCl3, 500 MHz): δ = 2.36 (s, 3 H), 5.48 (s, 1 H), 6.54 (br s, 1 H), 7.12 (overlapped d, J = 7.9 Hz, 2 H), 7.10–7.14 (overlapped m, 2 H), 7.29 (t, J = 7.9 Hz, 1 H), 7.34 (t, J = 7.4 Hz, 2 H), 7.38 (d, J = 7.4 Hz, 1 H), 7.51 (d, J = 7.9 Hz, 1 H), 7.55 (d, J = 7.9 Hz, 2 H), 7.74 (d, J = 7.4 Hz, 2 H).

13C {1H} NMR (CDCl3, 100 MHz): δ = 21.8, 44.8, 63.4, 112.1, 116.6, 119.7, 123.6, 125.1, 125.6, 127.6, 128.0, 128.8, 130.0, 131.5, 135.2, 136.4, 144.3, 151.4, 153.6.

HRMS (ES+, Ar): m/z [M + K]+ calcd for C23H18 79Br3NO3SK: 663.8189; found: 663.8196.


#

(Z)-N-(2-(4-Bromobenzylidene)-3-(tribromomethyl)-2,3-dihydrobenzofuran-3-yl)-4-methylbenzenesulfonamide (5b)

Yellow solid; yield: 42 mg (30%); mp 180–183 °C.

IR (neat): 3214 (br, m), 2920 (vs), 1620 (m), 1476 (m), 1336 (s), 1164 (vs), 1086 (w), 902 (s), 754 cm–1 (m).

1H NMR (CDCl3, 400 MHz): δ = 2.27 (s, 3 H), 5.93 (s, 1 H), 6.02 (s, 1 H), 6.97 (t, J = 8.2 Hz, 1 H), 7.03 (d, J = 8.1 Hz, 2 H), 7.06 (d, J = 8.2 Hz, 1 H), 7.33 (d, J = 8.1 Hz, 2 H), 7.39, 7.46 (ABq, J = 8.4 Hz, 4 H), 7.44 (overlapped t, J = 8.2 Hz, 1 H), 7.62 (d, J = 8.2 Hz, 1 H); N–H confirmed by D2O experiment.

13C {1H} NMR (CDCl3, 125 MHz): δ = 21.6, 54.3, 76.6, 109.5, 110.5, 121.1, 121.5, 121.8, 127.7, 129.1, 129.6, 131.0, 131.6, 132.4, 132.5, 137.3, 144.1, 150.9, 158.4.

HRMS (ES+, Ar): m/z [M + K]+ calcd for C23H17 79Br4NO3SK: 741.7294; found: 741.7294.


#

4-Methyl-N-(2-(2,2,2-tribromo-1-(4-bromophenyl)ethyl)benzofuran-3-yl)benzenesulfonamide (6b)

Yellow solid; yield: 76 mg (54%); mp 204–206 °C.

IR (neat): 3252 (br, m), 2924 (w), 2852 (w), 1602 (m), 1509 (m), 1233 (m), 1163 (vs), 1091 (m), 748 (s), 736 (s), 666 cm–1 (m).

1H NMR (CDCl3, 400 MHz): δ = 2.37 (s, 3 H), 5.54 (s, 1 H), 6.51 (s, 1 H), 7.01 (d, J = 7.8 Hz, 1 H), 7.08 (overlapped t, J = 7.8 Hz, 1 H), 7.10 (d, J = 8.5 Hz, 2 H), 7.29 (t, J = 7.8 Hz, 1 H), 7.50 (overlapped d, J = 7.8 Hz, 1 H), 7.49, 7.51 (ABq, J = 8.4 Hz, 4 H), 7.68 (d, J = 8.5 Hz, 2 H); N–H confirmed by D2O experiment.

13C {1H} NMR (CDCl3, 100 MHz): δ = 21.8, 44.0, 62.7, 112.1, 116.9, 119.5, 123.4, 123.7, 124.9, 125.7, 127.6, 129.9, 131.3, 133.2, 134.2, 136.4, 144.5, 151.1, 153.6.

HRMS (ES+, Ar): m/z [M + K]+ calcd for C23H17 79Br4NO3SK: 741.7294; found: 741.7293.


#

(Z)-N-(2-(4-Fluorobenzylidene)-3-(tribromomethyl)-2,3-dihydrobenzofuran-3-yl)-4-methylbenzenesulfonamide (5c)

Yellow solid; yield: 36 mg (28%); mp 185–188 °C.

