D. A. Evans Bonding considerations: Carbon vs Silicon Chem 206 Carbonyl addition Reactions The prospect of catalysis was investigated 1970 DAE Objective: Develop a reagent that will transform aldehydes into protected cyanohydrins in one step Me3Si-CN 1-5 min OSiMe3 reaction was instaneous and quantitative OSiR3 1-5 min i Principle established that normally inaccessible cyanohydrin derivatives G=carbanion-stabilizing FG Carbonyl Anion Equivalent may now be accessed TMSO CN >95% yield R3Si-G Candidates Carbonyl Adducts only 1, 2-addition OSiR3 95%ye R,Si-CN with Truesdale, Carroll, Chem Commun. 1973, 55: J. Org. Chem. 1974, 39, 914 Tetrahedron Lett 1973, 4929(first discussion of Nu catalysis) OSiR R3Si-OSO,Ar R- The Silicon Advantage From the preceding case, it is clear that AHs is more exothermic than AHH R3Si-OPR R-tPOR2 X XcN一 Hsi>AH Thermalc=o addition of mscn is not a clean reaction Nucleophilic Catalysis e3SI-CN OSiMe ato:65:35D. A. Evans Bonding Considerations: Carbon vs Silicon Chem 206 Carbonyl addition Reactions 1970 DAE Objective: Develop a reagent that will transform aldehydes into protected cyanohydrins in one step R H O SiR3 G + R G OSiR3 H R G OSiR3 Li R3Si G Candidates Carbonyl Adducts R3Si CN R CN OSiR3 H R3Si OSO2Ar R SO2Ar OSiR3 H R3Si OPR2 R POR2 OSiR3 H G = carbanion-stabilizing FG Carbonyl Anion Equivalent Thermal C=O addition of TMSCN is not a clean reaction + Me3Si CN C5H11 H OSiMe3 CN 50 C° Me H O C4H9 H OSiMe3 + ratio: 65:35 2-5 hr The prospect of catalysis was investigated C5H11 H OSiMe3 CN 1-5 min ZnI2 reaction was instaneous and quantiltative 1-5 min CN– Principle established that normally inaccessible cyanohydrin derivatives may now be accessed Me Me Me OTMS CN >95% yield (ZnI2 catalysis) Me Me TMSO Me CN 92% yield only 1,2-addition (ZnI2 catalysis) O TMSO CN >95% yield only 1,2-addition (CN– catalysis) with Truesdale, Carroll, Chem Commun. 1973, 55; J. Org. Chem.. 1974, 39, 914 Tetrahedron Lett 1973, 4929 (first discussion of Nu catalysis) + Me3Si CN Me H O "The Silicon Advantage" R R O + X CN R R O–X CN DHSi > DHH From the preceding case, it is clear that DHSi is more exothermic than DHH R R O Nucleophilic Catalysis C N R R O CN Me3Si CN R R OTMS CN C N + LiNR2