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Synthesis 2022; 54(09): 2289-2297
DOI: 10.1055/s-0040-1719895
paper

Synthesis of Aryloxiranes and Arylcyclopropanes via Deprotonation of Benzyl Chlorides

Kacper Kisiel
,
Rafał Loska∗
,
Mieczysław Mąkosza∗

This work was supported by the National Science Centre, Poland (Narodowe Centrum Nauki; UMO-2014/15/B/ST5/02180).
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Abstract

Upon the action of strong bases at low temperature, benzyl chloride and its ring-substituted derivatives undergo deprotonation at the benzylic position and the produced carbanions react with aldehydes, ketones and Michael acceptors to form aryl oxiranes and cyclopropanes.


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Key words

epoxides - cyclopropanes - halocarbanions - nucleophilic addition - nucleophilic substitution - Michael acceptors - Darzens reaction

The smallest carbocyclic and heterocyclic rings of cyclopropanes and oxiranes are the key structural elements of a great variety of practically important products, particularly pharmaceuticals, natural products and valuable active intermediates in organic synthesis.[1] [2] Because of that, there is ongoing substantial interest in the synthesis of substituted cyclopropanes and oxiranes. In spite of significant steric strain in these three-membered rings, they are reasonably stable and there is a great variety of synthetic ways to construct them. The two main approaches are cycloaddition of active one-atom agents to double carbon–carbon bonds and 1,3-intramolecular nucleophilic substitution of anions of 1,2-halohydrins and γ-halocarbanions. Thus, one of the main ways to obtain oxiranes is oxidation of alkenes with peroxyacids, dioxiranes and a variety of other oxidation agents that, in fact, proceeds as formal cycloaddition of an electrophilic oxygen atom.[3] The O-anions of halohydrins (readily available via hydroxychlorination of alkenes) generated under basic conditions undergo fast intramolecular substitution to form oxiranes.[4] An alternative way to produce anions of halohydrins, associated with formation of new C–C bonds, is addition of α-chlorocarbanions to carbonyl groups of aldehydes and ketones. Subsequent rapid 1,3-intramolecular substitution in the anionic adducts provides oxiranes in a process known as the Darzens reaction.[5] A similar process takes place in the addition of sulfonium ylides to carbonyl groups followed by 1,3-intramolecular substitution of sulfides to form oxiranes (the Corey–Chaikovsky reaction).[6]

Analogically, cyclopropanes can be synthesized via cycloaddition to alkenes of electron-deficient carbenes generated via α-elimination (e.g., dichlorocarbene or phenylchlorocarbene)[7] or decomposition of aliphatic diazo compounds (e.g., alkyl diazoacetates)[8] or carbenoids (Simmons–Smith reaction).[9] Another important way of synthesizing cyclopropanes is intramolecular 1,3-substitution of γ-halocarbanions, which can be generated via deprotonation of appropriate carbanion precursors such as esters or nitriles of γ-halocarboxylic acids, or γ-haloalkyl sulfones, or alkylation of methylenic carbanions with 1,2-dihaloalkenes[10] and particularly addition of α-halocarbanions to Michael acceptors, often abbreviated as MIRC (Michael Initiated Ring Closure).[11]

A common way of synthesizing aryl substituted oxiranes and cyclopropanes is through reactions of carbonyl compounds and Michael acceptors with ylides generated via deprotonation of benzyldialkyl sulfonium or benzyl trialkylammonium salts.[12]

Halogens exert only moderate carbanion-stabilizing effect, thus α-halocarbanions, as intermediates in the synthesis of oxiranes and cyclopropanes, require the presence of electron-withdrawing, carbanion-stabilizing groups. To this end, α-halocarbanions are usually generated via base-induced deprotonation of precursors such as esters or nitriles of α-halocarboxylic acids, α-haloalkyl sulfones, and α-haloketones. Deprotonation of the α-position in benzyl chlorides has been used in the synthesis of oxiranes and cyclopropanes only with benzyl chlorides containing strongly stabilizing nitro groups in the ortho/para-positions of the aromatic ring or chloromethyl derivatives of strongly electron-poor heterocycles.[13] On the other hand, there are some reports of the synthesis of oxiranes and cyclopropanes via reaction of aldehydes and Michael acceptors with α-chlorobenzylic carbanions generated via electrolytic and chemical reduction of benzylidene dichloride.[14]

Recently, we reported a new general method for the synthesis of diaryl methanes via vicarious nucleophilic substitution of hydrogen (VNS) in nitroarenes by carbanions of benzyl chlorides.[15] VNS is a reaction of α-chlorocarbanions with nitroarenes and other electron-deficient arenes that proceeds via addition of the carbanions to the aromatic rings in positions occupied by hydrogen. Subsequent base-induced β-elimination of hydrogen chloride from the intermediate anionic σH adducts and protonation of the produced nitrobenzylic carbanions gives the substitution products.[16] We found that treatment of BnCl and a variety of ring-substituted benzyl chlorides with a strong base results in deprotonation of the methylenic groups to form α-chlorocarbanions that are sufficiently active and long lived to add to the rings of nitroarenes with the formation of nitrodiarylmethanes.

Electrophilic activities of aldehydes and ketones and also Michael acceptors are, as a rule, higher than electrophilicity of nitroarenes;[17] thus, we expected that carbanions of benzyl chlorides generated in the presence of these electrophilic partners should enter typical reactions of α-chlorocarbanions, namely the Darzens reaction of aldehydes and ketones (Scheme [1]). Herein, we show that even poorly stabilized benzylic carbanions that contain halogen, cyano or just hydrogen substituents in the ring can be captured by electrophiles, overriding such side reactions as α-elimination to carbenes or dimerization and providing an efficient method of synthesis of aryl oxiranes and MIRC-type formation of cyclopropanes.

Zoom Image
Scheme 1 Darzens and Michael-type reactions of carbanions of benzyl chlorides

Carbanions of benzyl chlorides are very unstable entities and their reactions should be carried out at low temperature. Taking into account our experience with VNS reactions of these carbanions, in the preliminary experiments we examined deprotonation of a benzyl chloride derivative (4-cyanobenzyl chloride 1a) at –78 °C with a strong base (KHMDS) in the presence of an electrophile. Already in the first attempt, dropwise addition of a THF solution of 1a (1.2 mmol) and benzaldehyde 2a (1.0 mmol) to a cooled solution of KHMDS (1.3 mmol) provided the expected epoxide 3a in good 85% yield after 15 min (Table [1]). Changing the ratio of substrates 1a/2a to 1:1.2 had negligible effect, whereas decreasing the amount of base led to a significant drop in the yield of 3a.

We then examined the above epoxide synthesis using ring-substituted benzyl chlorides and a variety of carbonyl compounds (Table [1]).

