Felkin—Ahn selectivity

The major isomer is assigned the 3R, 4S stereochemistry on the expectation that the addition would occur preferentially with Cram (Felkin-Ahn) selectivity.3 This assignment was confirmed by 1H NMR DNOE experiments on the isobutyraldehyde acetal. 

In practice, aldehydes bearing an adjacent stereogenic center, particularly one devoid of a bulky group, typically provide only modest aldol stereoselectivity. For example, consider the reaction of aldehyde 28 with Z boron enolate 27 as shown in Scheme 3a. According to the models just discussed, one would expect this reaction to provide only 1,2-syn products with anti-Felkin- Ahn stereoselectivity. Indeed, that conjecture proved to be true for the most part as exclusively 1,2-syn aldol adducts resulted with 29, a compound whose stereotriad reflected anti-Felkin—Ahn selectivity, constituting the predominant product. However, a fair amount of the alternate 1,2-syn Felkin- Ahn adduct (30) was also observed, such that the final ratio of 29 to 30 was a disappointing 1.75 1. 

This allylation protocol was used in the total synthesis of amphidinolide to give homoallylic alcohol 12 in 72% yield and 17 1 dr (eq 5). Initial transmetallation of stannane 10 with (R,R)-1 via allylic transposition yielded an intermediate borane. Introduction of aldehyde 11 at -78 °C provided for a facile condensation reaction leading to 12. Stereocontrol was induced from the 1,2-diphenylethane sulfonamide auxiliary and could be predicted from a Zimmerman-Traxler model with minimized steric repulsions. The high level of selectivity obtained in this case was a result of a matched diastereomeric transition state featuring the inherent Felkin-Ahn selectivity for nucleophilic attack in aldehyde 11, with the (5)-configuration of the benzoate of 10, as well as the (7 ,7 -antipode of auxiliary 1, resulting in threefold stereodifferentiation. 

Radical addition to conjugated systems is an important part of chain propagation reactions. The rate constants for addition of cyclohexyl radical to conjugated amides have been measured, and shown to be faster than addition to styrene. In additions to RCH=C(CN)2 systems, where the R group has a chiral center, the Felkin-Ahn rule (p. 148) is followed and the reaction proceeds with high selectivity. Addition of some radicals, such as (McsSijaSi-, is reversible and this can lead to poor selectivity or isomerization. ... 

Sterically bulky OR groups (trityloxy or Bu PtbSiO) gave tlie yyn-diastereoisomer (119) either exclusively or predominantly. The, vv -selectivity was rationalized by a modified Felkin-Ahn model (121).94... 

High yields and enantiopurity have been realized by a highly diastereoselective MPV reduction of protected a-amino aromatic ketones using catalytic amounts of aluminium isopropoxide. The high anti selectivity resulted from the chelation of the (g) nitrogen anion to the aluminium. In contrast, high syn selectivity was obtained with a-alkoxy ketones and other compounds via Felkin-Ahn control.354... 

The Cram selectivity is consistent with Felkin-Ahn addition, as shown in Figure 8a, with the large phenyl substituent controlling the organometallic approach. In addition, Yamamoto et a/. have proposed more detailed chair-like transition state models shown in Figures 8b and 8c to account for the un-... 

A -(a-Carboxyalkyl)tryptamines can be prepared by alkylation of a-amino acid ester by tryptophyl bromide. The chirality of the amino acid unit directs diastereo-selectivity in the range of 70-98% for cyclization with a variety of aromatic aldehydes. The best selectivity is obtained with relatively bulky amino acid substituents, as for valine and isoleucine. The reactions appear to occur under kinetic control and the stereoselectivity is consistent with the sterically preferred Felkin-Ahn transition state [336]. 

It appears that the diastereofacial selectivity may be correlated with the nature of the enolate cation and the 0-protecting group. The sodium cation, known to be a weaker Lewis acid, cannot efflciently coordinate the silyloxy group of imine especially if it is large, so that facial selectivity follows, at least in part, a Felkin-Ahn model leading to preponderant formation of the anti isomer. However, the more basic imine nitrogen atom still coordinates the sodium cation so that the simple distereoselectivity still proceeds via a closed boat-like Zimmerman-Traxel transition state leading exclusively to the formation of (raru-azetidinones (Scheme IS). 

Discuss the factors behind selection of the reactive conformation in the Felkin-Ahn model for conversion of 53 to 54. How would Cornforth have rationalized this stereochemical result [For an interesting system where the Cornforth and Felkin-Ahn models predict different stereochemical results see Evans, D. A. Siska, S. J. Cee, V. J. Resurrecting the Cornforth Model for Carbonyl Addition Studies on the Origin of 1,2-Asymmetric Induction in Enolate Additions to Heteroatom-Substituted Aldehydes Andrew. Chem. Int. Ed. 2003, 42, 1761-1765] (CJH-5)... 

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