IR (neat): 3240 (br, m), 2925 (vs), 1598 (s), 1336 (vs), 1233 (s), 1162 (vs), 1087 (s), 878 (m), 754 cm–1 (vs).

1H NMR (CDCl3, 400 MHz): δ = 2.27 (s, 3 H), 5.99 (s, 1 H), 6.06 (s, 1 H), 6.96 (t, J = 7.5 Hz, 1 H), 7.02 (overlapped d, J = 7.6 Hz, 2 H), 7.03–7.06 (unresolved m, 3 H), 7.33 (d, J = 7.6 Hz, 2 H), 7.44 (t, J = 7.5 Hz, 1 H), 7.51 (unresolved dd, 2 H), 7.63 (d, J = 7.5 Hz, 1 H); confirmed by 1H-1H COSY experiment.

13C {1H} NMR (CDCl3, 100 MHz): δ = 21.6, 54.8, 76.6, 109.6, 110.4, 115.4 (d, J = 21.3 Hz), 121.1, 121.7, 127.7, 129.1, 129.5, 129.8 (d, J = 2.5 Hz), 131.2 (d, J = 7.9 Hz), 132.3, 137.3, 144.0, 149.9, 158.5, 162.0 (d, J = 246.5 Hz).

19F NMR (CDCl3, 470 MHz): δ = –113.4.

HRMS (ES+, Ar): m/z [M + Na]+ calcd for C23H17 79Br3 19FNO3SNa: 665.8356; found: 665.8358.


#

4-Methyl-N-(2-(2,2,2-tribromo-1-(4-fluorophenyl)ethyl)benzofuran-3-yl)benzenesulfonamide (6c)

Yellow solid; yield: 67 mg (52%); mp 213–215 °C.

IR (neat): 3235 (br, m), 2925 (s), 1602 (w), 1509 (w), 1453 (w), 1340 (m), 1324 (m), 1229 (w), 1198 (w), 1162 (vs), 1138 (s), 750 (m), 736 cm–1 (m).

1H NMR (CDCl3, 400 MHz): δ = 2.36 (s, 3 H), 5.60 (s, 1 H), 6.78 (s, 1 H), 7.04 (overlapped d, J = 8.4 Hz, 1 H), 7.05–7.10 (overlapped m, 3 H), 7.10 (d, J = 8.0 Hz, 2 H), 7.29 (t, J = 8.4 Hz, 1 H), 7.51 (d, J = 8.4 Hz, 1 H), 7.54 (d, J = 8.0 Hz, 2 H), 7.81 (dd, J = 7.3, 5.6 Hz, 2 H); confirmed by 1H-1H COSY experiment.

13C {1H} NMR (CDCl3, 100 MHz): δ = 21.7, 44.9, 62.4, 112.1, 115.0 (d, J = 21.2 Hz), 116.8, 119.6, 123.6, 124.9, 125.6, 127.6, 129.9, 131.1 (d, J = 3.2 Hz), 133.5 (d, J = 8.2 Hz), 136.3, 144.4, 151.2, 153.6, 163.0 (d, J = 247.4 Hz).

19F NMR (CDCl3, 470 MHz): δ = –112.6.

HRMS (ES+, Ar): m/z [M + Na]+ calcd for C23H17 79Br3 19FNO3SNa: 665.8356; found: 665.8360.


#

(Z)-N-(2-(4-Chlorobenzylidene)-3-(tribromomethyl)-2,3-dihydrobenzofuran-3-yl)-4-methylbenzenesulfonamide (5d)

Yellow solid; yield: 40 mg (30%); mp 201–204 °C.

IR (neat): 3258 (br, m), 2927 (vs), 1596 (w), 1337 (s), 1164 (vs), 1086 (m), 753 cm–1 (w).

1H NMR (CDCl3, 400 MHz): δ = 2.27 (s, 3 H), 6.00 (s, 1 H), 6.05 (s, 1 H), 6.97 (t, J = 7.9 Hz, 1 H), 7.03 (d, J = 8.0 Hz, 2 H), 7.06 (d, J = 7.9 Hz, 1 H), 7.31 (d, J = 8.1 Hz, 2 H), 7.33 (d, J = 8.0 Hz, 2 H), 7.44 (overlapped t, J = 7.9 Hz, 1 H), 7.46 (d, J = 8.1 Hz, 2 H), 7.63 (d, J = 7.9 Hz, 1 H).