Table 1 Darzens Reaction of Substituted Benzyl Chlorides

Entry

1 (R)

2 (R1, R2)

Product

Yield (%)

trans/cis ratio

1

1a (4-CN)

2a (H, Ph)

3a

85

1:0.45

2

2b (H, 4-ClC6H4)

3b

83

1:0.2

3

2c (H, 4-MeC6H4)

3c

97

1:0.3

4

2d (H, 4-t-BuC6H4)

3d

84

1:0.6

5

2e (-(CH2)5-)

3e

61

6

2f (Ph, Ph)

3f

91

7

2g (CF3, 4-t-BuC6H4)

3g

75

8

1b (2,4-Cl2)

2a

3h

57

1:1

9

1c (3-NO2)

2a

3i

45

1:1.25

Reactions of 1a with aromatic aldehydes gave epoxides 3a–d in good yields, as mixtures of isomers, with the trans-isomer predominating (Table [1], entries 1–4). The yield of oxirane in the reaction with chloride 1b was lower, perhaps due to its lower acidity compared to 1a. Formation of nitrophenyl epoxide 3i was accompanied by decomposition. Importantly, the reaction worked well for ketones, even those containing acidic C–H bonds at the α-position such as cyclohexanone (entry 5).

Similar synthesis of epoxides using unsubstituted benzyl chloride (1d) proved more difficult. Deprotonation of this substrate requires a stronger base, LDA, rather than KHMDS. Unfortunately, even in the presence of LDA the reaction of 1d and aromatic aldehydes gave the expected oxiranes in negligible yields. We suspected that the lack of reaction between the carbanion of 1d and aldehyde could be explained by fast addition of LDA to the carbonyl group, which prevented the aldehyde from reacting with the carbanion. After quenching, such adducts would then dissociate back to aldehyde. Addition of hexamethyl phosphor­amide (HMPA), which is capable of strong solvation of lithium­ cations and accelerating the intramolecular nucleophilic substitution step, did not improve the results. The only outcome of these experiments was self-alkylation of benzyl chloride, leading to 1-chloro-1,2-dichloroethane and trans-stilbene, together with unreacted aldehyde.

Only the use of very bulky base improved the situation: addition of a mixture of 1d and 4-tert-butylbenzaldehyde (2h) to N-lithiated 2,2,6,6-tetramethylpiperidine (LiTMP) and HMPA in THF provided the expected epoxide in moderate yield (21%, 6:1 mixture of trans and cis isomers; Scheme [2a]). Attempts to generate carbanions of 1d in a similar way in advance and their subsequent trapping with aldehyde (added immediately after 1d) resulted only in benzyl chloride self-alkylation. These results are consistent with earlier studies on trimethylsilylation of carbanions of 1d.[18]

On the other hand, 1d reacted efficiently with benzophenone in the presence of LDA and HMPA (Scheme [2b]). Perhaps in this case steric hindrance prevented addition of LDA to the carbonyl group.

Zoom Image
Scheme 2 Reactions of benzyl chloride carbanions with carbonyl compounds

The reaction of unsubstituted benzyl chloride 1d deprotonated with a lithium base (Scheme [2a]) exhibited quite high diastereoselectivity (6:1 dr) in contrast to the reactions performed in the presence of KHMDS (see Table [1]). This difference could be explained by base-induced cis/trans isomerization of 3 under the reaction conditions, but we ruled out this possibility in control experiments in which pure diastereomers of oxiranes 3 were subjected to the standard reaction conditions and underwent no epimerization. Therefore, reactions of some chlorides 1 containing additional stabilizing groups were checked using bulky lithium base LiTMP/HMPA instead of KHMDS with the aim of improving their cis/trans selectivity. Indeed, we found that the preference for trans-isomer formation was much higher with LiTMP, but at the expense of yield: chloride 1a reacted with 2a to give 3a (22%, trans/cis 4.7:1), 1a with 2d gave 3d (13%, trans/cis 5.7:1), and 1b with 2a gave 3h (40%, trans/cis 2.4:1). The difference in the lithium vs. potassium base behavior can perhaps be explained by pre-association of carbanion-bound lithium with the carbonyl oxygen.

Addition of carbanions of benzyl chlorides 1 to α,β-unsaturated carbonyl compounds (Michael acceptors) was expected to give aryl-substituted cyclopropanes. Indeed, deprotonation of 1a or 1b with KHMDS in the presence of acrylates gave cyclopropanecarboxylic esters in good yields, predominantly in trans configuration (Scheme [3]). Aryl vinyl sulfone behaved similarly to provide cyclopropyl sulfone 5h in 74% yield.

Zoom Image
Scheme 3 Synthesis of cyclopropanes from Michael acceptors and carbanions of benzyl chlorides. a Isomers separated by chromatography. Ar = 4-cyanophenyl.

Cylopropanes containing an acidic proton α to an ester or sulfonyl group (5a, 5b, 5h) were formed with high trans selectivity, probably as a result of equilibration under the basic reaction conditions. Exclusive trans relation of the ester and bulky aryl group has also been obtained for the diastereomeric mixture of 5e and 5e′. Generally lower trans selectivity, but still much better than with oxiranes, was obtained for cyclopropanes 5c and 5f that lack acidic protons, but not for 5d, which gave both poor yield and no selectivity.

The reactions of 1 with a strong base and ethyl crotonate, which contains acidic C–H bonds, were more complicated. 4-Cyanobenzyl chloride 1a, which exhibits relatively acidic benzylic protons, underwent deprotonation, nucleophilic addition and cyclization to the expected cyclopropane 5e/5e′ (Scheme [3]). On the other hand, less acidic benzyl chlorides acted instead as alkylating agents for deprotonated crotonate. 3-Trifluoromethylbenzyl chloride 1e gave moderate yield of vinyl derivative 6, which could not be separated from minor amounts of trans-1,2-bis(3-trifluoromethylphenyl)ethene (Scheme [4]).

Zoom Image
Scheme 4 Reaction with a Michael acceptor containing acidic γ-protons

In conclusion, carbanions obtained from benzyl chloride and its ring-substituted derivatives upon the action of strong lithium or potassium bases are long-lived enough to undergo addition to electron-deficient double bonds of aldehydes and Michael acceptors. Subsequent intramolecular substitution of chloride results in the formation of aryl-substituted oxirane and cyclopropane rings, often in good yields and with preference for trans stereochemistry.

Analytical grade solvents were used as received. Hexanes and dichloromethane (DCM) used for extraction and chromatography were distilled before use. Commercially available anhydrous THF, KHMDS, n-BuLi and LDA solutions were used for the oxiranes and cyclopropanes synthesis. All commercially available reagents: benzyl chloride derivatives, carbonyl compounds and Michael acceptors, were used as received. NMR spectra were recorded at 298 K in CDCl3 solutions using a 400 MHz spectrometer. The 1H and 13C NMR chemical shifts are given relative to TMS (δ = 0.0 ppm) and relative to CFCl3 for 19F spectra. Mass spectra and HRMS measurements were obtained with a mass spectrometer equipped with an electrospray ion source and q-TOF type mass analyzer (ES), or a magnetic sector mass spectrometer equipped with an electron impact (EI) ion source and the EBE double focusing geometry mass analyzer. IR spectra were obtained with a FT-IR spectrometer. Melting-point temperatures were measured at a heating rate of 3 °C/min. Column chromatography was performed using silica gel 60 (0.040–0.063 mm). Analytical thin-layer chromatography (TLC) was performed using pre-coated silica gel plates (0.20 mm thickness) and visualized under a UV lamp.


