Convenient Synthesis of 1-(Trimethylsilyl)- and 1-(Trimethylstannyl)vinylphosphonates

Abstract Dimethyl 1,1-bis(trimethylsilyl)methylphosphonate and dimethyl 1-(trimethylsilyl)-1-(trimethylstannyl)methylphosphonate were succeeded to react with aromatic aldehydes in the presence of methyl benzoate as additive to give the corresponding vinylphosphonates in moderate yields. GRAPHICAL ABSTRACT


INTRODUCTION
Organophosphorus, organosilicon, and organotin compounds are useful intermediates for organic synthesis. Methylphosphonates with two phosphorus functional groups 1 and phosphorus and silicon functional groups 2 are actively used in organic synthesis. However, to the best our knowledge the derivatives with three functional groups are little investigated so far. So, we became interested in the reactivity of multi-functionalized methylphosphonates toward carbonyl compounds. Furthermore, the vinylphosphonates obtained are useful reagents in tandem reactions such as Michael reaction-Horner-Emmons-Woodwards reaction. 3 Here, we report on the convenient synthesis of vinylphosphonates with trimethylsilyl and trimethylstannyl groups at α-position starting from multi-functionalized methylphosphonates with trimethylsilyl and trimethylstannyl groups. In order to determine the limitation of this reaction, a similar reaction of 4a with aliphatic aldehydes and ketones was carried out. Reaction of 4a with benzophenone, acetophenone, and isobutyraldehyde did not occur because of steric hindrance and/or more acidic protons (entries 9-14). However, 4a reacted with α,β-unsaturated aldehydes such as crotonaldehyde, 4-methoxycinnamaldehyde, and pelliraldehyde in the presence of methyl benzoate or sodium fluoride to give 6i-k in 46%-81% yields (entries 15-19). These results indicate that the additive plays an important role in the activation of the silicon functional group. Methyl benzoate seems to assist the Peterson reaction through a weak interaction between silicon and oxygen. It was found that reaction of 4a with aromatic aldehydes gave predominantly the Z-form of the corresponding vinylphosphonates, while similar reaction with α,β-unsaturated aldehydes afforded mainly the E-form vinylphosphonates.
In conclusion, the multi-functionalized methylphosphonates 4a,b were useful for the synthesis of 1-(trimethylsilyl)vinylphosphonate and 1-(trimethylstannyl)vinylphosphonate. Reaction of 4a,b with aromatic aldehydes gave mainly the anti-isomers with respect to the olefinic proton and the phosphonyl group. On the other hand, reaction of 4a,b with α,βunsaturated aldehydes gave predominantly the respective syn-isomers. EXPERIMENTAL 1 H, 13 C, 29 Si, and 31 P NMR spectra were obtained with a JEOL JNM-EX400 spectrometer in CDCl3 operating at 400 MHz, 100 MHz, 79 MHz, and 160 MHz, respectively, using Me 4 Si ( 1 H, 13 C, 29 Si) and 85% H 3 PO 4 ( 31 P) as internal standards. IR spectra were recorded with a Shimadzu FTIR-8100A instrument. X-ray diffraction data were collected with a Rigaku XtaLAB mini diffractometer using graphite monochromated Mo-Kα radiation (0.71075 Å). Melting points were measured in open capillary tubes and are uncorrected. All reactions were carried out using degassed solvents under an argon atmosphere.
Tetrahydrofuran (THF) was purified by distillation over benzophenone ketyl under an argon atmosphere before use.

Preparation of Dimethyl (Trimethylsilyl)methylphosphonate (3a) and Dimethyl (Trimethylstannyl)methylphosphonate (3b)
A solution of dimethyl methylphosphonate 1 (12.4 g, 100 mmol) in THF (40 mL) was added slowly to n-BuLi (1.65 M in hexane, 65.6 mL, 100 mmol) in THF (65 mL) at −70 • C under argon atmosphere. After stirring for 15 min at the same temperature copper (I) iodide (20.0 g, 100 mmol) was added to the mixture. The reaction mixture was warmed to −35 • C and was stirred at −35 • C for 1 h. A solution of 2a,b (100 mmol) in THF (30 mL) was added to the mixture at −35 • C. The reaction mixture was stirred for 12 h and was quenched by the addition of water (100 mL). The mixture was filtered on celite pad, extracted with diethyl ether and the organic layer was dried over anhydrous magnesium sulfate. The solvent was removed in vacuo and the residue was distilled under reduced pressure to give 3a,b.

