CsF-Promoted Iodocyclization of Allenylphosphonates: A Convenient Approach to Highly Functionalized Oxaphospholenes

Abstract

A convenient CsF-promoted iodocyclization reaction of trisubstituted allenylphosphonates with iodine to construct highly functionalized oxaphospholene derivatives has been developed. A series of readily available starting materials including ferrocenylallenes, aromatic and alkyl substituted allenes can undergo the process successfully.

Phosphorus-containing heterocycle compounds have been recognized as valuable organic molecules, and they are used widely in pharmaceutical and agricultural chemistry as insecticides, bactericides, and antibiotic reagents.[1] Among them, oxaphospholenes display superior bioactivities and are constantly used as precursors for furanose carbohydrate mimics.[2] For example, 1,2-oxaphosphol-3-ene 2-oxide compounds I and II have fungistatic activities, and III and IV were reported to have herbicidal activities (Figure [1]).[3] Therefore, efficient and practical strategies for the construction of highly functionalized oxaphospholenes are essential and have been broadly studied.[4] Among these approaches, the electrophile-induced cyclization reaction of the allenylphosphonates in an intramolecular manner has been shown to be an efficient and straightforward method for the synthesis of oxaphospholenes.[5]

Table 1 Optimization of Reaction Conditions^a

Entry	Solvent	Additive	Temp. (°C)	Yield (%)b
1	CH3CN	–	80	46
2	DMF	–	80	45
3	toluene	–	80	34
4	CH3CN	CsF	80	58
5	toluene	CsF	80	64
6	toluene	KF	80	54
7	toluene	NH4F	80	52
8	toluene	AgF	80	trace
9	toluene	TBAF	80	0
10	toluene	KCl	80	48
11	toluene	KBr	80	42
12	toluene	KI	80	37
13c	toluene	CsF	80	68
14	toluene	CsF	90	51
15	toluene	CsF	70	62

^a Reaction conditions: 1a (0.20 mmol), I₂ (0.20 mmol), additive (0.30 mmol), solvent (2.0 mL) for 3 h.

^b Yield of the isolated product.

^c The ratio of 1a/CsF/iodine was 1.0:2.0:1.0.

On the other hand, since its discovery in 1951 by Kealy and Pausonl,[6] ferrocene has remained an important molecule of continuing interest in organometallic chemistry for 70 years. Ferrocene derivatives have been studied widely in the area of asymmetric catalysis, functional molecules, material science, and bioorganometallic chemistry because of their unique physical and chemical properties.[7] Furthermore, some specially designed ferrocene compounds are confirmed as valuable candidates for antimalarial and anticancer therapies in the medicinal field.[8] Consequently, the integration of a ferrocenyl moiety into oxaphospholene skeletons may increase their biological activities or produce new medicinal properties. However, despite this importance, to our knowledge, there is no report describing the synthesis of such ferrocene-containing oxaphospholenes. As a continuation of our interest in the preparation and transformation of ferrocenylallenes,[9] herein we report a convenient approach for the synthesis of new derivatives of ferrocene-containing oxaphospholenes from ferrocenylallenylphosphonates in the presence of iodine, promoted by CsF. In addition, this method has been extended to the synthesis of more general phenyl and alkyl substituted oxaphospholene derivatives.

We started our studies by selecting ferrocene-containing 1,2-allenylphosphonate 1a and iodine as model substrates (Table [1]). First, several solvents such as CH₃CN, DMF, and toluene were tested; it was found that the corresponding 1,2-oxaphosphole 2-oxide 2a was formed in 34–46% yield (entries 1–3). Gratifyingly, when CsF was included as an additive in the reaction, the isolated yield was improved significantly (entries 4 and 5). Subsequently, the effect of additives was investigated in detail. It was found that no better results were obtained when other halide additives were used in place of CsF (entries 6–12). Furthermore, when the ratio of substrates was examined, it was found that a 1a/CsF/I₂ ratio of 1:2:1 led to the highest yield of product 2a (entry 13). Finally, when increasing or reducing the reaction temperature to 90 and 70 °C, respectively, the yield of the product was decreased slightly (entries 14 and 15). The exact structure of 2a was unambiguously confirmed by X-ray crystallographic analysis (Figure [2]).[10]

To define the versatility of this transformation, we next investigated the substrate scope carefully by using various ferrocenylallenylphosphonates 1 with iodine (Scheme [1]). The CsF-promoted iodocyclization reaction proceeded smoothly over a broad range of allene substrates to deliver the corresponding ferrocene-containing oxaphospholenes 2a–j in 23–74% yields. Generally, fluoro, chloro and bromo substituents on the para-position of the phenyl ring were all tolerated, affording the corresponding products 2b–d in moderate to good yields. The substrates with a phenyl ring bearing an electron-donating group (-OCH₃) and an electronic neutral group (-C₆H₅) generally gave slightly higher yields of the products (2e–f). However, sterically hindered allenylphosphonates, bearing 4-tert-butyl and 3,5-dimethyl substituents on the phenyl ring, only provided the oxaphospholenes 2g,h in 30 and 23% yield, respectively. It should be noted that the slightly higher diastereoselectivity of 2g may be caused by the stereoscopic effect of the tert butyl group. Moreover, instead of an aromatic ring group, the corresponding product 2i was obtained in moderate yield when an alkyl substituent was introduced. In addition, to our delight, the 1′-arylmethyl substituted ferrocene-containing allenylphosphonate underwent the iodocyclization reaction smoothly to afford 2j in 68% yield as a single diastereomer. Furthermore, when an ethyl ester of allenyl phosphonic acid was employed as the substrate in this transformation, only a complex mixture was obtained.

Subsequently, to further highlight the full capability of this method, we also investigated the reactivity of other allenylphosphonate substrates by exchanging ferrocene with more general phenyl and alkyl substituents (Scheme [2]). Gratifyingly, under the same reaction conditions, the expected oxaphospholene product 4a was obtained in 76% yield with 1:1 diastereomers when allenyl phosphonate 3a was employed as the substrate. The results indicate that different substituents on the benzene ring of R¹, such as methyl, methoxy, bromo, and dimethylamino, were all suitable, and the corresponding products 4b–e were afforded in 57–80% yield. It should be noted that a free hydroxyl group on the benzene ring was confirmed to be applicable, albeit with a slightly lower yield of product 4f. However, substrate with an ortho-substituted phenyl ring only furnished the product 4g in 17% yield, probably due to steric hindrance. Moreover, oxaphospholene 4h, bearing a heteroaromatic functionality, was also readily synthesized in moderate yield. Notably, when a cyclohexene or an alkyl substituted allenylphosphonate was used as the substrate, the desired products 4i and 4j were formed in 67 and 63% yields, respectively. In addition, with regard to the R² group of the allenylphosphonates, various substituents on the phenyl ring were all well-tolerated for this reaction, affording the functionalized oxaphospholene products 4k–p with good yields. Furthermore, except for aromatic ring groups of R², the alkyl substituent could also be installed to the oxaphospholene with a moderate yield as a single diastereomer (4q).

It should be mentioned that the cyclization reaction was also successfully extended to selenium electrophilic reagents, providing a novel oxaphospholene compound 5 containing both ferrocene and selenium (Scheme [3]). Therefore, treatment of ferrocenyl substituted allenylphosphonate 1a with 1.2 equiv of PhSeX (Cl, Br) in CH₃CN/H₂O = 20:1 at 0 °C for 5 hours led to the desired product 5 in 66 and 48% yields, respectively. The molecular structure of 5 was unambiguously confirmed by X-ray diffraction analysis (Figure [3]).[11]

Finally, a plausible mechanism was proposed for the formation of oxaphospholene products as shown in Scheme [4]. First, electrophilic addition of I₂ to the relatively electron-rich C=C bond of allenic phosphonate 1a affords iodonium intermediate A. Subsequently, a five-membered ring intermediate B is formed through intramolecular nucleophilic attack of the oxygen atom of the phosphate group. Finally, the oxaphospholene product 2a is generated assisted by CsF, which is accompanied by the elimination of MeF.