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Synthesis of Oxiranes in the Presence of KHMDS; General Procedure

KHMDS (1 M in THF, 0.65 mL, 0.65 mmol) was placed in a flame-dried Schlenk flask under Ar and cooled to –78 °C. A solution of aldehyde (0.50 mmol) and benzyl chloride (0.60 mmol, 76 mg, 69 μL) in DMF (1 mL) was added dropwise with vigorous magnetic stirring. After 15 min, saturated NH4Claq (2 mL) was added, followed by EtOAc (5 mL) and brine (5 mL). The phases were separated, the organic phase was washed with brine (3 × 10 mL), dried over anhydrous Na2SO4, and evaporated. The products were purified by column chromatography on silica gel using hexanes/EtOAc as eluent.


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trans-2-(4-Cyanophenyl)-3-phenyloxirane (trans-3a)[6c] [d]

Yield: 64 mg (58%); white crystals; mp 65–67 °C (heptane/DCM).

IR (KBr): 3063, 3036, 3009, 2227 (CN), 1962, 1915, 1777, 1659, 1605, 1496, 1459, 1423, 1345, 1280, 1169, 1087, 1026, 878, 827, 760, 696, 614, 553, 496 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.83 (d, 3 J = 1.8 Hz, 1 H, CH–O), 3.92 (d, 3 J = 1.8 Hz, 1 H, CH–O), 7.31–7.43 (m, 5 H, HAr), 7.45 (d, 3 J = 8.3 Hz, 2 H, HAr), 7.66 (d, 3 J = 8.3 Hz, 2 H, HAr).

13C NMR (100 MHz, CDCl3): δ = 61.7, 63.1, 112.0, 118.5, 125.5, 126.1, 128.6, 128.7, 132.3, 136.1, 142.4.

MS (EI+): m/z (%) = 221 (76) [M]+, 203 (18), 192 (89), 165 (19), 115 (24), 90 (100).

HRMS (EI+): m/z [M]+ calcd for C15H11NO: 221.0841; found: 221.0849.


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cis-2-(4-Cyanophenyl)-3-phenyloxirane (cis-3a)[13b] [14a]

Yield: 30 mg (27%); white crystals; mp 95–97 °C (heptane/DCM).

IR (KBr): 3037, 2979, 2225 (CN), 1968, 1928, 1779, 1657, 1606, 1496, 1453, 1415, 1397, 1368, 1293, 1172, 1048, 897, 875, 814, 752, 704, 615, 563, 495 cm–1.

1H NMR (400 MHz, CDCl3): δ = 4.36 (d, 3 J = 4.3 Hz, 1 H, CH–O), 4.43 (d, 3 J = 4.3 Hz, 1 H, CH–O), 7.12–7.21 (m, 5 H, HAr), 7.28 (d, 3 J = 8.5 Hz, 2 H, HAr), 7.45 (d, 3 J = 8.5 Hz, 2 H, HAr).

13C NMR (100 MHz, CDCl3): δ = 58.9, 60.0, 111.4, 118.6, 126.7, 127.5, 127.9, 128.0, 131.6, 133.4, 140.0.

MS (EI+): m/z (%) = 221 (82) [M]+, 203 (24), 192 (93), 165 (27), 115 (31), 90 (100), 77 (26), 63 (35).

HRMS (EI+): m/z [M]+ calcd for C15H11NO: 221.0841; found: 221.0841.


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trans-2-(4-Chlorophenyl)-3-(4-cyanophenyl)oxirane (trans-3b)

Yield: 89 mg (70%); white crystals; mp 98–101 °C (heptane/DCM).

IR (KBr): 3066, 2992, 2224 (CN), 1921, 1605, 1489, 1435, 1406, 1271, 1173, 1085, 1011, 840, 813, 731, 557, 536, 499 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.80 (d, 3 J = 1.7 Hz, 1 H, CH–O), 3.87 (d, 3 J = 1.7 Hz, 1 H, CH–O), 7.27 (d, 3 J = 8.6 Hz, 2 H, HAr), 7.36 (d, 3 J = 8.6 Hz, 2 H, HAr), 7.44 (d, 3 J = 8.2 Hz, 2 H, HAr), 7.67 (d, 3 J = 8.2 Hz, 2 H, HAr).

13C NMR (100 MHz, CDCl3): δ = 61.8, 62.5, 112.2, 118.5, 126.1, 126.9, 128.9, 132.4, 134.6, 134.7, 142.1.

MS (EI+): m/z (%) = 255 (62) [M]+, 237 (13), 226 (68), 220 (65), 190 (35), 124 (52), 89 (100), 63 (35).

HRMS (EI+): m/z [M]+ calcd for C15H10NOCl: 255.0451; found: 255.0455.


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cis-2-(4-Chlorophenyl)-3-(4-cyanophenyl)oxirane (cis-3b)

Yield: 17 mg (13%); white crystals; mp 102–104 °C (heptane/DCM).

IR (KBr): 3094, 2976, 2225 (CN), 1611, 1492, 1420, 1174, 1089, 881, 834, 807, 779, 577, 495 cm–1.

1H NMR (400 MHz, CDCl3): δ = 4.37 (d, 3 J = 4.3 Hz, 1 H, CH–O), 4.38 (d, 3 J = 4.3 Hz, 1 H, CH–O), 7.07 (d, 3 J = 8.4 Hz, 2 H, HAr), 7.17 (d, 3 J = 8.4 Hz, 2 H, HAr), 7.27 (d, 3 J = 8.7 Hz, 2 H, HAr), 7.48 (d, 3 J = 8.7 Hz, 2 H, HAr).

13C NMR (126 MHz, CDCl3): δ = 59.0, 59.3, 111.7, 118.5, 127.4, 128.0, 128.3, 131.8, 131.9, 133.9, 139.5.

MS (EI+): m/z (%) = 255 (74) [M]+, 226 (71), 220 (71), 192 (57), 124 (56), 89 (100), 63 (38).

HRMS (EI+): m/z [M]+ calcd for C15H10NOCl: 255.0451; found: 255.0448.


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2-(4-Cyanophenyl)-3-(4-methylphenyl)oxirane (3c)[6c]

Yield: 85 mg (97%); colorless oil; 1:0.3 trans/cis mixture.

IR (KBr): 3054, 2994, 2925, 2864, 2226 (CN), 1923, 1699, 1606, 1513, 1445, 1276, 1179, 1111, 1016, 885, 815, 734, 575, 548, 527, 501 cm–1.

