Possible Intervention of Prototropic and Silatropic Ene‐type Mechanisms in Asymmetric Catalytic Mukaiyama Aldol Reactions

Abstract

Dedicated to Professor Teruaki Mukaiyama on the occasion of the 40th anniversary of the Mukaiyama aldol reaction.Abstract: Prototropic and silatropic ene mechanisms were analyzed in the BINOL-Ti IV , bisoxazoline (box)-Cu II , and BINAP-Pd II complex-catalyzed asymmetric Mukaiyama aldol reaction of methyl glyoxylate and acetone-derived 2trimethylsiloxypropene. Our ab initio calculations indicate that the BINOL-Ti IV -catalyzed Mukaiyama aldol reaction proceeds through the concerted prototropic or silatropic ene pathways and that box-Cu II -and BINAP-Pd II -catalyzed reactions proceed through the stepwise prototropic ene pathways. The transition-state conformations are thus synclinal with hydrogen and silane as the migratory groups aligned to the formyl oxygen atom in close syn-clinal proximity, respectively.The aldol reaction, the addition of an enolate species to a carbonyl group, constitutes one of the most fundamental bond construction processes in organic synthesis. [1] The enol silyl ethers (ESEs) of ketones and (thio)esters can also be used as storable enolate equivalents in aldol-type processes, namely the Mukaiyama aldol reaction to give, after desilylation, b-hydroxyl carbonyl compounds, a class of synthetically and biologically important compounds (Scheme 1). [2] Therefore, the detailed understanding of the reaction mechanisms of the Mukaiyama aldol processes [1,3] and asymmetric catalysis thereof have attracted much attention. [1b-d] Four transition state (TS) conformations of the Mukaiyama aldol reactions between aldehydes and ESEs have been proposed (Scheme 2). An acyclic (open-chain) anti-periplanar transition state model (A) [4] has been wellaccepted to explain the formation of syn-diastereomers of b-hydroxyl carbonyl products, irrespective of the geometry of ESEs. In contrast, the changeover of diastereoselection from syn to anti, by changing from (Z)-to (E)-ESE can be explained by a cyclic (closed) syn-clinal transition state model. The syn-clinal transition state was classified into the metalocyclic syn-clinal B [5] or the exo-metalic cyclic synclinal B'. [6] There is also an acyclic (open-chain) syn-clinal transition state model (C) [7] that was proposed to explain the formation of the anti-diastereomer, irrespective of the geometry of ESEs; [8] acyclic allylic strain [9] and stereoelectronic [10] effects are operative in defining their s-cis pinwheel-shape conformation. [8b, 11] X-ray structure analyses showed that a propionate-derived ESE has the alkyl vinyl ether-like conformation. [12] Significantly, topological features have been reported for syn-clinal transition states in diastereoselective Michael additions of enamines to nitroolefins, which are applicable to Mukaiyama aldol reactions: [8a] 1) All bonds should be staggered. 2) A gauche arrangement could be operative between ESE C=C and aldehyde C=O and C À H bonds.3) The larger substituent of the enolate might be anti with respect to the "aldehyde" C=O bond. 4) The enolate and aldehyde oxygen atoms with developing charges shoul...

Asymmetric Electrophilic α-Amination of Silyl Enol Ether Derivatives via the Nitrosocarbonyl Hetero-ene Reaction

“…Silyl enol ethers and silyl ketene thioacetals are known to undergo asymmetric hetero-ene reactions with aldehydes. , These are commonly referred to as the Mukaiyama aldol reaction, for which a prototropic or silatropic mechanism has been invoked. Silyl enol ethers derivatives bearing allylic hydrogens are known to proceed through a prototropic mechanism, and in their absence, the silatropic pathway becomes favored. , Despite the significant potential, no asymmetric aza-variant using nitroso compounds has been developed. Herein we report an asymmetric nitrosocarbonyl hetero-ene reaction with silyl enol ether derivatives (Scheme b) …”