In summary, we have established a convenient and efficient method to construct highly functionalized oxaphospholene derivatives through CsF-promoted iodocyclization reaction of allenic phosphonates with iodine. A series of readily available starting materials including ferrocenylallenes, aromatic and alkyl substituted allenes can undergo the process successfully with moderate to good yields of the oxaphospholene products. Additionally, this method is applicable to seleniumcyclization reaction using PhSeX (Cl, Br) as the electrophilic reagent to afford phenylselenide-substituted oxaphospholene.

All commercially available reagents were used directly without purification unless otherwise stated. All solvents were purified by following standard procedures. For chromatography, 200–300 mesh silica gel (Qingdao, China) was employed. ¹H, ³¹P and ¹³C NMR spectra were recorded at 500, 202 and 125 MHz, respectively. Chemical shifts are reported in ppm using tetramethylsilane as internal standard when CDCl₃ and DMSO were used as solvent. IR spectra were recorded with a FT-IR instrument. HRMS analysis was obtained with a QTOF mass spectrometer. Melting points were determined with a melting point apparatus and are uncorrected. Allenylphosphonates 1 were prepared according to our previously described procedures.[9a]

Electrophilic Cyclization of Allenylphosphonates with Iodine; General Procedure

To a solution of allenylphosphonate (0.20 mmol) and iodine (0.20 mmol) in toluene (2.0 mL) was added CsF (0.40 mmol) under an air atmosphere. The resulting mixture was stirred at 80 °C for 3 hours. After completion of the reaction, the mixture was cooled to room temperature. The solvent was removed in vacuum, and the resulting residue was purified on a silica gel column (petroleum ether/EtOAc = 5:1) to afford the yellow and white solid products 2 and 4 (see the Supporting Information).

4-Iodo-2-methoxy-3-phenyl-5-ferrocenyl-5H-1,2-oxaphosphole 2-Oxide (2a)

Yield: 88 mg (68%); yellow solid; dr = 1:1; R_f = 0.52 (petroleum ether/EtOAc = 5:1); mp 168–169 °C.

IR (neat): 3094, 2951, 2920, 2849, 1590, 1490, 1444, 1253, 1106, 1038, 992, 961, 917, 867, 806, 778, 697, 605, 544 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.63 (dd, J = 7.8, 1.4 Hz, 4 H), 7.43 (d, J = 6.7 Hz, 4 H), 5.61 (d, J = 7.9 Hz, 1 H), 5.56 (d, J = 6.8 Hz, 1 H), 4.53–4.49 (m, 2 H), 4.44–4.41 (m, 1 H), 4.32 (s, 5 H), 4.31 (d, J = 4.0 Hz, 5 H), 4.29–4.26 (m, 3 H), 4.25 (dd, J = 3.8, 2.2 Hz, 1 H), 4.23 (dd, J = 3.6, 2.3 Hz, 1 H), 3.87 (d, J = 11.6 Hz, 3 H), 3.81 (d, J = 11.9 Hz, 3 H).

³¹P NMR (202 MHz, CDCl₃): δ = 30.1, 29.5.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 133.9, 133.7, 132.7, 132.6, 131.6 (d, J _pc = 7.5 Hz), 131.5 (d, J _pc = 7.5 Hz), 129.4, 129.3, 128.8 (d, J _pc = 1.9 Hz), 128.0 (dd, J _pc = 11.8, 5.7 Hz), 118.2 (d, J _pc = 37.5 Hz), 117.6 (d, J _pc = 38.8 Hz), 84.9 (d, J = 7.6 Hz), 84.7 (t, J = 2.5 Hz), 69.3 (d, J _pc = 1.3 Hz), 69.1 (d, J _pc = 13.2 Hz), 68.0 (d, J _pc = 8.4 Hz), 65.0, 64.6, 54.5 (d, J _pc = 6.7 Hz), 54.3 (d, J _pc = 6.6 Hz).

HRMS (ESI): m/z [M + K]⁺ calcd for C₂₀H₁₈FeIO₃PK: 558.9019; found: 558.9025.

3-(4-Fluorophenyl)-4-iodo-2-methoxy-5-ferrocenyl-5H-1,2-oxaphosphole 2-Oxide (2b)

Yield: 97 mg (68%); yellow solid; dr = 2:1; R_f = 0.45 (petroleum ether/EtOAc = 5:1); mp 128–129 °C.

IR (neat): 2922, 2851, 1720, 1603, 1506, 1412, 1233, 1161, 1106, 1039, 992, 917, 820, 772, 540 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 8.15 (dd, J = 7.8, 5.7 Hz, 1 H), 7.70–7.59 (m, 2 H), 7.19–7.11 (m, 4 H), 5.62 (d, J = 8.1 Hz, 0.5 H), 5.56 (d, J = 6.6 Hz, 1 H), 4.53–4.49 (m, 1 H), 4.42 (s, 1 H), 4.33 (s, 5 H), 4.31 (s, 2 H), 4.29 (s, 2 H), 4.27–4.23 (m, 2 H), 3.90 (d, J = 11.6 Hz, 1.4 H), 3.83 (d, J = 11.9 Hz, 3 H).

³¹P NMR (202 MHz, CDCl₃): δ = 29.9, 29.3.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 163.2 (d, J _Fc = 252.5 Hz), 132.8, 130.2, 130.1 (d, J _pc = 11.3 Hz), 130.0 (d, J _pc = 5.0 Hz), 115.9 (d, J _pc = 21.9 Hz), 115.7 (d, J _pc = 22.5 Hz), 85.0 (d, J _pc = 7.5 Hz), 84.6 (d, J _pc = 2.5 Hz), 70.6 (d, J _pc = 7.1 Hz), 69.3, 69.2 (d, J _pc = 17.5 Hz), 68.0 (d, J _pc = 9.2 Hz), 64.7 (d, J _pc = 53.8 Hz), 54.6 (d, J _pc = 8.8 Hz), 54.3 (d, J _pc = 6.3 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₀H₁₇FFeIO₃PNa: 560.9185; found: 560.9156.

3-(4-Chlorophenyl)-4-iodo-2-methoxy-5-ferrocenyl-5H-1,2-oxaphosphole 2-Oxide (2c)

Yield: 64 mg (42%); yellow solid; >99:1 dr; R_f = 0.48 (petroleum ether/EtOAc = 5:1); mp 156–157 °C.

IR (neat): 2924, 2853, 1718, 1587, 1488, 1250, 1091, 1039, 991, 963, 917, 873, 777, 736, 542 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.60 (d, J = 7.5 Hz, 2 H), 7.43 (d, J = 8.4 Hz, 2 H), 5.56 (d, J = 6.7 Hz, 1 H), 4.50 (s, 1 H), 4.41 (s, 1 H), 4.32 (d, J = 7.5 Hz, 5 H), 4.29 (s, 1 H), 4.25 (s, 1 H), 3.83 (d, J = 11.9 Hz, 3 H).

³¹P NMR (202 MHz, CDCl₃): δ = 29.2.

¹³C NMR (125 MHz, CDCl₃): δ = 135.5, 132.8, 131.6, 129.9 (d, J = 11.4 Hz), 129.4 (d, J = 5.7 Hz), 129.1, 118.9 (d, J = 37.5 Hz), 85.1 (d, J = 7.5 Hz), 84.5, 70.6, 69.3, 69.1 (d, J = 15.0 Hz), 68.1 (d, J = 10.0 Hz), 64.7 (d, J = 52.5 Hz), 54.4 (d, J = 6.7 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₀H₁₇ClFeIO₃PNa: 576.8890; found: 576.8865.

3-(4-Bromophenyl)-4-iodo-2-methoxy-5-ferrocenyl-5H-1,2-oxaphosphole 2-Oxide (2d)

Yield: 83 mg (60%); yellow solid; >99:1 dr; R_f = 0.52 (petroleum ether/EtOAc = 5:1); mp 151–152 °C.