Major Isomer (trans): 1H NMR (400 MHz, CDCl3): δ = 2.37 (s, 3 H, Me), 3.79 (d, 3 J = 1.7 Hz, 1 H, CH–O), 3.90 (d, 3 J = 1.7 Hz, 1 H, CH–O), 7.20 (d, 3 J = 8.4 Hz, 2 H, HAr), 7.23 (d, 3 J = 8.4 Hz, 2 H, HAr), 7.44 (d, 3 J = 8.3 Hz, 2 H, HAr), 7.66 (d, 3 J = 8.3 Hz, 2 H, HAr).

13C NMR (100 MHz, CDCl3): δ = 21.2, 61.7, 63.3, 112.0, 118.6, 125.5, 126.1, 129.4, 132.4, 133.2, 138.7, 142.6.

Minor Isomer (cis): 1H NMR (400 MHz, CDCl3): δ = 2.24 (s, 3 H, Me), 4.34 (d, 3 J = 4.2 Hz, 1 H, CH–O), 4.39 (d, 3 J = 4.2 Hz, 1 H, CH–O), 6.98 (d, 3 J = 8.3 Hz, 2 H, HAr), 7.02 (d, 3 J = 8.3 Hz, 2 H, HAr), 7.28 (d, 3 J = 8.2 Hz, 2 H, HAr), 7.46 (d, 3 J = 8.2 Hz, 2 H, HAr).

MS (EI+): m/z (%) = 235 (71) [M]+, 220 (69), 206 (100), 192 (53), 130 (36), 104 (77), 91 (41), 78 (60).

HRMS (EI+): m/z [M]+ calcd for C16H13NO: 235.0997; found: 235.0999.


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trans-2-(4-Cyanophenyl)-3-(4-tert-butylphenyl)oxirane (trans-3d)[6c]

Yield: 75 mg (54%); white crystals; mp 109–111 °C (heptane/DCM).

IR (KBr): 3053, 2960, 2869, 2224 (CN), 1928, 1807, 1606, 1506, 1433, 1364, 1268, 1109, 1016, 841, 822, 685, 569 cm–1.

1H NMR (400 MHz, CDCl3): δ = 1.34 (s, 9 H, C(CH3)3), 3.81 (d, 3 J = 1.8 Hz, 1 H, CH–O), 3.93 (d, 3 J = 1.8 Hz, 1 H, CH–O), 7.29 (d, 3 J = 8.4 Hz, 2 H, HAr), 7.44 (d, 3 J = 8.4 Hz, 2 H, HAr), 7.45 (d, 3 J = 8.3 Hz, 2 H, HAr), 7.66 (d, 3 J = 8.3 Hz, 2 H, HAr).

13C NMR (100 MHz, CDCl3): δ = 31.2, 34.6, 61.7, 63.2, 111.9, 118.6, 125.3, 125.6, 126.1, 132.3, 133.2, 142.6, 152.0.

MS (EI+): m/z (%) = 277 (34) [M]+, 262 (40), 248 (65), 220 (100), 193 (30), 131 (75), 115 (51), 91 (52), 57 (66).

HRMS (EI+): m/z [M]+ calcd for C19H19NO: 277.1467; found: 277.1463.


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cis-2-(4-Cyanophenyl)-3-(4-tert-butylphenyl)oxirane (cis-3d)

Yield: 42 mg (30%); white crystals; mp 121–124 °C (heptane/DCM).

IR (KBr): 3073, 2952, 2865, 2228 (CN), 1931, 1812, 1610, 1512, 1463, 1426, 1391, 1361, 1267, 1108, 1046, 1016, 903, 880, 838, 806, 780, 660, 591, 552, 524 cm–1.

1H NMR (400 MHz, CDCl3): δ = 1.23 (s, 9 H, C(CH3)3), 4.34 (d, 3 J = 4.2 Hz, 1 H, CH–O), 4.39 (d, 3 J = 4.2 Hz, 1 H, CH–O), 7.05 (d, 3 J = 8.3 Hz, 2 H, HAr), 7.20 (d, 3 J = 8.3 Hz, 2 H, HAr), 7.29 (d, 3 J = 8.3 Hz, 2 H, HAr), 7.47 (d, 3 J = 8.3 Hz, 2 H, HAr).

13C NMR (100 MHz, CDCl3): δ = 31.2, 34.5, 59.0, 60.0, 111.3, 118.7, 125.0, 126.5, 127.6, 130.2, 131.6, 140.2, 151.0.

MS (EI+): m/z (%) = 277 (29) [M]+, 262 (44), 248 (71), 220 (100), 193 (31), 131 (76), 115 (56), 91 (56), 57 (69).

HRMS (EI+): m/z [M]+ calcd for C19H19NO: 277.1467; found: 277.1473.


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Oxirane (3e)

Yield: 63 mg (61%); pale-yellow oil.

IR (DCM): 3059, 2934, 2856, 2227 (CN), 1931, 1610, 1506, 1447, 1299, 1111, 996, 920, 850, 807, 689, 615, 564 cm–1.

1H NMR (400 MHz, CDCl3): δ = 1.15–1.77 (m, 10 H), 3.86 (s, 1 H, CH–O­), 7.41 (d, 3 J = 8.4 Hz, 2 H, HAr), 7.61 (d, 3 J = 8.4 Hz, 2 H, HAr).

13C NMR (100 MHz, CDCl3): δ = 24.4, 25.2, 25.2, 28.3, 35.3, 63.7, 66.2, 111.1, 118.7, 127.1, 131.7, 141.9.

MS (EI+): m/z (%) = 213 (58) [M]+, 184 (15), 169 (37), 130 (33), 116 (100), 97 (37), 81 (34), 67 (90), 54 (59), 41 (58).

HRMS (EI+): m/z [M]+ calcd for C14H15NO: 213.1154; found: 213.1157.


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3-(4-Cyanophenyl)-2,2-diphenyloxirane (3f)[19]

Yield: 135 mg (91%); white crystals; mp 116–118 °C (heptane/DCM).

IR (KBr): 3059, 2986, 2225 (CN), 1961, 1906, 1823, 1783, 1701, 1606, 1495, 1446, 1416, 1327, 1290, 1254, 1178, 1078, 1027, 915, 853, 825, 762, 696, 635, 588, 552 cm–1.

1H NMR (400 MHz, CDCl3): δ = 4.40 (s, 1 H, CH–O), 7.16–7.25 (m, 7 H, HAr), 7.30–7.45 (7 H, m, HAr).

13C NMR (100 MHz, CDCl3): δ = 66.8, 69.1, 111.3, 118.5, 126.2, 127.2, 127.9, 128.0, 128.1, 128.4, 128.8, 131.4, 134.8, 139.9, 140.8.

MS (EI+): m/z (%) = 297 (34) [M]+, 190 (5), 165 (100), 139 (14), 105 (30), 77 (21).

HRMS (EI+): m/z [M]+ calcd for C21H15NO: 297.1154; found: 297.1146.


#

3-(4-Cyanophenyl)-2-(4-tert-butylphenyl)-2-trifluoromethyloxirane (3g)

Yield: 130 mg (75%); white crystals; mp 115–116 °C (heptane/DCM).

