Pair-selective aldol reaction

A pair-selective aldol reaction proved to be possible and is illustrated in Eq. (25) from the four starting materials, only two products were obtained [100], This clearly indicates that the coupling of the ketene silyl acetal and acetophenone and that of the enol silyl ether and benzaldehyde dimethylacetal are very favorable paths, whereas the reactions of other combinations are not. A similar phenomenon is illustrated by Eq. (26) [100]. 

Unusual -branched Baylis-Hillman adducts have been prepared by Li and coworkers by a novel Et2AlCl promoted domino Michael-aldol reaction of propynoates 50 with organo-cuprates and chiral p-toluenesulfinimines 52 (Scheme 10) [42], These condensations proceeded with very good diastereoselectivity to give allylic amines 53. The selectivity can be explained through the chairlike transition state 54. The anion intermediate approaches the sulfinimine from the sterically less hindered side of the lone pair of electrons. The nucleo-... 

These aldols have all had just one chiral centre in the starting material. Should there be more than one, double diastereomeric induction produces matched and mismatched pairs of substrates and reagents, perfectly illustrated by the Evans aldol method applied to the syn and anti aldol products 205 themselves derived from asymmetric aldol reactions. The extra chiral centre, though carrying just a methyl group, has a big effect on the result. The absolute stereochemistry of the OPMB group is the same in both anti-205 and yvn-205 but the stereoselectivity achieved is very different. The matched case favours Felkin selectivity as well as transition state 201 but, with the mismatched pair, the two are at cross purposes. It is interesting than 1,2-control does not dominate in this case.33... 

Since the stereochemical outcome of the aldol reaction with these enolates is predictable from the above results, selection of either (5)-(29b) or (R)-(29b) for a matched or mismatched pair can easily be made. Thus, in the reaction of chiral aldehyde (24) with (5)-(29b) (matched) the product ratio exceeds 1(X) 1, favoring formation of (33), whereas when reagent (R)-(29b) is used, (34) l omes the predominant product with a respectable stereoselection (mismatched) (Scheme 24). Compared to the ratios observed for the reaction with an achiral enolate (Scheme 22), it is clear that the facial selectivity of the enolates dictates the 3,4-stereochemistry of the aldol reaction and either the 2,3-jy -3,4-an or 2,3-syn-3,4-syn units can be constructed in a predictable manner. 

Independent work on asymmetric aldol reactions by Evans et al. led to the development of alternative chiral boron enolates that exhibit >100 1 facial selectivity. A pair of chiral N-acyl-2-oxazolidones (35)... 

Paterson et have prepared the enolate of 3-pentanone, an achiral ketone, with (-( )- or (-)-IpcaBOTf and have found that its aldol reactions with various aldehydes proceed with high syn.anti ratios (>9 1) and respectable enantioselectivities (5 1-20 1) (Scheme 44). High degrees of asymmetric induction are noted with unhindered aldehydes, llie combination of the chiral ethyl ketone (104) and (-t-)-Ipc2BOTf constitutes a matched pair, which enhances the diastereofacial selectivity of the resulting enolate (compared to that obtained with an achiral boron reagent), and provides via aldol reactions high... 

Su, Z., Mariano, P.S., Falvey, D.E., Yoon, U.C,. and Oh, S.W, Dynamics of anihnium radical a-heterolytic fragmentation processes. Electrofugal group, substituent and medium effects on desi-lylation, decarboxylation and retro-Aldol cleavage pathways, /. Am. Chem. Soc., 120, 10676,1998. Hasegawa, E., Xu, W, Mariano, P.S., Yoon, U.C., and Kim, J.U., Electron transfer induced photoadditions of the silylamine EtjNCHjTMS to a,P-unsaturated cyclohexenones. Dual reaction pathways based on ion pair selective cation radical chemistry, /. Am. Chem. Soc., 110, 8099, 1988. Yoon, U.C., Kim, J.U., Hasegawa, E., and Mariano, P.S., Electron transfer photochemistry of a-silylamine cyclohexenone systems. Medium effects on reaction pathways followed, /. Am. Chem. Soc., 109, 4421,1987. 

---