IR (neat): 2923, 2852, 1718, 1582, 1484, 1264, 1105, 1039, 992, 962, 917, 871, 803, 777, 739, 540 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.59 (d, J = 8.4 Hz, 2 H), 7.53 (d, J = 7.7 Hz, 2 H), 5.55 (d, J = 6.7 Hz, 1 H), 4.50 (s, 1 H), 4.41 (s, 1 H), 4.33 (s, 5 H), 4.29 (s, 1 H), 4.25 (s, 1 H), 3.83 (d, J = 11.9 Hz, 3 H).

³¹P NMR (202 MHz, CDCl₃): δ = 29.0.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 132.1, 130.4 (d, J _pc = 11.2 Hz), 129.6 (d, J _pc = 5.7 Hz), 123.8, 100.0, 85.1 (d, J _pc = 7.5 Hz), 84.4, 70.6, 69.3, 69.2, 69.1, 68.0, 64.9, 64.4, 54.4 (d, J _pc = 6.6 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₀H₁₇BrFeIO₃PNa: 620.8386; found: 620.8358.

4-Iodo-2-methoxy-3-(4-methoxyphenyl)-5-ferrocenyl-5H-1,2-oxaphosphole 2-Oxide (2e)

Yield: 102 mg (74%); yellow solid; dr = 1:1; R_f = 0.50 (petroleum ether/EtOAc = 5:1); mp 137–138 °C.

IR (neat): 2921, 2849, 1608, 1508, 1461, 1298, 1255, 1180, 1106, 1037, 992, 962, 917, 868, 812, 772, 737, 539 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.64 (d, J = 8.5 Hz, 4 H), 6.96 (dd, J = 8.7, 1.9 Hz, 4 H), 5.59 (d, J = 8.1 Hz, 1 H), 5.54 (d, J = 6.6 Hz, 1 H), 4.50 (dd, J = 3.5, 1.2 Hz, 2 H), 4.42 (s, 1 H), 4.32 (s, 5 H), 4.30 (s, 5 H), 4.28–4.24 (m, 4 H), 4.23 (d, J = 1.1 Hz, 1 H), 3.87 (d, J = 11.6 Hz, 3 H), 3.84 (d, J = 0.7 Hz, 6 H), 3.80 (d, J = 11.9 Hz, 3 H).

³¹P NMR (202 MHz, CDCl₃): δ = 30.3, 29.7.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 160.4, 133.1, 132.8, 131.8, 131.6, 129.5 (dd, J _pc = 13.7, 6.0 Hz), 123.5 (d, J _pc = 11.5 Hz), 116.2 (d, J _pc = 40.0 Hz), 115.6 (d, J _pc = 40.0 Hz), 114.2 (d, J _pc = 3.1 Hz), 100.0, 84.8 (d, J _pc = 8.1 Hz), 70.6 (d, J _pc = 6.8 Hz), 69.3 (d, J _pc = 1.3 Hz), 69.0 (d, J _pc = 15.0 Hz), 67.9 (d, J _pc = 9.0 Hz), 65.0, 64.6, 55.3, 54.4 (d, J _pc = 6.25 Hz), 54.2 (d, J _pc = 6.25 Hz).

HRMS (ESI): m/z [M]⁺ calcd for C₂₁H₂₀FeIO₄P: 549.9488; found: 549.9499.

3-([1,1′-Biphenyl]-4-yl)-4-iodo-2-methoxy-5-ferrocenyl-5H-1,2-oxaphosphole 2-Oxide (2f)

Yield: 102 mg (70%); yellow solid; dr = 1:1; R_f = 0.50 (petroleum ether/EtOAc = 5:1); mp 167–168 °C.

IR (neat): 2921, 2850, 1486, 1264, 1039, 994, 962, 917, 869, 806, 756, 698, 508 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.77–7.73 (m, 4 H), 7.68 (dd, J = 7.4, 0.6 Hz, 4 H), 7.64 (dd, J = 7.3, 1.2 Hz, 4 H), 7.48 (dd, J = 10.5, 4.8 Hz, 4 H), 7.43–7.36 (m, 2 H), 5.64 (d, J = 8.0 Hz, 1 H), 5.59 (d, J = 6.7 Hz, 1 H), 4.55–4.51 (m, 2 H), 4.47–4.42 (m, 1 H), 4.34 (s, 5 H), 4.33 (s, 5 H), 4.29 (d, J = 2.7 Hz, 3 H), 4.27 (dd, J = 3.9, 2.2 Hz, 1 H), 4.25 (td, J = 2.4, 1.4 Hz, 1 H), 3.92 (d, J = 11.6 Hz, 3 H), 3.86 (d, J = 11.9 Hz, 3 H).

³¹P NMR (202 MHz, CDCl₃): δ = 30.2, 29.6.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 142.1, 140.2, 130.3, 128.8, 128.4 (dd, J _pc = 12.5, 6.3 Hz), 127.7, 127.4 (d, J _pc = 3.8 Hz), 127.1, 117.7 (d, J _pc = 38.8 Hz), 117.2 (d, J _pc = 38.8 Hz), 100.0, 85.0 (d, J _pc = 7.8 Hz), 84.7, 70.7, 70.6, 69.3, 69.2, 69.1, 69.0, 68.0, 67.9, 65.0, 64.6, 54.5 (d, J _pc = 7.5 Hz), 54.3 (d, J _pc = 6.3 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₆H₂₂FeIO₃Na: 618.9593; found: 618.9554.

3-(4-(tert-Butyl)phenyl)-4-iodo-2-methoxy-5-ferrocenyl-5H-1,2-oxaphosphole 2-Oxide (2g)

Yield: 43 mg (30%); yellow solid; dr = 4:1; R_f = 0.39 (petroleum ether/EtOAc = 5:1); mp 108–109 °C.

IR (neat): 3358, 3188, 2920, 2850, 1659, 1632, 1469, 1410, 1266, 1040, 994, 869, 739, 514 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.61 (dd, J = 8.4, 1.1 Hz, 2 H), 7.45 (dd, J = 8.6, 2.7 Hz, 2 H), 5.60 (d, J = 8.0 Hz, 0.24 H), 5.55 (d, J = 6.7 Hz, 1 H), 4.52–4.49 (m, 1 H), 4.43–4.39 (m, 1 H), 4.33 (s, 5 H), 4.31 (s, 1 H), 4.29–4.27 (m, 1 H), 4.24 (d, J = 1.3 Hz, 1 H), 3.90 (d, J = 11.6 Hz, 0.77 H), 3.83 (d, J = 12.0 Hz, 3 H), 1.35 (s, 11 H).

³¹P NMR (202 MHz, CDCl₃): δ = 30.2, 29.6.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 152.5, 127.6 (dd, J _pc = 10.0, 5.0 Hz), 125.7 (d, J _pc = 4.6 Hz), 84.8, 70.7 (d, J _pc = 13.7 Hz), 69.3, 69.1, 69.0, 67.9 (d, J _pc = 7.8 Hz), 65.0, 64.6, 54.5, 54.2, 34.8, 31.2.

HRMS (ESI): m/z [M + K]⁺ calcd for C₂₄H₂₆FeIO₃PK: 614.9645; found: 614.9621.

3-(3,5-Dimethylphenyl)-4-iodo-2-methoxy-5-ferrocenyl-5H-1,2-oxaphosphole 2-Oxide (2h)

Yield: 31 mg (23%); yellow solid; >99:1 dr; R_f = 0.40 (petroleum ether/EtOAc = 5:1); mp 95–96 °C.

IR (neat): 2920, 2850, 1658, 1633, 1603, 1469, 1256, 1047, 1035, 993, 919, 832, 737, 699, 629, 505 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.21 (s, 2 H), 7.06 (s, 1 H), 5.60 (d, J = 7.9 Hz, 1 H), 4.58–4.46 (m, 1 H), 4.33 (s, 1 H), 4.32 (s, 5 H), 4.29–4.26 (m, 2 H), 3.88 (d, J = 11.6 Hz, 3 H), 2.36 (s, 6 H).

