The Ireland–Claisen rearrangement as a probe for the diastereoselectivity of nucleophilic attack on a double bond adjacent to a stereogenic centre carrying a silyl group

Abstract

The E- and Z-silyl enol ethers 4 derived from allyl 3-R-3-dimethyl(phenyl)silylpropanoate (R = Me, Pr(i) and Ph) and the Z-silyl enol ethers 7 derived from 4-R-4-dimethyl(phenyl)silylbut-2-enyl acetate (R = Me and Pr(i)) undergo Ireland-Claisen rearrangements largely in the same stereochemical sense, with C-C bond formation taking place anti to the silyl group in the conformations 22, 23 and 24 in which the hydrogen atom on the stereogenic centre is inside, more or less eclipsing the double bond. The E-silyl enol ether E-7a derived from 4-methyl-4-dimethyl(phenyl)silylbut-2-enyl acetate shows low diastereoselectivity in the alternative sense, probably because C-C bond formation takes place anti to the silyl group in the conformation 26 with the methyl group inside, but the silyl enol ether E-7b derived from 4-isopropyl-4-dimethyl(phenyl)silylbut-2-enyl acetate shows low diastereoselectivity in the normal sense. The E- and Z-silyl enol ethers 33 derived from cis-crotyl 3-phenyl-3-dimethyl(phenyl)silylpropanoate and the E-silyl enol ether 39 derived from trans-crotyl 3-phenyl-3-dimethyl(phenyl)silylpropanoate undergo Ireland-Claisen rearrangements largely in the same stereochemical sense as their allyl counterparts, but with moderately high levels of diastereocontrol in setting up the third stereogenic centre following from chair-like transition structures.

Diastereocontrol in open-chain nucleophilic attack on a double bond adjacent to a stereogenic centre carrying a silyl group

“…6 Using a more rigid system, described in the first paper of this series, 7 we have shown that a dialkylcuprate adds predominantly (96 : 4) to the enone 6 from above, as drawn, again anti to the silyl group, and have suggested that the silyl group, held axially in the cyclohexanone ring, substantially blocks the lower surface. Finally, in some Ireland-Claisen rearrangements described in the immediately preceding paper, 8 we have again seen attack anti to the silyl group, whether the electronic bias was that of nucleophilic attack 7 (98 : 2) or electrophilic attack 8 (86 : 14), where it was notable that the higher of the ratios of diastereoisomers was in the nucleophilic attack series 7.…”

New Electrophiles for the Catalytic, Asymmetric "Interrupted" Feist-Bénary Reaction

“…Our initial results showed substantially different enantioselectivities for the IFB reactions of 1,5-diester (12) and 1,4-diketo (19) substrates with the same chiral catalyst. In the presence of catalytic QN-6 in methylene chloride, IFB product 14 was that the steric properties of the phenyl group are likely not responsible for the decrease in stereocontrol.…”

“…Work by Fleming et al on the stereocontrolled Ireland-Claisen rearrangement (Scheme 2) demonstrates how one might use a starting material's chirality to generate additional stereocenters. 19 In this reaction, a bulky dimethyl(phenyl)silyl group attached to a stereogenic carbon directs attack anti to itself to afford a 93:7 ratio between the two diastereomeric products. Fleming et al rationalize this stereospecificity through an analysis of the transition state geometry ( Fig.…”

“…7), which shows H pointing up to avoid unfavorable 1,3-allylic strain and attack preferentially occurring from the less hindered methyl face. 19 By utilizing a series of highly stereocontrolled reactions on an enantioenriched starting material, chemists have been able to synthesize a wide range of complex chiral molecules. Using only the stereochemistry provided by commercially available (-)-quinic acid, the Hanessian group was able to synthesize enantiopure (+)-palitantin ( Fig.…”

“…76,78 isolation of the dihydrofuran intermediate. 87,90 Much of the synthetic importance of this reaction stems from the one (R 1 = H) or two (R 1 ≠ H) stereocenters created in the uneliminated product (Scheme 19). An enantio-and diastereoselective version of the IFB reaction thus permits the synthesis of highly substituted, chiral hydroxydihydrofuranoids from relatively simple achiral or racemic starting materials.…”