13C {1H} NMR (CDCl3, 100 MHz): δ = 21.6, 54.5, 76.6, 109.5, 110.4, 121.1, 121.8, 127.7, 128.6, 129.0, 129.6, 130.7, 132.1, 132.4, 133.2, 137.3, 144.0, 150.7, 158.4.

HRMS (ES+, Ar): m/z [M + Na]+ calcd for C23H17 79Br3 35ClNO3SNa: 681.8060; found: 681.8059.


#

4-Methyl-N-(2-(2,2,2-tribromo-1-(4-chlorophenyl)ethyl)benzofuran-3-yl)benzenesulfonamide (6d)

Yellow solid; yield: 67 mg (51%); mp 193–195 °C.

IR (neat): 3246 (br, s), 3053 (vw), 2923 (vw), 1596 (vw), 1451 (vw), 1327 (vw), 1163 (vs), 1136 (m), 1092 (s), 750 (vvs), 667 cm–1 (s).

1H NMR (CDCl3, 400 MHz): δ = 2.37 (s, 3 H), 5.53 (s, 1 H), 6.38 (s, 1 H), 7.00 (d, J = 7.9 Hz, 1 H), 7.08 (t, J = 7.9 Hz, 1 H), 7.11 (d, J = 8.0 Hz, 2 H), 7.28 (t, J = 7.9 Hz, 1 H), 7.33 (d, J = 8.5 Hz, 2 H), 7.51 (d, J = 8.0 Hz, 2 H), 7.51 (overlapped d, J = 7.9 Hz, 1 H), 7.73 (d, J = 8.5 Hz, 2 H).

13C {1H} NMR (CDCl3, 100 MHz): δ = 21.7, 44.2, 62.6, 112.1, 116.8, 119.5, 123.7, 124.9, 125.7, 127.6, 128.3, 129.9, 132.9, 133.7, 135.1, 136.4, 144.5, 151.3, 153.6.

HRMS (ES+, Ar): m/z [M + Na]+ calcd for C23H17 79Br3 35ClNO3SNa: 681.8060; found: 681.8058.


#

(Z)-N-(2-(2-Chlorobenzylidene)-3-(tribromomethyl)-2,3-dihydrobenzofuran-3-yl)-4-methylbenzenesulfonamide (5e)

Yellow solid; yield: 26 mg (20%); mp 206–208 °C.

IR (neat): 3242 (br, w), 2925 (w), 1611 (w), 1596 (m), 1475 (m), 1466 (m), 1404 (m), 1339 (s), 1241 (m), 1166 (s), 1087 (s), 900 (m), 752 cm–1 (s).

1H NMR (CDCl3, 400 MHz): δ = 2.20 (s, 3 H), 5.98 (s, 1 H), 6.57 (s, 1 H), 7.00 (d, J = 8.1 Hz, 2 H), 7.03 (overlapped t, J = 7.7 Hz, 1 H), 7.05 (d, J = 7.7 Hz, 1 H), 7.18 (t, J = 7.6 Hz, 1 H), 7.28 (overlapped t, J = 7.6 Hz, 1 H), 7.31 (d, J = 8.1 Hz, 2 H), 7.37 (d, J = 7.6 Hz, 1 H), 7.46 (t, J = 7.7 Hz, 1 H), 7.73 (d, J = 7.7 Hz, 1 H), 8.01 (d, J = 7.6 Hz, 1 H).

13C {1H} NMR (CDCl3, 100 MHz): δ = 21.6, 54.1, 76.5, 105.7, 110.3, 120.8, 121.8, 126.8, 127.7, 128.6, 129.5 (merged, 2 C), 129.6, 130.6, 131.7, 132.5, 133.5, 136.9, 144.2, 152.0, 158.4.

HRMS (ES+, Ar): m/z [M + Na]+ calcd for C23H17 79Br3 35ClNO3SNa: 681.8060; found: 681.8058.


#

4-Methyl-N-(2-(2,2,2-tribromo-1-(2-chlorophenyl)ethyl)benzofuran-3-yl)benzenesulfonamide (6e)

Yellow solid; yield: 55 mg (42%); mp 197–199 °C.

IR (neat): 3234 (br, m), 2942 (vw), 2845 (vw), 1598 (w), 1451 (w), 1327 (m), 1165 (s), 888 (m), 813 (m), 741 (vs), 705 (m), 673 cm–1 (w).

