Triple asymmetric induction

The stereoselectivity of the aldol additions shown in Schemes 5.25 and 5.26 are obviously the result of a complex series of factors, among which are the Felkin-Anh preference dictated by the a-substituent on the aldehyde, the proximal stereocenters on the enolate, etc. Additionally, the more remote stereocenters, such as at the p-position of the aldehyde, may influence the selectivity of these types of reactions. Evans has begun an investigation into some of the more subtle effects on crossed aldol selectivity, such as protecting groups at a remote site on the enolate [131], and of P-substituents on the aldehyde component [132], and also of matched and mismatched stereocenters at the a and P positions of an aldehyde (double asymmetric induction) [133]. Further, the effect of chiral enolates adding to a,P-disubstituted aldehydes has been evaluated [134]. The latter turns out to be a case of triple asymmetric induction, with three possible outcomes fully matched, partially matched, and one fully mismatched trio. 

This reaction is mediated by (+)-diisopinocampheylboron chloride [(+)-DIP-Cl)] and produces the aldol product in good yield with reasonable selectivity. This is the first case in which this reagent system has been used successfully in a triple asymmetric induction situation to achieve the desired stereocontrol in a mismatched aldol coupling. 

The butynoate 14 adds to the chiral enone 3 from the a-surface with asymmetric induction probably rationalized by the chelate model 15. The initial product 16 of the 1,4-conjugate addition is capable of another intramolecular Michael addition to the triple bond resulting in conversion of 16 to 4. 

A wide variety of tandem, triple [12], and even quadruple [13, 14] cyclizations can be performed with multiply unsaturated 1,3-dicarbonyl compounds as shown in Eq. (1) [14] this provide intermediates for steroid and terpene syntheses. High levels of asymmetric induction can be achieved with phenylmenthyl acetoacetate... 

The final approach was elegantly presented by Panek [44]. Several optically active ( )-crotylsilanes are available via stereoselective Ireland-Claisen rearrangement of enantiomerically pure vinylsilanes. Addition of the chiral crotylsilanes to acetals or to mixtures of aldehyde and trimethylsilyl methyl ether is effected by la to afford homoallylic ethers in exceedingly high diastereo- and enantioselectivity (Sch. 13). Occasionally a stoichiometric amount of la is required for allylation of aliphatic acetals, preserving the excellent level of asymmetric induction. The synthesis of (-F)-macbecin I involving triple use of the strategy imderscores the utility of the la-catalyzed asymmetric allylation [44c]. 

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