³¹P NMR (202 MHz, CDCl₃): δ = 30.2.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 138.4, 131.0, 125.6 (d, J _pc = 6.3 Hz), 117.5, 84.8, 70.6, 69.3, 68.9, 67.9, 65.0, 64.5, 54.5 (t, J _pc = 6.3 Hz), 21.3.

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₂H₂₃FeIO₃P: 548.9773; found: 548.9751.

3-Ethyl-4-iodo-2-methoxy-5-ferrocenyl-5H-1,2-oxaphosphole 2-Oxide (2i)

Yield: 69 mg (56%); yellow oil; dr = 1:1; R_f = 0.53 (petroleum ether/EtOAc = 5:1).

IR (neat): 2923, 2851, 1607, 1460, 1254, 1182, 1106, 1041, 989, 950, 918, 866, 816, 791, 740, 576 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 5.47 (d, J = 7.4 Hz, 1 H), 5.41 (d, J = 5.9 Hz, 1 H), 4.44 (s, 2 H), 4.29 (t, J = 7.4 Hz, 10 H), 4.26–4.19 (m, 4 H), 4.17 (s, 1 H), 3.97 (d, J = 11.6 Hz, 3 H), 3.86 (d, J = 11.9 Hz, 3 H), 2.46–2.24 (m, 4 H), 1.20 (t, J = 7.6 Hz, 6 H).

³¹P NMR (202 MHz, CDCl₃): δ = 32.6, 32.0.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 100.0, 84.8 (d, J _pc = 42.9 Hz), 84.5, 84.2 (dd, J _pc = 10.0, 5.0 Hz), 70.4, 70.1, 69.2, 68.9 (d, J _pc = 12.4 Hz), 67.8 (d, J _pc = 1.3 Hz), 64.8 (d, J _pc = 12.4 Hz), 64.5, 53.8 (d, J _pc = 7.5 Hz), 53.6 (d, J _pc = 6.3 Hz), 24.6 (d, J _pc = 11.7 Hz), 11.8.

HRMS (ESI): m/z [M + K]⁺ calcd for C₁₆H₁₈FeIO₃PK: 510.9019; found: 510.9020.

5-(4-(4-Chlorobenzyl)ferrocenyl)-4-iodo-2-methoxy-3-phenyl-5H-1,2-oxaphosphole 2-Oxide (2j)

Yield: 103 mg, 68%; yellow solid; >99:1 dr; R_f = 0.50 (petroleum ether/EtOAc = 5:1); mp 155–156 °C.

IR (neat): 2921, 2850, 1632, 1595, 1471, 1258, 1039, 993, 961, 916, 867, 807, 740, 697, 532 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.66–7.61 (m, 2 H), 7.45 (d, J = 7.1 Hz, 3 H), 7.24–7.16 (m, 3 H), 7.10 (d, J = 7.5 Hz, 1 H), 5.52 (d, J = 6.7 Hz, 1 H), 4.47–4.44 (m, 1 H), 4.38 (d, J = 1.1 Hz, 1 H), 4.29 (ddd, J = 6.0, 3.7, 1.7 Hz, 3 H), 4.26–4.23 (m, 2 H), 4.20 (d, J = 1.2 Hz, 1 H), 3.83 (d, J = 11.9 Hz, 3 H), 3.77 (d, J = 21.7 Hz, 2 H).

³¹P NMR (202 MHz, CDCl₃): δ = 29.6.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 143.7, 129.4 (d, J _pc = 20.3 Hz), 128.8, 128.3 (d, J _pc = 62.8 Hz), 128.0, 126.4 (d, J _pc = 60.7 Hz), 118.2 (d, J _pc = 37.5 Hz), 100.0, 88.3, 84.8 (d, J _pc = 7.5 Hz), 71.1, 70.1, 69.9, 69.7, 69.1 (d, J _pc = 10.0 Hz), 68.7 (d, J _pc = 17.5 Hz), 68.5, 65.8, 65.3, 54.2, 53.4, 35.4.

HRMS (ESI): m/z [M]⁺ calcd for C₂₇H₂₃ClFeIO₃P: 643.9462; found: 643.9439.

4-Iodo-2-methoxy-3,5-diphenyl-5H-1,2-oxaphosphole 2-Oxide (4a)

Yield: 86 mg, 76%; white solid; dr = 1:1; R_f = 0.50 (petroleum ether/EtOAc = 5:1); mp 134–135 °C.

IR (neat): 2953, 2921, 2850, 1491, 1456, 1254, 1043, 963, 865, 807, 752, 697 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.77–7.68 (m, 4 H), 7.50–7.43 (m, 16 H), 5.83 (d, J = 6.9 Hz, 1 H), 5.78 (d, J = 5.8 Hz, 1 H), 3.85 (d, J = 11.6 Hz, 3 H), 3.82 (d, J = 11.9 Hz, 3 H).

³¹P NMR (202 MHz, CDCl₃): δ = 30.8, 30.7.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 136.1, 135.7 (d, J _pc = 2.5 Hz), 135.5 (d, J _pc = 2.5 Hz), 134.8, 134.1, 131.5 (dd, J _pc = 22.0, 11.3 Hz), 129.8 (d, J _pc = 2.6 Hz), 129.6 (d, J _pc = 4.0 Hz), 128.9 (t, J _pc = 5.6 Hz), 128.2 (d, J _pc = 8.8 Hz), 128.0 (dd, J _pc = 6.3, 2.5 Hz), 116.5 (d, J _pc = 38.8 Hz), 115.7 (d, J _pc = 40.0 Hz), 87.4 (dd, J _pc = 6.9, 4.3 Hz), 54.7 (d, J _pc = 6.8 Hz), 54.3 (d, J _pc = 6.8 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₆H₁₄IO₃PNa: 434.9618; found: 434.9599.

4-Iodo-2-methoxy-3-phenyl-5-(p-tolyl)-5H-1,2-oxaphosphole 2-Oxide (4b)

Yield: 88 mg (77%); white solid; dr = 1:1; R_f = 0.48 (petroleum ether/EtOAc = 5:1); mp 176–177 °C.

IR (neat): 2920, 2850, 1490, 1444, 1253, 1183, 1043, 962, 869, 803, 776, 757, 697, 566 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.73 (t, J = 6.7 Hz, 4 H), 7.52–7.42 (m, 6 H), 7.37 (d, J = 7.6 Hz, 2 H), 7.32 (d, J = 7.7 Hz, 2 H), 7.29–7.22 (m, 4 H), 5.80 (d, J = 6.9 Hz, 1 H), 5.75 (d, J = 5.8 Hz, 1 H), 3.81 (t, J = 12.0 Hz, 6 H), 2.40 (d, J = 8.9 Hz, 6 H).

³¹P NMR (202 MHz, CDCl₃): δ = 30.7, 30.6.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 139.9 (d, J _pc = 6.6 Hz), 132.5, 129.6 (t, J _pc = 10.4 Hz), 128.9, 128.1 (dd, J _pc = 14.5, 9.5 Hz), 87.3 (t, J _pc = 7.1 Hz), 54.2 (d, J _pc = 6.8 Hz), 21.4.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₇H₁₆IO₃PNa: 448.9774; found: 448.9747.

4-Iodo-2-methoxy-5-(4-methoxyphenyl)-3-phenyl-5H-1,2-oxaphosphole 2-Oxide (4c)

Yield: 95 mg (80%); white solid; dr = 1:1; R_f = 0.52 (petroleum ether/EtOAc = 5:1); mp 144–145 °C.