1H NMR (CDCl3, 400 MHz): δ = 2.38 (s, 3 H), 6.26 (s, 1 H), 6.34 (s, 1 H), 7.14 (overlapped t, J = 8.0 Hz, 1 H), 7.15 (overlapped d, J = 7.9 Hz, 2 H), 7.25 (d, J = 8.0 Hz, 1 H), 7.30–7.32 (m, 3 H), 7.41 (br dd, J = 5.4, 3.6 Hz, 1 H), 7.52 (d, J = 8.0 Hz, 1 H), 7.65 (d, J = 7.9 Hz, 2 H), 8.41 (br dd, J = 5.4, 3.6 Hz, 1 H).

13C {1H} NMR (CDCl3, 100 MHz): δ = 21.7, 41.8, 57.1, 112.0, 117.3, 120.6, 123.7, 124.9, 125.7, 126.7, 127.7, 129.9, 130.1 (2 C), 131.8, 133.2, 135.8, 136.9, 144.3, 150.3, 153.6.

HRMS (ES+, Ar): m/z [M + K]+ calcd for C23H17 79Br3 35ClNO3SK: 697.7799; found: 697.7800.


#

(Z)-N-(2-(3-Methoxybenzylidene)-3-(tribromomethyl)-2,3-dihydrobenzofuran-3-yl)-4-methylbenzenesulfonamide (5f)

Yellow solid; yield: 29 mg (22%); mp 176–179 °C.

IR (neat): 3412 (br, s), 2921 (m), 1597 (m), 1464 (s), 1336 (s), 1264 (m), 1163 (vs), 1090 (s), 738 cm–1 (s).

1H NMR (CDCl3, 500 MHz): δ = 2.26 (s, 3 H), 3.85 (s, 3 H), 5.93 (s, 1 H), 6.03 (s, 1 H), 6.83 (d, J = 7.9 Hz, 1 H), 6.97 (t, J = 7.6 Hz, 1 H), 7.02 (d, J = 7.7 Hz, 2 H), 7.05 (d, J = 7.9 Hz, 1 H), 7.08 (d, J = 7.6 Hz, 1 H), 7.11 (s, 1 H), 7.26 (t, J = 7.9 Hz, 1 H), 7.33 (d, J = 7.7 Hz, 2 H), 7.44 (t, J = 7.6 Hz, 1 H), 7.66 (d, J = 7.6 Hz, 1 H).

13C {1H} NMR (CDCl3, 125 MHz): δ = 21.6, 54.8, 55.4, 76.6, 110.4, 110.7, 113.2, 115.0, 121.1, 121.7, 122.3, 127.7, 129.1, 129.4, 129.6, 132.3, 134.8, 137.3, 144.1, 150.3, 158.6, 159.7.

HRMS (ES+, Ar): m/z [M + K]+ calcd for C24H20 79Br3NO4SK: 693.8295; found: 693.8291.


#

4-Methyl-N-(2-(2,2,2-tribromo-1-(3-methoxyphenyl)ethyl)benzofuran-3-yl)benzenesulfonamide (6f)

Yellow solid; yield: 56 mg (42%); mp 158–161 °C.

IR (neat): 3233 (br, m), 2922 (br, vs), 2856 (s), 1600 (s), 1453 (m), 1264 (w), 1164 (s), 751 cm–1 (s).

1H NMR (CDCl3, 500 MHz): δ = 2.35 (s, 3 H), 3.85 (s, 3 H), 5.50 (s, 1 H), 6.72 (s, 1 H), 6.93 (d, J = 7.6 Hz, 1 H), 7.10–7.18 (overlapped m, 2 H), 7.09 (overlapped d, J = 7.5 Hz, 2 H), 7.25–7.27 (m, 2 H), 7.31 (t, J = 7.6 Hz, 1 H), 7.40 (s, 1 H), 7.50 (d, J = 7.6 Hz, 1 H), 7.57 (d, J = 7.5 Hz, 2 H).

13C {1H} NMR (CDCl3, 125 MHz): δ = 21.7, 44.4, 55.5, 63.2, 112.1, 113.8, 116.7, 117.7, 119.7, 123.6, 124.0, 125.0, 125.5, 127.6, 128.8, 129.9, 136.4, 136.5, 144.4, 151.2, 153.6, 159.0.

HRMS (ES+, Ar): m/z [M + Na]+ calcd for C24H20 79Br3NO4SNa: 677.8555; found: 677.8556.