IR (KBr): 3076, 2963, 2871, 2235, 1936, 1821, 1700, 1613, 1513, 1428, 1399, 1343, 1322, 1180, 1111, 957, 938, 894, 852, 827, 744, 698, 624, 546 cm–1.

1H NMR (400 MHz, CDCl3): δ = 1.25 (s, 9 H, C(CH3)3), 4.61 (s, 1 H, CH–O), 7.13 (d, 3 J = 8.4 Hz, 2 H, HAr), 7.16 (d, 3 J = 8.2 Hz, 2 H, HAr), 7.26 (d, 3 J = 8.4 Hz, 2 H, HAr), 7.43 (d, 3 J = 8.2 Hz, 2 H, HAr).

13C NMR (100 MHz, CDCl3): δ = 31.1, 34.7, 59.5 (q, 3 J CF = 2.44 Hz), 64.9 (q, 2 J CF = 36.0 Hz), 112.4, 118.3, 122.8 (q, 1 J CF = 279.8 Hz), 124.1, 125.3, 127.4, 128.7, 131.7, 137.6, 153.0.

19F NMR (376 MHz, CDCl3): δ = –75.03 (s, CF3).

MS (EI+): m/z (%) = 345 (3) [M]+, 330 (27), 289 (63), 276 (7), 248 (38), 199 (30), 130 (25), 115 (39), 57 (100).

HRMS (EI+): m/z [M]+ calcd for C20H18NOF3: 345.1340; found: 345.1341.


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2-(2,4-Dichlorophenyl)-3-phenyloxirane (3h)[20]

Yield: 75 mg (57%); yellow oil; 1:1 trans/cis mixture.

IR (DCM): 3088, 3065, 3033, 2928, 1951, 1905, 1794, 1728, 1701, 1587, 1473, 1381, 1101, 1050, 868, 820, 738, 699, 617, 563, 531 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.74 (d, 3 J = 1.9 Hz, 1 H, CH–O trans), 4.18 (d, 3 J = 1.9 Hz, 1 H, CH–O trans), 4.40 (d, 3 J = 4.3 Hz, 1 H, CH–O cis), 4.46 (d, 3 J = 4.3 Hz, 1 H, CH–O cis), 7.11 (dd, 3 J = 8.3 Hz, 4 J = 2.0 Hz, 1 H, HAr cis), 7.17 (m, 5 H, HAr), 7.18 (d, 4 J = 2.0 Hz, 1 H, HAr cis), 7.27 (m, 1 H, HAr), 7.31 (m, 2 H, HAr), 7.35–7.43 (m, 6 H, HAr).

13C NMR (100 MHz, CDCl3): δ = 58.2, 59.4, 59.4, 62.2, 125.6, 126.4, 126.8, 127.4, 127.7, 127.8, 128.55, 128.56, 128.59, 129.0, 129.6, 131.3, 133.3, 133.6, 133.8, 133.8, 133.9, 134.2, 136.3.

MS (EI+): m/z (%) = 264 (65) [M]+, 246 (13), 235 (87), 229 (50), 201 (60), 194 (57), 173 (64), 165 (83), 123 (94), 105 (60), 90 (100), 77 (62).

HRMS (EI+): m/z [M]+ calcd for C14H10OCl2: 264.0109; found: 264.0104.


#

trans-2-(3-Nitrophenyl)-3-phenyloxirane (trans-3i)[21]

[CAS Reg. No. 69248-58-4]

Yield: 24 mg (20%); yellow oil.

IR (DCM): 3072, 2927, 1731, 1530 (NO2), 1353, 1096, 869, 810, 752, 735, 701, 616 cm–1.

1H NMR (400 MHz, CDCl3): δ = 3.88 (d, 3 J = 1.7 Hz, 1 H, CH–O), 3.98 (d, 3 J = 1.7 Hz, 1 H, CH–O), 7.37 (m, 5 H, Ph), 7.56 (m, 1 H, HAr), 7.68 (d, 3 J = 7.71 Hz, 1 H, HAr), 8.19 (m, 1 H, HAr), 8.22 (m, 1 H, HAr).

MS (EI+): m/z (%) = 241 (39) [M]+, 224 (27), 212 (34), 194 (40), 165 (50), 135 (60), 105 (63), 90 (100), 77 (41), 63 (45).

HRMS (EI+): m/z [M]+ calcd for C14H11NO3: 241.0739; found: 241.0734.


#

cis-2-(3-Nitrophenyl)-3-phenyloxirane (cis-3i)

Yield: 30 mg (25%); orange oil.

IR (DCM): 3066, 2926, 2854, 1529 (NO2), 1350, 1089, 887, 806, 768, 738, 697, 596 cm–1.

1H NMR (400 MHz, CDCl3): δ = 4.42 (d, 3 J = 4.2 Hz, 1 H, CH–O), 4.46 (d, 3 J = 4.2 Hz, 1 H, CH–O), 7.12–7.22 (m, 5 H, Ph), 7.34 (t, 3 J = 7.8 Hz, 1 H, HAr), 7.49 (d, 3 J = 8.1 Hz, 1 H, HAr), 8.00 (m, 1 H, HAr), 8.07 (s, 1 H, HAr).

13C NMR (100 MHz, CDCl3): δ = 58.6, 59.9, 121.9, 122.6, 126.7, 127.9, 128.1, 128.8, 132.7, 133.2, 136.8.

MS (EI+): m/z (%) = 241 (33) [M]+, 224 (23), 212 (34), 194 (34), 165 (56), 135 (65), 105 (69), 90 (100), 77 (39), 63 (51).

HRMS (EI+): m/z [M]+ calcd for C14H11NO3: 241.0739; found: 241.0733.


#

1,1,2-Triphenyloxirane (3j)[13b]

[CAS Reg. No. 4479-98-5]

LDA (2.0 M in THF, 0.30 mL, 0.60 mmol) and anhydrous THF (0.5 mL) were placed in a flame-dried Schlenk flask under Ar and cooled to –78 °C. Then HMPA (1.3 mmol, 0.23 mL) was added and a solution of benzophenone (0.50 mmol, 91 mg) and benzyl chloride (0.60 mmol, 76 mg, 69 μL) in THF (0.5 mL) was added dropwise with vigorous magnetic stirring. After 15 min, saturated NH4Claq (2 mL) was added, followed by EtOAc (5 mL) and brine (5 mL). The work up and purification was performed as described for the procedure with KHMDS to give 1,1,2-triphenyloxirane (3j).

Yield: 126 mg (93%); white crystals; mp 163–164 °C (heptane/CH2Cl2).

IR (DCM): 3060, 3030, 1954, 1688, 1600, 1496, 1448, 1278, 1030, 747, 698, 621, 587 cm–1.

1H NMR (400 MHz, CDCl3): δ = 4.38 (s, 1 H, CH–O), 7.06–7.13 (m, 2 H, HAr), 7.15–7.21 (m, 3 H, HAr), 7.22–7.30 (m, 5 H, HAr), 7.31–7.41 (m, 3 H, HAr), 7.41–7.46 (m, 2 H, HAr).