IR (neat): 2921, 2849, 1611, 1587, 1515, 1461, 1248, 1177, 1043, 962, 869, 831, 806, 777, 758, 736, 697, 528 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.72 (t, J = 7.7 Hz, 4 H), 7.46 (d, J = 7.2 Hz, 6 H), 7.39 (d, J = 8.5 Hz, 2 H), 7.34 (d, J = 8.5 Hz, 2 H), 6.96 (t, J = 9.1 Hz, 4 H), 5.78 (d, J = 6.9 Hz, 1 H), 5.74 (d, J = 5.8 Hz, 1 H), 3.85 - 3.82 (m, 6 H), 3.79 (dd, J = 12.2, 4.9 Hz, 6 H).

³¹P NMR (202 MHz, CDCl₃): δ = 30.6, 30.5.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 160.7, 131.5 (dd, J _pc = 22.7, 11.3 Hz), 129.6 (dd, J _pc = 19.0, 8.1 Hz), 128.9, 128.1 (d, J _pc = 5.7 Hz), 127.7, 127.5, 114.3 (d, J _pc = 12.0 Hz), 87.1 (t, J _pc = 6.3 Hz), 55.3 (d, J _pc = 1.3 Hz), 54.6 (d, J _pc = 6.8 Hz), 54.2 (d, J _pc = 6.8 Hz).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₁₇IO₄P: 442.9904; found: 442.9918.

5-(4-(Dimethylamino)phenyl)-4-iodo-2-methoxy-3-phenyl-5H-1,2-oxaphosphole 2-Oxide (4d)

Yield: 57 mg (47%); white solid; dr = 1:1; R_f = 0.50 (petroleum ether/EtOAc = 5:1); mp 172–173 °C.

IR (neat): 2921, 2850, 1612, 1527, 1362, 1255, 1187, 1040, 950, 869, 803, 759, 696 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.77–7.69 (m, 4 H), 7.51–7.43 (m, 6 H), 7.32–7.24 (m, 4 H), 6.75 (t, J = 9.0 Hz, 4 H), 5.78 (d, J = 7.0 Hz, 1 H), 5.72 (d, J = 5.9 Hz, 1 H), 3.79 (dd, J = 11.8, 7.4 Hz, 6 H), 3.01 (d, J = 8.5 Hz, 12 H).

³¹P NMR (202 MHz, CDCl₃): δ = 30.4, 30.2.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 151.4 (d, J _pc = 2.7 Hz), 131.8 (dd, J _pc = 23.1, 11.1 Hz), 129.4, 129.3 (d, J _pc = 5.0 Hz), 129.2, 128.8, 128.1 (d, J _pc = 5.7 Hz), 122.4 (d, J _pc = 12.8 Hz), 112.1 (d, J _pc = 6.2 Hz), 87.9 (dd, J _pc = 13.8, 6.6 Hz), 54.4 (d, J _pc = 6.8 Hz), 54.1 (d, J _pc = 6.7 Hz), 40.3 (d, J _pc = 1.8 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₈H₁₉INO₃PNa: 478.0009; found: 478.0016.

5-(4-Bromophenyl)-4-iodo-2-methoxy-3-phenyl-5H-1,2-oxaphosphole 2-Oxide (4e)

Yield: 60 mg (62%); white solid; >99:1 dr; R_f = 0.40 (petroleum ether/EtOAc = 5:1); mp 162–163 °C.

IR (neat): 2922, 2851, 1593, 1488, 1264, 1182, 1038, 980, 868, 802, 774, 755, 696, 515 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.71 (dd, J = 6.3, 1.4 Hz, 2 H), 7.59 (d, J = 8.4 Hz, 2 H), 7.48 (d, J = 6.5 Hz, 3 H), 7.38 (d, J = 8.4 Hz, 2 H), 5.74 (d, J = 5.8 Hz, 1 H), 3.82 (d, J = 12.0 Hz, 3 H).

³¹P NMR (202 MHz, CDCl₃): δ = 30.8.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 135.7, 134.9 (dd, J _pc = 76.2, 73.4 Hz), 134.6 (t, J _pc = 6.7 Hz), 132.1 (d, J _pc = 12.6 Hz), 129.7 (d, J _pc = 14.2 Hz), 128.9, 128.0 (d, J _pc = 5.8 Hz), 115.6 (d, J _pc = 38.6 Hz), 86.5 (d, J _pc = 7.2 Hz), 54.4 (d, J _pc = 6.8 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₆H₁₃BrIO₃PNa: 512.8723; found: 512.8690.

5-(3-Hydroxyphenyl)-4-iodo-2-methoxy-3-phenyl-5H-1,2-oxaphosphole 2-Oxide (4f)

Yield: 24 mg (21%); white solid; dr = 2:1; R_f = 0.46 (petroleum ether/EtOAc = 5:1); mp 102–103 °C.

IR (neat): 3189, 2920, 2850, 1736, 1646, 1591, 1469, 1422, 1233, 1048, 967, 869, 811, 778, 758, 695 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.67 (ddd, J = 7.2, 4.5, 1.6 Hz, 3 H), 7.49–7.44 (m, 2 H), 7.45–7.39 (m, 3 H), 7.31–7.23 (m, 3 H), 7.03 (d, J = 1.8 Hz, 1 H), 7.01–6.89 (m, 4 H), 5.73 (d, J = 6.3 Hz, 1 H), 5.65 (d, J = 6.6 Hz, 0.56 H), 3.81 (d, J = 12.0 Hz, 5 H).

³¹P NMR (202 MHz, CDCl₃): δ = 31.2, 31.1.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 157.2, 156.8, 136.4, 131.1, 130.1, 129.9, 129.6, 128.9, 128.0 (dd, J _pc = 10.3, 5.7 Hz), 120.5, 119.8, 117.5, 117.1, 115.6, 114.2, 87.6 (d, J _pc = 6.8 Hz), 54.8, 54.5 (d, J _pc = 7.0 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₆H₁₄IO₄PNa: 450.9567; found: 450.9537.

5-(2-Chlorophenyl)-4-iodo-2-methoxy-3-phenyl-5H-1,2-oxaphosphole 2-Oxide (4g)

Yield: 20 mg (17%); white solid; >99:1 dr; R_f = 0.52 (petroleum ether/EtOAc = 5:1); mp 156–157 °C.

IR (neat): 2921, 2850, 1592, 1490, 1443, 1258, 1046, 990, 965, 872, 859, 807, 754, 696 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.77–7.70 (m, 2 H), 7.53–7.46 (m, 5 H), 7.41–7.35 (m, 2 H), 6.46 (s, 1 H), 3.83 (d, J = 12.0 Hz, 3 H).

³¹P NMR (202 MHz, CDCl₃): δ = 30.9.

¹³C {¹H} NMR (125 MHz, CDCl₃): δ = 136.0, 134.7, 133.4, 130.9, 129.7 (d, J _pc = 18.0 Hz), 128.9, 128.0 (d, J _pc = 6.3 Hz), 127.9, 114.6, 114.3, 54.3 (d, J _pc = 6.8 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₆H₁₄ClIO₃PNa: 468.9228; found: 468.9250.

4-Iodo-2-methoxy-3-phenyl-5-(thiophen-3-yl)-5H-1,2-oxaphosphole 2-Oxide (4h)

Yield: 60 mg (53%); white solid; dr = 1:1; R_f = 0.38 (petroleum ether/EtOAc = 5:1); mp 109–110 °C.

IR (neat): 2921, 2850, 1590, 1491, 1444, 1255, 1042, 992, 961, 921, 868, 758, 696, 539 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.70 (dd, J = 11.6, 4.6 Hz, 4 H), 7.53–7.45 (m, 8 H), 7.39 (ddd, J = 12.1, 5.0, 3.0 Hz, 2 H), 7.22–7.18 (m, 1 H), 7.14–7.11 (m, 1 H), 5.94 (d, J = 7.9 Hz, 1 H), 5.90 (d, J = 6.5 Hz, 1 H), 3.81 (d, J = 10.0 Hz, 3 H), 3.79 (d, J = 10.3 Hz, 3 H).