#

(Z)-4-Methyl-N-(2-(4-methylbenzylidene)-3-(tribromomethyl)-2,3-dihydrobenzofuran-3-yl)benzenesulfonamide (5g)

Yellow solid; yield: 32 mg (25%); mp 178–180 °C.

IR (neat): 3243 (br, m), 2924 (vs), 1596 (w), 1474 (w), 1465 (w), 1337 (s), 1242 (m), 1164 (s), 810 cm–1 (w).

1H NMR (CDCl3, 400 MHz): δ = 2.25 (s, 3 H), 2.36 (s, 3 H), 5.91 (s, 1 H), 6.02 (s, 1 H), 6.97 (t, J = 7.9 Hz, 1 H), 7.01 (d, J = 8.1 Hz, 2 H), 7.05 (d, J = 7.9 Hz, 1 H), 7.15 (d, J = 8.0 Hz, 2 H), 7.33 (d, J = 8.1 Hz, 2 H), 7.40 (d, J = 8.0 Hz, 2 H), 7.44 (t, J = 7.9 Hz, 1 H), 7.68 (d, 7.9 Hz, 1 H); confirmed by 1H-1H COSY experiment.

13C {1H} NMR (CDCl3, 100 MHz): δ = 21.5, 21.6, 55.3, 76.6, 110.4, 110.8, 121.3, 121.6, 127.7, 129.1, 129.2, 129.5, 129.6, 130.8, 132.3, 137.3, 137.6, 144.0, 149.3, 158.6.

HRMS (ES+, Ar): m/z [M + K]+ calcd for C24H20 79Br3NO3SK: 677.8346; found: 677.8343.


#

4-Methyl-N-(2-(2,2,2-tribromo-1-(p-tolyl)ethyl)benzofuran-3-yl)benzenesulfonamide (6g)

Yellow solid; yield: 54 mg (43%); mp 169–171 °C.

IR (neat): 3253 (br, s), 2922 (s), 1597 (w), 1452 (w), 1325 (m), 1199 (m), 1164 (vs), 1135 (m), 1092 (m), 814 (s), 748 (s), 732 (s), 668 (m), 563 cm–1.

1H NMR (CDCl3, 500 MHz): δ = 2.36 (s, 3 H), 2.38 (s, 3 H), 5.40 (s, 1 H), 6.30 (s, 1 H), 7.08–7.10 (m, 2 H), 7.13 (d, J = 8.1 Hz, 2 H), 7.15 (d, J = 8.2 Hz, 2 H), 7.29 (ddd, J = 8.3, 5.4, 2.9 Hz, 1 H), 7.51 (d, J = 8.3 Hz, 1 H), 7.55 (d, J = 8.2 Hz, 2 H), 7.61 (d, J = 8.1 Hz, 2 H).

13C {1H} NMR (CDCl3, 100 MHz): δ = 21.5, 21.8, 45.4, 63.2, 112.1, 116.4, 119.6, 123.6, 125.1, 125.5, 127.6, 128.8, 130.0, 131.4, 132.3, 136.6, 138.8, 144.3, 151.8, 153.6.

HRMS (ES+, Ar): m/z [M + K]+ calcd for C24H20 79Br3NO3SK: 677.8346; found: 677.8350.


#

4-Methyl-N-(2-(2,2,2-tribromo-1-(4-methoxyphenyl)ethyl)benzofuran-3-yl)benzenesulfonamide (6h)

Yellow solid; yield: 59 mg (45%); mp 174–176 °C.

IR (neat): 3234 (br, s), 2930 (s), 1607 (s), 1512 (w), 1453 (w), 1255 (vs), 1164 (vs), 1091 (w), 1035 (m), 749 (s), 738 cm–1 (s).

1H NMR (CDCl3, 500 MHz): δ = 2.37 (s, 3 H), 3.82 (s, 3 H), 5.43 (s, 1 H), 6.52 (s, 1 H), 6.87 (d, J = 8.7 Hz, 2 H), 7.09–7.10 (overlapped m, 2 H), 7.11 (overlapped d, J = 8.2 Hz, 2 H), 7.28 (td, J = 8.3, 4.2 Hz, 1 H), 7.51 (d, J = 8.3 Hz, 1 H), 7.55 (d, J = 8.2 Hz, 2 H), 7.67 (d, J = 8.7 Hz, 2 H).

13C {1H} NMR (CDCl3, 125 MHz): δ = 21.7, 46.3, 55.4, 62.7, 112.0, 113.3, 116.3, 119.6, 123.6, 125.1, 125.5, 127.3, 127.6, 130.0, 132.8, 136.5, 144.3, 151.8, 153.6, 159.9.