13C NMR (100 MHz, CDCl3): δ = 68.0, 68.6, 126.3, 126.7, 127.5, 127.6, 127.7, 127.7, 127.8, 128.3, 129.1, 135.4, 135.8, 141.0.

MS (EI+): m/z (%) = 272 (35%) [M]+, 243 (4), 165 (100), 139 (12), 105 (41), 77 (22).

HRMS (EI+): m/z [M]+ calcd for C20H16O: 272.1201; found: 272.1198.


#

1-(4-tert-Butylphenyl)-2-phenyloxirane (3k)[6c] [22]

TMP (1.1 mmol, 155 mg, 186 μL) was dissolved in anhydrous THF (2.0 mL) in a flame-dried Schlenk flask under Ar and cooled to –20 °C. n-BuLi (2.5 M in hexanes, 0.44 mL, 1.1 mmol) was added dropwise and the reaction mixture was stirred for 30 min. The mixture was then cooled to –78 °C and HMPA (2.2 mmol, 394 mg, 383 μL) was added, followed after 2 min by a solution of 4-tert-butylbenzaldehyde (0.60 mmol, 97 mg, 100 μL) and benzyl chloride (0.60 mmol, 76 mg, 69 μL) in anhydrous THF (1.0 mL). The reaction mixture was stirred for 1 h, during which it reached room temperature. Saturated NH4Claq (2 mL) was added, followed by EtOAc (10 mL) and brine (15 mL). The work up and purification was performed as described for the procedure with KHMDS to give 1-(4-tert-butylphenyl)-2-phenyloxirane (3k).

Yield: 32 mg (21%); colorless oil; 6:1 trans/cis mixture.

Major isomer (trans): 1H NMR (600 MHz, CDCl3): δ = 1.36 (s, 9 H), 3.87 (d, 3 J = 1.9 Hz, 1 H, CH–O), 3.91 (d, 3 J = 1.9 Hz, 1 H, CH–O), 7.32 (d, 3 J = 8.2 Hz, 2 H, HAr), 7.36 (m, 3 H, HAr), 7.40 (m, 2 H, HAr), 7.44 (d, 3 J = 8.3 Hz, 2 H, HAr).

13C NMR (100 MHz, CDCl3): δ = 31.3, 34.6, 62.7, 62.8, 125.3, 125.4, 125.5, 128.2, 128.5, 134.1, 137.2, 151.4.

Minor isomer (cis): 1H NMR (400 MHz, CDCl3): δ = 1.24 (s, 9 H), 4.32 (d, 3 J = 4.3 Hz, 1 H, CH–O), 4.34 (d, 3 J = 4.3 Hz, 1 H, CH–O), 7.09 (d, 3 J = 8.2 Hz, 2 H, HAr), 7.19 (m, 7 H, HAr).


#

Synthesis of Cyclopropanes in the Presence of KHMDS

These reactions were performed as described for the preparation of oxiranes with KHMDS (see above), using the appropriate Michael acceptor (0.5 mmol) instead of aldehyde.


#

tert-Butyl trans-2-(4-Cyanophenyl)cyclopropanecarboxylate (trans-5a)[24]

Yield: 100 mg (85%); colorless oil.

1H NMR (400 MHz, CDCl3): δ = 1.23 (ddd, 2 J = 4.7 Hz, 3 J = 8.5, 6.3 Hz, 1 H, CHH), 1.44 (s, 1 H, C(CH3)3), 1.58 (ddd, 2 J = 4.7 Hz, 3 J = 9.2, 5.4 Hz, 1 H, CHH), 1.86–1.86 (ddd, 3 J = 8.5, 5.5, 4.2 Hz, 1 H, CH–CO), 2.44 (ddd, 3 J = 9.2, 6.2, 4.1 Hz, 1 H, CH–Ar), 7.14 (d, 3 J = 8.3 Hz, 2 H, HAr), 7.52 (d, 3 J = 8.3 Hz, 2 H, HAr).

13C NMR (100 MHz, CDCl3): δ = 17.4, 25.3, 25.8, 28.0, 81.0, 109.9, 118.7, 126.7, 132.1, 146.3, 171.5.


#

tert-Butyl cis-2-(4-Cyanophenyl)cyclopropanecarboxylate (cis-5a)[24]

Yield: 14 mg (12%); colorless oil.

1H NMR (400 MHz, CDCl3): δ = 1.16 (s, 9 H, C(CH3)3), 1.33 (m, 1 H, CHH), 1.65 (m, 1 H, CHH), 2.07 (m, 1 H, CH–CO), 2.52 (m, 1 H, CH–Ar), 7.37 (d, 3 J = 8.2 Hz, 2 H, HAr), 7.55 (d, 3 J = 8.2 Hz, 1 H, HAr).

13C NMR (100 MHz, CDCl3): δ = 10.9, 23.3, 24.9, 27.8, 80.7, 110.3, 130.2, 131.6, 169.6 (other quaternary signals not observed).


#

tert-Butyl 2-(3-Trifluoromethylphenyl)cyclopropanecarboxylate (5b)[24]

Yield: 119 mg (83%); colorless oil; 5:1 trans/cis mixture.

IR (DCM): 2980, 2933, 1721 (C=O), 1330, 1161, 1128, 799, 700 cm–1.

Major isomer (trans): 1H NMR (500 MHz, CDCl3): δ = 1.26 (m, 1 H, CHH), 1.48 (s, 9 H, C(CH3)3), 1.59 (m, 1 H, CHH), 1.87 (m, 1 H, CH–CO), 2.50 (m, 1 H, CH–Ar), 7.33 (d, 3 J = 8.0 Hz, 1 H, HAr), 7.39 (s, 1 H, HAr), 7.44 (t, 3 J = 7.7 Hz, 1 H, HAr), 7.51 (d, 3 J = 7.4 Hz, 1 H, HAr).

13C NMR (125 MHz, CDCl3): δ = 17.0, 25.2, 25.3, 28.1, 80.9, 122.9 (q, 3 J CF = 3.8 Hz), 123.1 (q, 3 J CF = 3.8 Hz), 124.1 (q, 1 J CF = 272.5 Hz), 128.8, 129.5 (q, 4 J CF = 1.1 Hz), 130.8 (q, 2 J CF = 32.2 Hz), 141.6, 172.0.

Minor isomer (cis): 1.20 (s, 9 H, C(CH3)3), 1.29 (m, 1 H, CHH), 1.67 (m, 1 H, CHH), 2.10 (m, 1 H, CH–CO), 2.60 (m, 1 H, CH–Ar), 7.56 (m, 1 H, HAr), 7.60 (m, 1 H, HAr), 7.75 (d, 3 J = 7.7 Hz, 1 H, HAr), 7.83 (s, 1 H, HAr).

Anal. Calcd for C15H17F3O2: C, 62.93; H, 5.99; F, 19.91. Found: C, 62.70; H, 5.74; F, 19.85.


#

Methyl 2-(4-Cyanophenyl)-1-methylcyclopropanecarboxylate (5c)[23]

Yield: 79 mg (73%); yellow oil; 3.4:1 trans/cis mixture.

