Methyltrichlorosilane-DMSO: A Facile and Highly Efficient Recipe for the Chlorination of Enamides and Enecarbamates

Abstract

A facile and highly efficient method was developed for the chlorination of enamides and enecarbamates with the combined use of methyltrichlorosilane and DMSO, which allowed one-pot production of the corresponding β-chloro enamides and enecarbamates in high yield and good stereoselectivity. This method is easy to operate and suitable for both cyclic and acyclic substrates.

MeSiCl₃-DMSO - enamides - enecarbamates - chlorination - stereoselectivity

References and Notes

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General Procedure for the Chlorination of Enamides and Enecarbamtes
To a solution of enamide or enecarbamte (0.1 mmol) in CH₂Cl₂ (1 mL) was added DMSO (0.15 mmol) and chlorosilane (0.2 mmol). After stirring at r.t. for 1 h, the reaction solution was quenched by sat. aq NaHCO₃ (1 mL). The resulting mixture was extracted with EtOAc (3 ¥ 5 mL). The combined organic layer was washed with brine (3 ¥ 5 mL), dried over MgSO₄, and concentrated under reduced pressure. The residue was purified through column chromatography on silica gel to give the desired β-chlorinated enamide or enecarbamate.

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Spectroscopic Data for ( Z )-2b and 2h Compound (Z)-2b: ^¹H NMR (300 MHz, CDCl₃): δ = 7.40-7.30 (m, 8 H), 7.20 (s, 2 H), 6.70 (s, 1 H), 5.00 (s, 2 H), 2.09 (s, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 153.3, 135.8, 135.0, 131.5, 128.9, 128.4, 128.2, 128.1, 128.0, 118.6,
67.1, 21.9; mp 80-82 ˚C. ESI-HRMS: m/z calcd for C₁₇H₁₆ClNO₂Na: 324.0767; found: 324.0762.
Compound 2h: ^¹H NMR (300 MHz, CDCl₃): δ = 7.24-7.11 (m, 4 H), 6.06 (s, 1 H), 4.19 (q, J = 7.1 Hz, 2 H), 2.96 (t, J = 8.0 Hz, 2 H), 2.72 (t, J = 8.0 Hz, 2 H), 1.28 (t, J = 5.7 Hz, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 154.4, 134.1, 131.6, 128.9, 127.9, 127.5, 127.3, 126.5, 122.9, 61.6, 31.4, 28.3, 14.4; mp 175-178 ˚C. ESI-HRMS: m/z calcd for C₁₃H₁₄ClNO₂Na: 274.0611; found: 274.0605.

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It should be noted that the hydrogen bonding in A2 may not be very important since an N-methylated substrate 1l (Figure  [¹] ) was also found to undergo smooth chlorination under identical conditions, albeit with lower yield (79%) and stereoselectivity (Z/E = 4:1).

Figure 1

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As pointed out by one referee, another possible pathway via a direct attack of the enamide on the choro of a chloro-dimethylsulfonium intermediate could not be excluded, see:

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