Asymmetric cyanohydrin synthesis using an aluminium(salan) complex

The asymmetric addition of trimethylsilyl cyanide to aldehydes catalysed by chiral metal(salan) complexes has been investigated. Salan complexes of titanium and vanadium displayed only low catalytic activity, but a bimetallic aluminium(salan) complex gave high levels of catalytic activity and reasonable asymmetric induction when used with triphenylphosphine oxide as a cocatalyst. Mechanistic studies showed that the reactions were first order in catalyst and aldehyde concentrations, but zero order in trimethylsilyl cyanide and triphenylphosphine oxide concentrations. A Hammett analysis indicated that there was no significant change in the electron density at the aldehyde benzylic position during the rate determining step of the catalytic cycle. On the basis of the kinetic data, a catalytic cycle is proposed which accounts for the differences observed between [Al(salen)]2O and [Al(salan)]2O based catalysts.

Figure optionsDownload as PowerPoint slide

(N,N′-((3,5-di-tert-Butyl-2-hydroxyphenyl)methyl)(1R,2R)-1,2-diaminocyclohexane)vanadiumoxy chlorideC36H56N2O3VClEe = 100%[α]D = +1680 (c 0.01, CHCl3)Source of chirality: resolved 1,2-diaminocyclohexaneAbsolute configuration: (1R,2R)

Bis-[(N,N′-((3,5-di-tert-butyl-2-hydroxyphenyl)methyl)(1R,2R)-1,2-diaminocyclohexane)aluminium] oxideC72H112Al2N4O5Ee = 100%[α]D = +14.8 (c 1.0, CHCl3)Source of chirality: resolved 1,2-diaminocyclohexaneAbsolute configuration: (1R,2R)