IR (DCM): 2952, 2227 (CN), 1928, 1722 (C=O), 1608, 1439, 1307, 1275, 1195, 1160, 849, 556 cm–1.

Major isomer (trans): 1H NMR (400 MHz, CDCl3): δ = 0.95 (s, 3 H, CH3), 1.17 (dd, 2 J = 4.8 Hz, 3 J = 7.1 Hz, 1 H, CHH), 1.72 (dd, 2 J = 4.8 Hz, 3 J = 9.0 Hz, 1 H, CHH), 2.80 (dd, 3 J = 9.0, 7.1 Hz, 1 H, CH–Ar), 3.70 (s, 3 H, OMe), 7.27 (d, 3 J = 8.1 Hz, 2 H, HAr), 7.56 (d, 3 J = 8.1 Hz, 2 H, HAr).

13C NMR (100 MHz, CDCl3): δ = 14.3, 20.0, 25.6, 31.2, 52.1, 110.5, 118.6, 129.9, 131.9, 142.6, 175.1.

Minor isomer (cis): 1H NMR (400 MHz, CDCl3): δ = 1.21 (m, 1 H, CHH), 1.48 (s, 3 H, CH3), 1.93 (dd, 2 J = 5.2 Hz, 3 J = 7.3 Hz, 1 H, CHH), 2.31 (m, 1 H, CH–Ar), 3.32 (s, 3 H, OMe), 7.28 (m, 2 H, HAr), 7.50 (d, 3 J = 8.3 Hz, 2 H, HAr).

13C NMR (100 MHz, CDCl3): δ = 19.3, 21.0, 28.6, 33.5, 51.5, 110.1, 118.8, 129.7, 131.5, 142.9, 172.1.

MS (EI+): m/z (%) = 215 (56) [M]+, 183 (37), 156 (100), 146 (38), 116 (48).

HRMS (EI+): m/z [M]+ calcd for C13H13NO2: 215.0946; found: 215.0951.


#

Methyl 2-(2,4-Dichlorophenyl)-1-methylcyclopropanecarboxylate (5d)

Yield: 47 mg (38%); yellow oil; 1:1 trans/cis mixture.

trans-5d: 1H NMR (400 MHz, CDCl3): δ = 0.93 (s, 3 H, CH3), 1.12 (dd, 2 J = 4.7 Hz, 3 J = 7.2 Hz, 1 H, CHH), 1.74 (dd, 2 J = 4.7 Hz, 3 J = 9.0 Hz, 1 H, CHH), 2.74 (dd, 3 J = 9.0, 7.2 Hz, 1 H, CH–Ar), 3.73 (s, 3 H, OMe), 7.04 (d, 3 J = 8.3 Hz, 1 H, HAr), 7.18 (dd, 3 J = 8.3 Hz, 4 J = 2.1 Hz, 1 H, HAr), 7.39 (d, 4 J = 2.1 Hz, 1 H, HAr).

13C NMR (100 MHz, CDCl3): δ = 14.1, 20.1, 25.0, 30.1, 52.2, 126.8, 129.1, 130.6, 132.8, 134.2, 137.3, 175.4.

cis-5d: 1H NMR (400 MHz, CDCl3): δ = 1.21 (dd, 2 J = 4.9 Hz, 3 J = 8.6 Hz, 1 H, CHH), 1.53 (s, 3 H, CH3), 1.86 (dd, 2 J = 4.9 Hz, 3 J = 7.5 Hz, 1 H, CHH), 2.24 (dd, 3 J = 8.5, 7.5 Hz, 1 H, CH–Ar), 3.40 (s, 3 H, OMe), 7.15 (m, 2 H, HAr), 7.31 (m, 1 H, HAr).

13C NMR (100 MHz, CDCl3): δ = 20.0, 20.5, 27.3, 32.4, 51.6, 126.5, 128.5, 131.4, 133.3, 134.4, 136.5, 172.7.

MS (EI+): m/z (%) = 258 (64) [M]+, 226 (46), 199 (100), 189 (46), 164 (62), 159 (48), 127 (58), 129 (41).

HRMS (EI+): m/z [M]+ calcd for C12H12Cl2O2: 258.0214; found: 258.0216.


#

Methyl trans-2-(4-Cyanophenyl)-trans-3-methyl-(R)-1-cyclopropanecarboxylate (5e)

Yield: 73 mg (68%); yellow oil.

IR (DCM): 2955, 2227 (CN), 1728 (C=O), 1609, 1443, 1319, 1198, 1175, 1066, 832, 569 cm–1.

1H NMR (400 MHz, CDCl3): δ = 0.90 (d, 3 J = 5.7 Hz, 3 H, CHCH3 ), 1.81–1.94 (m, CHCH3, 2 H, CH–CO2Me), 2.77 (dd, 3 J = 9.5, 5.7 Hz, 1 H, CH–Ar), 3.72 (s, 3 H, OMe), 7.28 (d, 3 J = 8.3 Hz, 2 H, HAr), 7.58 (d, 3 J = 8.3 Hz, 2 H, HAr).

13C NMR (100 MHz, CDCl3): δ = 12.4, 23.6, 26.7, 31.4, 52.0, 110.5, 118.7, 129.7, 132.0, 142.2, 173.5.

MS (EI+): m/z (%) = 215 (41) [M]+, 184 (28), 156 (100), 140 (31), 116 (49).

HRMS (EI+): m/z [M]+ calcd for C13H13NO2: 215.0946; found: 215.0950.


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Methyl trans-2-(4-Cyanophenyl)-cis-3-methyl-(R)-1-cyclopropanecarboxylate (5e′)

Yield: 23 mg (21%); yellow oil.

1H NMR (400 MHz, CDCl3): δ = 1.36 (d, 3 J = 6.2 Hz, 3 H, CHCH3 ), 1.65–1.75 (dm, 3 J = 9.3, 6.2 Hz, 1 H, CHCH3), 2.08 (dd, 3 J = 9.3, 5.0 Hz, 1 H, CH–CO2Me), 2.44 (dd, 3 J = 6.2, 5.0 Hz, 1 H, CH–Ar), 3.72 (s, 3 H, OMe), 7.15 (d, 3 J = 8.3 Hz, 1 H, HAr), 7.55 (d, 3 J = 8.3 Hz, 1 H, HAr).


#

1-Cyano-3-(4-Cyanophenyl)-1-phenyl-2-isopropylcyclopropane (5f)

Yield: 87 mg (61%); yellow oil; 5:1 trans/cis mixture.

IR (DCM): 3062, 3033, 2962, 2871, 2229 (CN), 1927, 1808, 1653, 1605, 1498, 1452, 1389, 1269, 846, 742, 700, 553 cm–1.