³¹P NMR (202 MHz, CDCl₃): δ = 30.7, 30.6.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 136.7 (d, J _pc = 6.9 Hz), 129.6 (d, J _pc = 2.5 Hz), 128.9, 128.0 (t, J _pc = 5.9 Hz), 127.1 (d, J _pc = 8.7 Hz), 126.6, 126.4, 126.0 (d, J _pc = 17.9 Hz), 82.9 (dd, J _pc = 15.5, 7.7 Hz), 54.5 (d, J _pc = 6.8 Hz), 54.3 (d, J _pc = 6.8 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₄H₁₂IO₃PSNa: 440.9182; found: 440.9149.

5-(Cyclohex-1-en-1-yl)-4-iodo-2-methoxy-3-phenyl-5H-1,2-oxaphosphole 2-Oxide (4i)

Yield: 76 mg (67%); white solid; dr = 3:1; R_f = 0.47 (petroleum ether/EtOAc = 5:1); mp 143–144 °C.

IR (neat): 2921, 2850, 1632, 1469, 1289, 1253, 1180, 1043, 961, 922, 876, 837, 804, 776, 756, 697, 534 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.68–7.64 (m, 2 H), 7.64–7.61 (m, 1 H), 7.43 (q, J = 5.8 Hz, 4 H), 6.03 (s, 1.4 H), 5.20 (d, J = 6.1 Hz, 0.38 H), 5.17 (d, J = 5.6 Hz, 1 H), 3.77 (d, J = 11.6 Hz, 1 H), 3.71 (d, J = 12.0 Hz, 3 H), 2.15 (d, J = 2.7 Hz, 4 H), 1.77–1.53 (m, 7 H).

³¹P NMR (202 MHz, CDCl₃): δ = 30.4, 30.3.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 137.2, 136.6, 136.0, 135.4, 133.6, 133.5 (d, J _pc = 1.3 Hz), 132.6 (d, J _pc = 2.5 Hz), 131.9 (d, J _pc = 11.3 Hz), 131.7 (d, J _pc = 11.3 Hz), 129.4 (d, J _pc = 11.6 Hz), 128.8, 127.9 (d, J _pc = 5.8 Hz), 116.5 (d, J _pc = 38.8 Hz), 116.3 (d, J _pc = 5.8 Hz), 90.7 (dd, J _pc = 14.1, 5.9 Hz), 54.5 (d, J _pc = 6.7 Hz), 54.0 (d, J _pc = 6.8 Hz), 25.4 (d, J _pc = 3.7 Hz), 22.1 (d, J _pc = 28.8 Hz), 22.0 (d, J _pc = 10.0 Hz), 21.9, 21.7, 21.3.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₆H₁₈IO₃PNa: 438.9931; found: 438.9916.

5-Hexyl-4-iodo-2-methoxy-3-phenyl-5H-1,2-oxaphosphole 2-Oxide (4j)

Yield: 58 mg (63%); yellow oil; >99:1 dr; R_f = 0.36 (petroleum ether/EtOAc = 5:1).

IR (neat): 2925, 2855, 1590, 1490, 1256, 1036, 957, 802, 754, 695 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.62 (d, J = 6.8 Hz, 2 H), 7.42 (t, J = 6.8 Hz, 3 H), 4.93 (dd, J = 8.0, 2.7 Hz, 1 H), 3.72 (t, J = 11.0 Hz, 3 H), 2.24–2.09 (m, 1 H), 1.91–1.65 (m, 1 H), 1.51–1.20 (m, 8 H), 0.91 (q, J = 6.9 Hz, 3 H).

³¹P NMR (202 MHz, CDCl₃): δ = 30.2.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 136.0 (d, J _pc = 20.0 Hz), 134.7 (d, J _pc = 17.8 Hz), 131.8 (dd, J _pc = 15.6, 11.3 Hz), 129.3 (d, J _pc = 2.9 Hz), 128.8 (d, J _pc = 1.3 Hz), 128.7, 128.6, 128.3 (d, J _pc = 3.8 Hz), 128.0 (dd, J _pc = 7.4, 5.7 Hz), 116.6 (d, J _pc = 5.7 Hz), 116.3 (d, J _pc = 5.9 Hz), 85.4 (dd, J _pc = 8.0, 6.3 Hz), 54.3 (d, J _pc = 6.7 Hz), 54.1 (d, J _pc = 6.7 Hz), 34.5, 34.3, 31.6 (d, J _pc = 2.1 Hz), 28.8 (d, J _pc = 4.7 Hz), 24.1, 23.6, 22.6 (d, J _pc = 1.8 Hz), 14.1.

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₆H₂₃IO₃P: 421.0424; found: 421.0420.

4-Iodo-2-methoxy-3-(4-methoxyphenyl)-5-phenyl-5H-1,2-oxaphosphole 2-Oxide (4k)

Yield: 76 mg (86%); white solid; dr = 1:1; R_f = 0.52 (petroleum ether/EtOAc = 5:1); mp 140 °C.

IR (neat): 2921, 2849, 1611, 1515, 1461, 1248, 1177, 1043, 962, 869, 831, 806, 758, 697 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.74 (ddd, J = 14.2, 8.7, 1.1 Hz, 4 H), 7.47 (dt, J = 4.7, 3.2 Hz, 2 H), 7.45–7.40 (m, 8 H), 6.99 (d, J = 8.7 Hz, 4 H), 5.79 (d, J = 7.1 Hz, 1 H), 5.75 (d, J = 5.7 Hz, 1 H), 3.84 (d, J = 1.8 Hz, 6 H), 3.82 (d, J = 11.6 Hz, 3 H), 3.78 (d, J = 12.0 Hz, 3 H).

³¹P NMR (202 MHz, CDCl₃): δ = 31.1, 31.0.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 160.6 (d, J _pc = 4.7 Hz), 135.8 (dd, J _pc = 32.8, 2.1 Hz), 135.7 (d, J _pc = 2.7 Hz), 135.2, 134.4, 133.9, 133.2, 129.8 (d, J _pc = 1.5 Hz), 129.5 (dd, J _pc = 6.0, 1.2 Hz), 128.9 (d, J _pc = 12.2 Hz), 128.3 (d, J _pc = 8.6 Hz), 123.4 (dd, J _pc = 27.7, 11.6 Hz), 114.5, 114.3, 114.2, 113.8, 113.5, 87.3 (dd, J _pc = 7.0, 3.4 Hz), 55.4, 54.6 (d, J _pc = 6.8 Hz), 54.2 (d, J _pc = 6.8 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₇H₁₆IO₄PNa: 464.9723; found: 464.9695.

3-([1,1′-Biphenyl]-4-yl)-4-iodo-2-methoxy-5-phenyl-5H-1,2-oxaphosphole 2-Oxide (4l)

Yield: 101 mg (80%); white solid; dr = 1:1; R_f = 0.50 (petroleum ether/EtOAc = 5:1); mp 174–175 °C.

IR (neat): 2920, 2850, 1485, 1457, 1254, 1041, 963, 867, 839, 762, 752, 698 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.86 (t, J = 9.6 Hz, 4 H), 7.72 (d, J = 8.0 Hz, 4 H), 7.66 (d, J = 6.9 Hz, 4 H), 7.53–7.44 (m, 14 H), 7.41 (t, J = 7.2 Hz, 2 H), 5.85 (d, J = 6.9 Hz, 1 H), 5.80 (d, J = 5.7 Hz, 1 H), 3.87 (dd, J = 17.1, 11.9 Hz, 6 H).

³¹P NMR (202 MHz, CDCl₃): δ = 40.0, 30.9.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 142.4 (d, J _pc = 7.9 Hz), 140.2, 135.8, 135.2 (d, J _pc = 86.7 Hz), 133.7, 129.9, 128.9 (t, J _pc = 5.5 Hz), 128.4 (dd, J _pc = 25.8, 7.4 Hz), 127.9, 127.6, 127.2, 116.1 (d, J _pc = 38.8 Hz), 115.4 (d, J _pc = 38.8 Hz), 116.2, 115.7 (d, J _pc = 51.8 Hz), 115.2, 87.5 (d, J _pc = 6.6 Hz), 54.7 (d, J _pc = 6.8 Hz), 54.3 (d, J _pc = 6.8 Hz).

