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...