Major isomer (trans): 1H NMR (400 MHz, CDCl3): δ = 1.22 (d, 3 J = 6.7 Hz, 3 H, CH(CH 3)2), 1.36 (d, 3 J = 6.6 Hz, 3 H, CH(CH 3)2), 1.81 (m, 1 H, CH(CH3)2), 2.01 (dd, 3 J = 10.1, 7.3 Hz, 1 H, CH–iPr), 2.83 (d, 3 J = 7.3 Hz, 1 H, CH–Ar), 6.92 (d, 3 J = 8.4 Hz, 2 H, HAr), 7.05 (m, 2 H, HAr), 7.19 (m, 3 H, HAr), 7.38 (d, 3 J = 8.4 Hz, 2 H, HAr).

13C NMR (100 MHz, CDCl3): δ = 21.59, 21.61, 28.5, 31.4, 38.3, 39.1, 111.0, 118.4, 120.8, 128.5, 128.8, 129.0, 129.5, 131.5, 131.8, 140.0.

Minor isomer (cis): 1H NMR (400 MHz, CDCl3): δ = 0.94 (d, 3 J = 5.5 Hz, 3 H, CH(CH 3)2), 1.05 (d, 3 J = 5.0 Hz, 3 H, CH(CH 3)2), 1.81 (m, 1 H, CH(CH3)2), 1.98 (m, 1 H, CH–iPr), 2.95 (d, 3 J = 7.5 Hz, 1 H, CH–Ar), 7.37–7.45 (m, 3 H, HAr), 7.49 (m, 4 H, HAr), 7.69 (d, 3 J = 8.4 Hz, 2 H, HAr).

13C NMR (100 MHz, CDCl3): δ = 22.0, 22.0, 27.7, 29.3, 33.2, 42.7, 128.6, 128.9, 129.2, 131.5, 132.5, 138.7 (other quaternary signals not observed).

MS (EI+): m/z (%) = 286 (29) [M]+, 259 (28), 244 (88), 230 (32), 216 (26), 179 (100), 142 (41), 119 (56), 105 (55), 77 (38).

HRMS (EI+): m/z [M]+ calcd for C20H18N2: 286.1470; found: 286.1473.


#

3-(4-Cyanophenyl)-1,1-bis(ethoxycarbonyl)-2,2-dimethylcyclopropane (5g).

Yield: 118 mg (94%); pale-yellow oil.

IR (DCM): 2982, 2228 (CN), 1729 (C=O), 1608, 1464, 1369, 1309, 1245, 1195, 1106, 1023, 860, 561 cm–1.

1H NMR (400 MHz, CDCl3): δ = 1.17 (t, 3 J = 7.1 Hz, 3 H, CH2CH3 ), 1.29 (t, 3 J = 7.1 Hz, 3 H, CH2CH 3), 1.33 (s, 3 H, CH3), 1.36 (s, 3 H, CH3), 2.99 (s, 1 H, CH), 4.00–4.12 (m, 2 H, CH 2CH3), 4.16–4.32 (m, 2 H, CH 2CH3), 7.31 (d, 3 J = 8.2 Hz, 2 H, HAr), 7.54 (d, 3 J = 8.2 Hz, 2 H, HAr).

13C NMR (100 MHz, CDCl3): δ = 13.9, 14.1, 18.6, 23.8, 31.2, 39.3, 43.8, 61.1, 61.7, 110.7, 118.7, 130.6, 131.7, 140.5, 166.8, 168.6.

HRMS (ESI): m/z [M + Na]+ calcd for C18H21NO4Na: 338.1368; found: 338.1354.


#

trans-2-(4-Cyanophenyl)-1-(4-chlorophenylsulfonyl)cyclopropane (5h)

Yield: 118 mg (74%); pale-yellow oil.

IR (DCM): 2559, 2230 (CN), 1919, 1609, 1583, 1509, 1476, 1394, 1323, 1151, 1090, 1014, 831 cm–1.

1H NMR (500 MHz, CDCl3): δ = 1.51 (m, 1 H), 1.92 (m, 1 H), 2.71 (m, 1 H), 2.92 (m, 1 H), 7.13 (d, 3 J = 8.2 Hz, 2 H, HAr), 7.54 (m, 4 H, HAr), 7.85 (d, 3 J = 8.6 Hz, 2 H, HAr).

13C NMR (125 MHz, CDCl3): δ = 14.6, 23.5, 42.2, 111.2, 118.3, 127.3, 129.1, 129.8, 132.5, 138.5, 140.6, 142.8.

Anal. Calcd for C16H12ClNO2S: C, 60.47; H, 3.81; Cl, 11.16; N, 4.41; S, 10.09. Found: C, 60.24; H, 3.75; Cl, 11.26; N, 4.46; S, 9.85.


#

Ethyl 2-Methyl-2-(3-trifluoromethylbenzyl)but-3-enoate (6)

Yield: 99 mg (35%); inseparable mixture with trans-1,2-bis(3-trifluoromethylphenyl)ethene (18 mg, 10%); colorless oil.

1H NMR (500 MHz, CDCl3): δ = 1.23 (t, 3 J = 7.0 Hz, 3 H, OCH2 CH3 ), 1.25 (s, 3 H, CH3), 2.92 (d, 2 J = 13.3 Hz, 1 H, CHHAr), 3.14 (d, 2 J = 13.3 Hz, 1 H, CHHAr), 4.14 (q, 3 J = 7.1 Hz, 2 H, OCH 2CH3), 5.09 (d, 3 J = 17.5 Hz, 1 H, =CHHtrans ), 5.16 (d, 3 J = 10.7 Hz, 1 H, =CHHcis ), 6.08 (dd, 3 J = 17.5, 10.8 Hz, 1 H, CH=CH2), 7.32 (d, 3 J = 7.7 Hz, 1 H, HAr), 7.37 (t, 3 J = 7.6 Hz, 1 H, HAr), 7.40 (s, 1 H, HAr), 7.48 (m, 1 H, HAr).

13C NMR (125 MHz, CDCl3): δ = 14.0, 20.1, 45.0, 49.7, 114.4, 61.0, 123.4 (q, 3 J CF = 3.9 Hz), 124.1 (q, 1 J CF = 272.4 Hz), 127.0 (q, 3 J CF = 3.8 Hz), 128.3, 130.3 (q, 2 J CF = 32.1 Hz), 133.7, 138.2, 141.0, 174.8.


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Conflict of Interest

The authors declare no conflict of interest.

Supporting Information

    Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/s-0040-1719895.
  • Supporting Information

Corresponding Authors

Rafał Loska
Kasprzaka 44/52, 01-224 Warsaw
Poland   

Mieczysław Mąkosza
Kasprzaka 44/52, 01-224 Warsaw
Poland   

Publication History

Received: 10 December 2021

Accepted after revision: 21 December 2021

Article published online:
21 February 2022

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Zoom Image
Scheme 1 Darzens and Michael-type reactions of carbanions of benzyl chlorides
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Scheme 2 Reactions of benzyl chloride carbanions with carbonyl compounds
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Scheme 3 Synthesis of cyclopropanes from Michael acceptors and carbanions of benzyl chlorides. a Isomers separated by chromatography. Ar = 4-cyanophenyl.
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Scheme 4 Reaction with a Michael acceptor containing acidic γ-protons