HRMS (ES+, Ar): m/z [M + K]+ calcd for C24H20 79Br3NO4SK: 693.8295; found: 693.8293.


#

(Z)-4-Methyl-N-(2-(naphthalen-1-ylmethylene)-3-(tribromometh­yl)-2,3-dihydrobenzofuran-3-yl)benzenesulfonamide (5i)

Yellow solid; yield: 30 mg (22%); mp 132–135 °C.

IR (neat): 3252 (br, w), 3061 (vw), 2922 (s), 1613 (m), 1596 (m), 1465 (m), 1336 (s), 1241 (w), 1164 (vs), 1092 cm–1 (s).

1H NMR (CDCl3, 400 MHz): δ = 2.14 (s, 3 H), 6.22 (s, 1 H), 6.92 (overlapped d, J = 8.1 Hz, 2 H), 6.94 (overlapped s, 1 H), 6.94 (overlapped t, J = 7.7 Hz, 1 H), 7.02 (d, J = 7.9 Hz, 1 H), 7.38 (d, J = 8.1 Hz, 2 H), 7.43 (t, J = 7.9 Hz, 1 H), 7.49 (d, J = 6.2 Hz, 1 H), 7.50 (d, J = 6.2 Hz, 1 H), 7.53 (t, J = 7.7 Hz, 1 H), 7.62 (d, J = 7.7 Hz, 1 H), 7.81 (d, J = 7.7 Hz, 1 H), 7.86 (t, J = 6.2 Hz, 1 H), 7.97 (t, J = 6.2 Hz, 1 H), 7.99 (d, J = 7.7 Hz, 1 H); confirmed by 1H-1H COSY experiment.

13C {1H} NMR (CDCl3, 100 MHz): δ = 21.5, 55.1, 76.5, 106.9, 110.5, 121.2, 121.5, 124.3, 125.6, 125.8, 126.4, 127.7, 127.8, 128.2, 128.7, 129.0, 129.5, 130.0, 131.6, 132.3, 133.8, 137.3, 144.0, 151.7, 158.6.

HRMS (ES+, Ar): m/z [M + Na]+ calcd for C27H20 79Br3NO3SNa: 697.8606; found: 697.8606.


#

4-Methyl-N-(2-(2,2,2-tribromo-1-(naphthalen-1-yl)ethyl)benzofuran-3-yl)benzenesulfonamide (6i)

Yellow solid; yield: 54 mg (40%); mp 149–151 °C.

IR (neat): 3254 (br, m), 2925 (vs), 2857 (m), 1612 (w), 1598 (w), 1451 (w), 1327 (w), 1163 (s), 1092 (w), 776 (s), 754 cm–1 (vs).

1H NMR (CDCl3, 400 MHz): δ = 2.24 (s, 3 H), 6.28 (s, 1 H), 6.65 (s, 1 H), 6.94 (d, J = 7.7 Hz, 2 H), 7.10 (overlapped d, J = 7.0 Hz, 1 H), 7.11 (overlapped t, J = 7.0 Hz, 1 H), 7.31 (t, J = 7.0 Hz, 1 H), 7.50 (overlapped d, J = 7.7 Hz, 2 H), 7.51 (overlapped d, J = 7.5 Hz, 1 H), 7.56–7.63 (overlapped m, 2 H), 7.60 (overlapped d, J = 7.0 Hz, 1 H), 7.88 (2 × t, J = 7.5 Hz, 2 H), 8.32 (d, J = 8.5 Hz, 1 H), 8.53 (d, J = 7.5 Hz, 1 H); confirmed by 1H-1H COSY experiment.

13C {1H} NMR (CDCl3, 100 MHz): δ = 21.7, 43.8, 55.7, 112.1, 116.5, 119.9, 123.7, 124.6, 124.9, 125.1, 125.5, 126.0, 126.6, 127.5, 129.1, 129.5, 129.7, 129.8, 131.6, 132.2, 134.1, 136.5, 144.1, 152.2, 153.6.

HRMS (ES+, Ar): m/z [M + K]+ calcd for C27H20 79Br3NO3SK: 713.8346; found: 713.8340.


#

(Z)-N-(2-Benzylidene-5-bromo-3-(tribromomethyl)-2,3-dihydrobenzofuran-3-yl)-4-methylbenzenesulfonamide (5j)

Yellow solid; yield: 58 mg (41%); mp 195–197 °C.

