Highly Efficient Asymmetric Conjugate Additions of Aldehydes with Vinyl Sulfones Using a Sulfonamide Organocatalyst

Abstract

A sulfonamide organocatalyst promotes the asymmetric conjugate addition of branched aldehydes to vinyl sulfones to afford the corresponding adducts with all-carbon quaternary stereocenters in excellent yields with up to 95% ee.

Key words

organocatalyst - conjugate addition - sulfonamide - vinyl sulfone - quaternary stereocenter

• References and Notes


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• 7 Typical Procedure for the Michael Additions Using 6 To a solution of 10a (30.8 mg, 0.100 mmol) and organocatalyst 6 (3.8 mg, 0.010 mmol) in m-xylene (1.0 mL) was added 2-phenylpropanal (26.8 μL, 0.200 mmol) and TFA (0.7 μL, 0.010 mmol) at r.t. After stirring at r.t. for 2 h, the reaction mixture was directly purified by flash column chromatography on silica gel with a 3:1 mixture of hexane and EtOAc to afford the pure 11a ⁴ (42.0 mg, 95%) as a colorless powder; [α]_D ¹⁸ –25.6 (c 1.00, CHCl₃); 95% ee; the ee was determined by HPLC with a Chiralpak AS-H column (hexane–2-PrOH = 70:30), flow rate = 1.0 mL/min; λ = 220 nm; t _R (major) = 21.7 min, t _R (minor) = 25.9 min. ¹H NMR (400 MHz, CDCl₃): δ = 1.46 (s, 3 H), 2.82 (dd, J = 5.8, 16.4 Hz, 1 H), 2.95 (dd, J = 3.4, 16.4 Hz, 1 H), 4.42 (dd, J = 3.4, 5.8 Hz, 1 H), 7.26–7.29 (m, 2 H), 7.36–7.73 (m, 11 H), 7.87 (d, J = 8.2 Hz, 2 H), 9.60 (s, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 19.6, 30.9, 53.1, 80.2, 127.6, 128.1, 129.1, 129.3, 129.7, 129.8, 134.6, 137.3, 137.8, 138.3, 201.4