The direct cross‐aldol reaction of alkynyl aldehydes catalyzed by a trifluoromethylated diarylprolinol provides a practical route for the highly enantioselective synthesis of chiral β‐alkynyl‐β‐hydroxy aldehydes. Good anti selectivity and excellent enantioselectivity were obtained in the reactions of silylpropynals, which afford synthetically useful chiral building blocks.

Synthetic methods: An asymmetric catalytic, desulfonylative Mannich reaction of α-keto imines with aldehydes, as catalyzed by diarylprolinol silyl ether 1, was developed. It gave the Mannich product in good yield with excellent anti and enantioselectivity (see scheme; Boc = tert-butoxycarbonyl, TMS = trimethylsilyl).

The asymmetric cross-aldol reaction of α,α-disubstituted acetaldehydes with commercial ethyl glyoxylate polymer was successfully catalyzed by diphenylprolinol silyl ether 3The aldol reaction is one of the most useful carbon-carbon bond forming reactions in organic chemistry.[1] After the pioneering discovery of the intermolecular proline-mediated aldol reaction of aldehydes and ketones by List, Lerner and Barbas in 2000, there has been great progress in the field of organocatalysed asymmetric aldol chemistry.[2]The cross aldol reaction of two different aldehydes catalyzed by proline was reported by MacMillan in 2002.[3] Although the generated β-hydroxy aldehydes are synthetically useful and versatile chiral building blocks, the reaction is often limited to particular aldehydes. Our group has continuing interest to develop a general organocatalyst for the asymmetric cross-aldol reaction of aldehydes. Through our efforts, we have found trifluoromethyl-substituted diarylprolinol as an effective organocatalyst in the aldol reaction of not only acetaldehyde as the pro-nucleophile, [4] but also ethyl glyoxylate, [5] chloroacetaldehye, [6] trifluoroacetaldehyde ethyl acetal, [7] pyruvaldehyde, [8] succinaldehyde, [9] glyoxal, [10] alkynyl aldehyde, [11] and formaldehyde [12] as the electrophilic aldehyde.An equally continuing challenge for contemporary synthetic organic chemistry is the asymmetric synthesis of allcarbon quaternary stereogenic centers. [13] In this context, there have been only two reports, as far as we are aware, that describe the intermolecular asymmetric aldol reaction to form all-carbon quaternary stereogenic centers. Tanaka [a]

Asymmetric Aldol Reaction of ,-Disubstituted Acetaldehydes Catalyzed by Diphenylprolinol Silyl Ether for the Construction of Quaternary Stereogenic Centers. -The aldol reaction of aldehydes (I) and (V) with ethyl glyoxylate polymer affords the corresponding aldol adducts with moderate diastereoselectivities and low to good enantioselectivities. -(HAYASHI*, Y.; SHOMURA, H.; XU, Q.; LEAR, M. J.; SATO, I.; Eur. J. Org. Chem. 2015, 20, 4316-4319, http://dx.doi.org/10.1002/ejoc.201500585 ; Dep. Chem., Grad. Sch. Sci., Tohoku Univ., Aoba, Sendai 980, Japan; Eng.) -Mais 47-024