IR (neat): 3243 (m), 2925 (m), 1467 (m), 1338 (s), 1163 (vs), 1094 (s), 901 (m), 813 cm–1 (m).

1H NMR (CDCl3, 400 MHz): δ = 2.34 (s, 3 H), 5.97 (s, 1 H), 6.27 (s, 1 H), 6.98 (d, J = 8.6 Hz, 1 H), 7.13 (d, J = 8.1 Hz, 2 H), 7.28 (t, J = 7.5 Hz, 1 H), 7.31 (d, J = 1.7 Hz, 1 H), 7.37 (t, J = 7.5 Hz, 2 H), 7.41 (d, J = 8.1 Hz, 2 H), 7.50 (dd, J = 8.6, 1.7 Hz, 1 H), 7.60 (d, J = 7.4 Hz, 2 H).

13C {1H} NMR (CDCl3, 100 MHz): δ = 21.8, 53.7, 76.3, 111.3, 112.1, 113.7, 123.1, 127.6, 127.9, 128.6, 129.6, 129.8, 131.3, 133.4, 135.1, 137.4, 144.4, 150.5, 157.7.

HRMS (ES+, Ar): m/z [M + K]+ calcd for C23H17 79Br4NO3SK: 741.7294; found: 741.7294.


#

2,6-Di-tert-butyl-4-(2,2-dibromo-1-(2-hydroxyphenyl)vinyl)phenol (7)

To a stirred solution of tribromo compound 3f (337 mg, 0.5 mmol) in THF (5 mL) was added TBAF (33.0 mg, 0.6 mmol, 1.0 equiv) under N2 at rt. After completion of the reaction (monitored by TLC), the mixture was directly subjected to column chromatography (silica gel, PE/EtOAc, 90:10, gradient elution) to afford pure product 7 as a yellow sticky liquid; yield: 201 mg (83%).

IR (neat): 3628 (s), 3399 (br vs), 2956 (m), 2872 (w), 1653 (m), 1448 (m), 1435 (m), 1237 (w), 1154 (w), 1019 (m), 753 cm–1 (m).

1H NMR (500 MHz, CDCl3): δ = 1.39 (s, 18 H), 5.33 (br s, 1 H), 6.91 (dd, J = 7.7 Hz, 1 H), 6.94 (t, J = 7.7 Hz, 1 H), 7.16 (d, J = 7.7 Hz, 1 H), 7.21 (s, 2 H), 7.24 (t, J = 7.7 Hz, 1 H), 7.26 (br s, 1 H).

13C {1H} NMR (125 MHz, CDCl3): δ = 30.4, 34.6, 91.2, 116.5, 121.0, 126.0, 129.3, 129.8, 130.0, 130.2, 135.8, 144.0, 151.8, 154.2.

HRMS (ES+, Ar): m/z [M + H]+ calcd for C22H26 79Br2O2: 481.0378; found: 481.0374.


#

N-(2-(2,2-Dibromo-1-(3-methoxyphenyl)vinyl)benzofuran-3-yl)-4-methylbenzenesulfonamide (8)

To a stirred solution of tribromo compound 6f (65 mg, 0.1 mmol) in MeOH (2 mL) was added KOH (17 mg, 0.3 mmol, 3.0 equiv) under N2 at rt. After completion of the reaction (3 h, monitored by TLC), the solvent was evaporated under reduced pressure, the residue was treated with water (10 mL) and EtOAc (10 mL). The layers were separated and the aqueous layer was further extracted with EtOAc (3 × 10 mL). The combined organic layers were dried (anhyd Na2SO4) and concentrated in vacuo to afford the crude product, which was purified by column chromatography (silica gel, PE/EtOAc, 90:10, gradient elution) to give 8 as a yellow liquid; yield: 45 mg (78%).

IR (neat): 3250 (m), 2931 (w), 2837 (vw), 1597 (s), 1165 (vs), 1091 (m), 752 cm–1 (s).

1H NMR (400 MHz, CDCl3): δ = 2.41 (s, 3 H), 3.78 (s, 3 H), 5.81 (s, 1 H), 6.40 (dd, J = 8.0, 2.0 Hz, 1 H), 6.52 (d, J = 2.0 Hz, 1 H), 6.88 (dd, J = 8.0, 2.0 Hz, 1 H), 7.18 (t, J = 8.0 Hz, 1 H), 7.25 (t, J = 7.5 Hz, 1 H), 7.28 (d, J = 8.1 Hz, 2 H), 7.33 (t, J = 7.5 Hz, 1 H), 7.38 (d, J = 7.5 Hz, 1 H), 7.65 (d, J = 8.1 Hz, 2 H), 7.66 (d, J = 7.5 Hz, 1 H).