HRMS (ESI): m/z [M + K]⁺ calcd for C₂₂H₁₈IO₃PK: 526.9670; found: 526.9663.

3-(4-(tert-Butyl)phenyl)-4-iodo-2-methoxy-5-phenyl-5H-1,2-oxaphosphole 2-Oxide (4m)

Yield: 74 mg (60%); white solid; >99:1 dr; R_f = 0.42 (petroleum ether/EtOAc = 5:1); mp 170–171 °C.

IR (neat): 2959, 2921, 2850, 1457, 1291, 1263, 1046, 989, 966, 866, 757, 698, 507 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.72 (dd, J = 8.4, 1.3 Hz, 2 H), 7.49 (dd, J = 9.0, 5.1 Hz, 4 H), 7.44 (dd, J = 5.0, 2.1 Hz, 3 H), 5.77 (d, J = 5.8 Hz, 1 H), 3.82 (d, J = 12.0 Hz, 3 H), 1.37 (s, 9 H).

³¹P NMR (202 MHz, CDCl₃): δ = 31.1.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 152.8, 135.7 (d, J _pc = 2.6 Hz), 129.8, 128.8, 128.2, 127.7 (d, J _pc = 6.0 Hz), 125.8, 87.4 (d, J _pc = 6.8 Hz), 54.2 (d, J _pc = 6.8 Hz), 34.9, 31.2.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₀H₂₂IO₃PNa: 491.0244; found: 491.0222.

3-(4-Fluorophenyl)-4-iodo-2-methoxy-5-phenyl-5H-1,2-oxaphosphole 2-Oxide (4n)

Yield: 88 mg (76%); white solid; dr = 2:1; R_f = 0.50 (petroleum ether/EtOAc = 5:1); mp 180–181 °C.

IR (neat): 2920, 2850, 1595, 1505, 1457, 1256, 1159, 1039, 965, 862, 756, 700 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.78–7.69 (m, 3 H), 7.50–7.40 (m, 8 H), 7.18 (t, J = 8.6 Hz, 3 H), 5.82 (d, J = 7.1 Hz, 0.57 H), 5.77 (d, J = 5.7 Hz, 1 H), 3.83 (dd, J = 16.0, 11.8 Hz, 5 H).

³¹P NMR (202 MHz, CDCl₃): δ = 30.6, 30.5.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 164.3, 162.3, 135.6, 135.4 (d, J _pc = 2.8 Hz), 135.1, 134.5, 133.9, 133.3, 130.1 (dd, J _pc = 8.4, 5.9 Hz), 129.9, 128.9 (d, J _pc = 10.7 Hz), 128.2 (d, J _pc = 8.1 Hz), 127.4, 116.8, 116.5, 116.2, 116.0, 87.3 (dd, J _pc = 6.8, 3.1 Hz), 54.7 (d, J _pc = 6.9 Hz), 54.3 (d, J _pc = 6.8 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₆H₁₃FIO₃PNa: 452.9523; found: 452.9501.

3-(4-Chlorophenyl)-4-iodo-2-methoxy-5-phenyl-5H-1,2-oxaphosphole 2-Oxide (4o)

Yield: 83 mg (70%); white solid; dr = 1:1; R_f = 0.48 (petroleum ether/EtOAc = 5:1); mp 177–178 °C.

IR (neat): 2921, 2850, 1586, 1488, 1456, 1253, 1092, 1045, 987, 964, 867, 834, 756, 739, 698 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.69 (dd, J = 10.0, 8.8 Hz, 4 H), 7.47 (dt, J = 10.4, 3.0 Hz, 12 H), 7.42 (dd, J = 6.6, 3.0 Hz, 2 H), 5.82 (d, J = 7.0 Hz, 1 H), 5.77 (d, J = 5.7 Hz, 1 H), 3.86 (d, J = 11.6 Hz, 3 H), 3.83 (d, J = 11.9 Hz, 3 H).

³¹P NMR (202 MHz, CDCl₃): δ = 30.5, 30.4.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 135.7, 135.3, 134.5, 133.3, 129.9 (d, J _pc = 6.0 Hz), 129.8, 129.4 (d, J _pc = 5.7 Hz), 129.2, 129.0 (d, J _pc = 10.7 Hz), 128.2 (d, J _pc = 7.2 Hz), 117.3, 117.0, 87.4 (d, J _pc = 6.5 Hz), 54.7 (d, J _pc = 6.9 Hz), 54.4 (d, J _pc = 6.8 Hz).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₆H₁₄ClIO₃P: 446.9408; found: 446.9411.

3-(4-Bromophenyl)-4-iodo-2-methoxy-5-phenyl-5H-1,2-oxaphosphole 2-Oxide (4p)

Yield: 65 mg (66%); white solid; >99:1 dr; R_f = 0.49 (petroleum ether/EtOAc = 5:1); mp 190–191 °C.

IR (neat): 2921, 2851, 1484, 1264, 1044, 1012, 964, 865, 829, 804, 756, 698 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.63 (s, 4 H), 7.50–7.44 (m, 5 H), 5.76 (d, J = 5.8 Hz, 1 H), 3.82 (d, J = 11.9 Hz, 3 H).

³¹P NMR (202 MHz, CDCl₃): δ = 30.3.

¹³C{¹H} NMR (125 MHz, CDCl₃): δ = 135.2, 133.4, 132.2, 130.4, 129.9, 129.6 (d, J _pc = 5.8 Hz), 128.91, 128.2, 124.0, 117.3, 117.0, 87.4 (d, J _pc = 6.4 Hz), 54.4 (d, J _pc = 6.8 Hz).

HRMS (ESI): m/z [M]⁺ calcd for C₁₆H₁₃BrIO₃P: 489.8825; found: 489.8829.

4-Iodo-2-methoxy-3-methyl-5-phenyl-5H-1,2-oxaphosphole 2-Oxide (4q)

Yield: 45 mg (44%); white solid; >99:1 dr; R_f = 0.38 (petroleum ether/EtOAc = 5:1); mp 147–148 °C.

IR (neat): 2953, 2850, 1616, 1457, 1253, 1185, 1044, 967, 863, 806, 753, 700 cm^–1.

¹H NMR (500 MHz, CDCl₃): δ = 7.40 (td, J = 5.2, 2.6 Hz, 3 H), 7.35–7.29 (m, 2 H), 5.71–5.63 (m, 1 H), 3.90 (d, J = 11.6 Hz, 3 H), 2.05 (dd, J = 13.6, 2.0 Hz, 3 H).

³¹P NMR (202 MHz, CDCl₃): δ = 33.7.

¹³C{¹H}NMR (125 MHz, CDCl₃): δ = 135.6 (d, J _pc = 1.9 Hz), 132.8, 131.6, 129.7 (d, J _pc = 4.6 Hz), 128.8 (d, J _pc = 7.7 Hz), 128.1, 127.9, 117.5, 117.2, 87.0 (d, J _pc = 7.4 Hz), 54.3 (d, J _pc = 6.8 Hz), 15.9 (d, J _pc = 12.5 Hz).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₁H₁₃IO₃P: 350.9642; found: 350.9642.

Electrophilic Cyclization of Ferrocene-Containing Allenylphosphonate 1a with PhSeCl; General Procedure

To a solution of ferrocene-containing allenylphosphonate 1a (0.20 mmol) in CH₃CN/H₂O (20:1; 3.0 mL) was added PhSeCl (0.24 mmol) under a N₂ atmosphere. The resulting mixture was cooled to 0 °C and stirred for 5 hours. After completion of the reaction, the solvent was removed in vacuum, and the resulting residue was purified on a silica gel column (petroleum ether/EtOAc = 5:1) to afford the yellow solid product 5 (see the Supporting Information).