Preparation of Dimethyl Bis(trimethylsilyl)methylphosphonate (4a) and Dimethyl (Trimethylsilyl)(trimethylstannyl)methylphosphonate (4b)
To a solution of diisopropylamine (15.3 g, 90 mmol) in THF (120 mL) was added n-BuLi (1.65 M in hexane, 125 mL, 90 mmol) at −70 • C under argon atmosphere. After stirring for 15 min at the same temperature, a solution of 3a,b (90 mmol) in THF (40 mL) was added to the mixture. After stirring for 15 min at the same temperature chlorotrimethylsilane (14.8 mL, 90 mmol) was added to the mixture. The reaction mixture was warmed to −35 • C and stirring was continued at −35 • C for 1 h. The reaction mixture was stirred for 12 h at room temperature and was quenched by addition of 2 M hydrochloric acid. The mixture was extracted with diethyl ether and the organic layer was dried over anhydrous magnesium sulfate. The solvent was removed in vacuo and the residue was purified by vacuum distillation or column chromatography on silica gel (chloroform:diethyl ether = 1:1) to give 4a,b.

Reaction of 4a with Carbonyl Compounds 5a-k: General Procedure
To a solution of diisopropylamine (0.7 mL, 5.0 mmol) in THF (5 mL) was added n-BuLi (1.65 M in hexane, 3 mL, 5.0 mmol) at −70 • C under argon atmosphere. After stirring for 15 min at the same temperature, a solution of 4a (0.54 g, 2.0 mmol) in THF (5 mL) was added to the mixture. After stirring for 15 min at the same temperature, a solution of the respective carbonyl compound 5a-k (4 mmol) in THF (5 mL) was added to the mixture. After stirring for 15 min at the same temperature, the additive (methyl benzoate (0.41 g, 3.0 mmol) or sodium fluoride (0.10 g, 2.4 mmol)) was added to the mixture in one portion. The reaction mixture was allowed to warm to room temperature and stirring was continued for 12 h. The reaction mixture was quenched by the addition of 2M hydrochloric acid. The mixture was extracted with diethyl ether and the organic layer was dried over anhydrous magnesium sulfate. The solvent was removed in vacuo and the residue was chromatographed on preparative TLC (ethyl acetate:hexane = 2:3) to give compounds 6a-k. The results are summarized in Table 1.

Michael Addition and Peterson Tandem Reaction of 6d
To a solution of 1-bromo-3,4,5-trimethoxybenzene (0.08 g, 0.3 mmol) in THF (3 mL) was added n-BuLi (1.65 M in hexane, 0.2 mL, 0.3 mmol) at −70 • C under argon atmosphere. After stirring for 15 min at the same temperature a solution of 6e (0.10 g, 0.3 mmol) in THF (3 mL) was added to the mixture. After being stirring for further 15 min at the same temperature a solution of crotonaldehyde (0.03 g, 0.4 mmol) in THF (2 mL) was added to the mixture. The reaction mixture was warmed to room temperature and stirring was continued for 2 h. The reaction mixture was quenched by the addition of 2 M hydrochloric acid. The mixture was extracted with diethyl ether and the organic layer was dried over anhydrous magnesium sulfate. The solvent was removed in vacuo and the residue was chromatographed on preparative TLC (ethyl acetate:hexane = 2:3) to give 0.05 g of compound 7 (34% yield).

Reaction of 4b With Carbonyl Compounds 5a,b,j
To a solution of diisopropylamine (0.7 mL, 5.0 mmol) in THF (5 mL) was added n-BuLi (1.65 M in hexane, 3 mL, 5.0 mmol) at −70 • C under argon atmosphere. After stirring for 15 min at the same temperature a solution of 4b (0.72 g, 2.0 mmol) in THF (5 mL) was added to the mixture. After stirring for further 15 min at the same temperature a solution of the respective carbonyl compound 5a,b,j (4.0 mmol) in THF (5 mL) was added to the mixture and stirring was continued for 15 min at the same temperature. Sodium fluoride (0.10 g, 2.4 mmol) was added to the mixture one portion. The reaction mixture was warmed to room temperature and stirring was continued for 12 h. The reaction mixture was quenched by the addition of 2 M hydrochloric acid. The mixture was extracted with diethyl ether and the organic layer was dried over anhydrous magnesium sulfate. The solvent was removed in vacuo, and the residue was chromatographed on preparative TLC (chloroform:diethyl ether = 9:1) to give compounds 8a,b,j.