13C {1H} NMR (100 MHz, CDCl3): δ = 21.7, 55.5, 95.8, 111.7, 114.4, 115.2, 116.6, 121.2, 121.4, 123.7, 125.9, 126.2, 127.7, 129.7, 130.0, 136.1, 136.2, 138.7, 144.4, 148.3, 153.7, 159.6.

HRMS (ES+, Ar): m/z [M + H]+ calcd for C24H19 79Br81BrNO4S: 577.9426; found: 577.9426.


#

2-tert-Butyl-4-(2,2,2-tribromo-1-(2-chlorophenyl)ethyl)phenol (9); Procedure for the De-tert-butylation of CBr3 Adducts

To a stirred solution of tribromo compound 3k (58 mg, 0.1 mmol) in dry toluene (3 mL), anhyd AlCl3 (1.0 mmol, 10 equiv) was added at 0 °C under N2, and the mixture was stirred at rt. After the completion of the reaction (monitored by TLC) the reaction was quenched with water (2 mL). The product was extracted with EtOAc (3 × 10 mL) and the combined organic layers were washed with brine (10 mL) and dried (anhyd Na2SO4). Then, the solvent was evaporated under reduced pressure and the crude residue was purified by column chromatography (silica gel, PE/EtOAc, 95:5) to give 9 as a yellow liquid; yield: 46 mg (87%).

IR (neat): 3558 (s), 2956 (vs), 1604 (m), 1504 (m), 1420 (m), 1259 (s), 1180 (m), 1085 (m), 1038 (m), 907 (w), 813 (s), 738 cm–1 (vs).

1H NMR (400 MHz, CDCl3): δ = 1.40 (s, 9 H), 4.95 (s, 1 H), 5.89 (s, 1 H), 6.61 (d, J = 8.3 Hz, 1 H), 7.24 (td, J = 8.0, 1.5 Hz, 1 H), 7.35 (td, J = 8.0, 1.5 Hz, 1 H), 7.36 (dd, J = 8.3, 2.3 Hz, 1 H), 7.38 (dd, J = 8.0, 1.5 Hz, 1 H), 7.60 (d, J = 2.3 Hz, 1 H), 8.37 (dd, J = 8.0, 1.5 Hz, 1 H).

13C {1H} NMR (100 MHz, CDCl3): δ = 29.7, 34.8, 47.5, 66.8, 116.1, 126.7, 128.2, 128.9, 129.2, 129.7, 130.2, 130.8, 134.9, 135.6, 138.5, 154.2.

HRMS (ES+, Ar): m/z [M + H]+ calcd for C18H18 79Br3ClO: 548.8422; found: 548.8422.


#
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Conflict of Interest

The authors declare no conflict of interest.

Acknowledgment

Dedicated to Prof. Hiriyakkanavar Ila on the occasion of her 80th birthday.

Supporting Information

    Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/a-2353-1722.
  • Supporting Information

Corresponding Author

Irishi N. N. Namboothiri
Department of Chemistry, Indian Institute of Technology Bombay
Mumbai 400 076
India   

Publication History

Received: 21 May 2024

Accepted after revision: 26 June 2024

Accepted Manuscript online:
26 June 2024

Article published online:
25 July 2024

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Figure 1 Organic molecules of biological interest containing a tribromomethyl group
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Scheme 1 Mg-mediated bromoform addition to activated alkenes
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Scheme 2 Scope of p-quinone methides. Reagents and conditions: p-QM 1 (0.2 mmol), Mg (1.6 mmol, 8 equiv), CHBr3 2 (4.4 mmol, 22 equiv), THF (5 mL); isolated yields after silica gel column chromatography. a No characterizable side product, such as 1,8-addition product, was observed in this reaction.
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Scheme 3 Scope of aurone-derived azadienes. Reagents and conditions: azadiene 4 (0.2 mmol), Mg (1.6 mmol, 8 equiv), CHBr3 2 (4.4 mmol, 22 equiv), THF (5 mL); isolated yields after silica gel column chromatography.
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Scheme 4 Proposed anionic mechanism
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Scheme 5 Proposed radical mechanism
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Scheme 6 Control experiments
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Scheme 7 Scale-up and synthetic transformations of tribromomethylated adducts