2-Methoxy-5-ferrocenyl-3-phenyl-4-(phenylselanyl)-5H-1,2-oxaphosphole 2-Oxide (5)

Yield: 66 mg (66%); yellow solid; R_f = 0.50 (petroleum ether/EtOAc = 3:1); mp 206 °C.

IR (neat): 2924, 2841, 2097, 1589, 1469, 1246, 1192, 1111, 999, 918, 756 cm^–1.

¹H NMR (500 MHz, DMSO-d ₆): δ = 7.39 (s, 5 H), 7.30 (d, J = 7.1 Hz, 3 H), 7.28–7.21 (m, 2 H), 5.72 (d, J = 9.4 Hz, 1 H), 4.35–4.16 (m, 7 H), 4.14 (s, 1 H), 3.95 (s, 1 H), 3.75 (d, J = 12.4 Hz, 3 H).

³¹P NMR (202 MHz, DMSO): δ = 33.7.

¹³C NMR (125 MHz, DMSO): δ = 150.8, 134.4, 131.3 (d, J _pc = 12.3 Hz), 129.9, 129.2, 129.01, 128.4 (d, J _pc = 6.2 Hz), 126.6, 86.5, 81.5 (d, J _pc = 7.8 Hz), 69.6, 69.4, 68.9, 67.9, 65.2, 54.3 (d, J _pc = 6.6 Hz), 40.2, 40.0, 39.8.

HRMS (ESI): m/z [M]⁺ calcd for C₂₆H₂₄FeO₃PSe: 550.9974; found: 551.0000.

Conflict of Interest

The authors declare no conflict of interest.

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• 11 The structure of 5 was confirmed by X-ray diffraction analysis of the single crystal; see the Supporting Information. CCDC 2100153 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures

Corresponding Author

Publication History

Received: 10 December 2021

Accepted after revision: 19 April 2022

Accepted Manuscript online:
19 April 2022

Article published online:
09 June 2022

© 2022. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

• References

• 1a Stewart JD, Liotta LJ, Benkovic SJ. Acc. Chem. Res. 1993; 26: 396
  CrossrefSearch in Google Scholar
• 1b Racha S, Vargeese C, Vemishetti P, El-Subbagh HI, Abushanab E, Panzica RP. J. Med. Chem. 1996; 39: 1130
  CrossrefPubMedSearch in Google Scholar
• 1c Moonen K, Laureyn I, Stevens CV. Chem. Rev. 2004; 104: 6177
  Search in Google Scholar
• 1d Chen L, Liu XY, Zou YX. Adv. Synth. Catal. 2020; 362: 1724
  CrossrefSearch in Google Scholar
• 2 De Clercq E. Biochem. Pharmacol. 2007; 73: 911
  CrossrefPubMedSearch in Google Scholar
• 3 Bekro YA, Pirat JL, Virieux D. Tetrahedron 2016; 72: 7912
  CrossrefSearch in Google Scholar
• 4a Ma SM. Acc. Chem. Res. 2009; 42: 1679
  CrossrefPubMedSearch in Google Scholar
• 4b Berton JK. E. T, Heugebaert TS. A, Virieux D, Stevens CV. Chem. Eur. J. 2017; 23: 17413
  CrossrefPubMedSearch in Google Scholar
• 4c Swamy KC. K, Anitha M, Debnath S, Shankar M. Pure Appl. Chem. 2019; 91: 773
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For selected examples, see:
• 5a Macomber RS. J. Org. Chem. 1978; 43: 1832
  CrossrefSearch in Google Scholar
• 5b Macomber RS, Krudy GA, Seff K, Rendon-Diaz-Miron LE. J. Org. Chem. 1983; 48: 1425
  CrossrefSearch in Google Scholar
• 5c Yu F, Lian XD, Zhao JB, Yu YH, Ma SM. J. Org. Chem. 2009; 74: 1130
  CrossrefPubMedSearch in Google Scholar
• 5d Xin N, Ma SM. Eur. J. Org. Chem. 2012; 3806
  Crossref
• 5e Li P, Liu Z.-J, Liu J.-T. Tetrahedron 2010; 66: 9729
  CrossrefSearch in Google Scholar
• 5f Yu F, Lian XD, Ma SM. Org. Lett. 2007; 9: 1703
  CrossrefPubMedSearch in Google Scholar
• 5g Fourgeaud P, Midrier C, Vors J.-P, Volle J.-N, Pirat J.-L, Virieux D. Tetrahedron 2010; 66: 758
  CrossrefSearch in Google Scholar
• 5h Essid I, Laborde C, Legros F, Touil S, Rolland M, Ayad T, Volle J.-N, Pirat J.-L, Virieux D, Sevrain N. Org. Lett. 2017; 19: 1882
  CrossrefPubMedSearch in Google Scholar
• 5i Berton JK. E. T, Salemi H, Pirat J.-L, Virieux D, Stevens CV. J. Org. Chem. 2017; 82: 12439
  CrossrefPubMedSearch in Google Scholar
• 6 Kealy TJ, Pauson PL. Nature 1951; 168: 1039
  CrossrefSearch in Google Scholar
• 7a Fu GC. Acc. Chem. Res. 2004; 37: 542
  CrossrefPubMedSearch in Google Scholar
• 7b Fu GC. Acc. Chem. Res. 2006; 39: 853
  CrossrefPubMedSearch in Google Scholar
• 7c Horikoshi R. Coord. Chem. Rev. 2013; 257: 621
  CrossrefSearch in Google Scholar
• 7d Dai L.-X, Tu T, You S.-L, Deng W.-P, Hou X.-L. Acc. Chem. Res. 2003; 36: 659
  CrossrefPubMedSearch in Google Scholar
• 7e Colacot TJ. Chem. Rev. 2003; 103: 3101
  CrossrefPubMedSearch in Google Scholar
• 7f Hudson SA, Maitlis PM. Chem. Rev. 1993; 93: 861
  CrossrefSearch in Google Scholar
• 7g Fabre B. Acc. Chem. Res. 2010; 43: 1509
  CrossrefPubMedSearch in Google Scholar
• 7h van Staveren DR, Metzler-Nolte N. Chem. Rev. 2004; 104: 5931
  CrossrefPubMedSearch in Google Scholar
• 7i Fouda MF. R, Abd-Elzaher MM, Abdelsamaia RA, Labib AA. Appl. Organomet. Chem. 2007; 21: 613
  CrossrefSearch in Google Scholar
• 7j Hartinger CG, Dyson P. Chem. Soc. Rev. 2009; 38: 391
  CrossrefPubMedSearch in Google Scholar
• 7k Braga SS, Silva AM. S. Organometallics 2013; 32: 5626
  CrossrefSearch in Google Scholar
• 7l Moriuchi T, Hirao T. Acc. Chem. Res. 2010; 43: 1040
  CrossrefPubMedSearch in Google Scholar
• 8a Biot C, Dive D. Top. Organomet. Chem. 2010; 32: 155
  Search in Google Scholar
• 8b Hillard EA, Vessieres A, Jaouen G. Top. Organomet. Chem. 2010; 32: 81
  Search in Google Scholar
• 8c Ornelas C. New J. Chem. 2011; 35: 1973
  CrossrefSearch in Google Scholar
• 9a Guo L, Zhao W, Li M, Dong S, Gong J, Chen S. Appl. Organomet. Chem. 2019; 33: e5003
  CrossrefSearch in Google Scholar
• 9b Guo L, Gao Y, Wang Z, Li Z, Zhang Y, Wang H, Chen X, Gong Z, Chen S. J. Org. Chem. 2020; 85: 7358
  CrossrefPubMedSearch in Google Scholar
• 10 The structure of 2a was confirmed by X-ray diffraction analysis of the single crystal; see the Supporting Information. CCDC 2060581 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
• 11 The structure of 5 was confirmed by X-ray diffraction analysis of the single crystal; see the Supporting Information. CCDC 2100153 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures

• Supplementary Material