Binolam-AlCl: A Two-Centre Catalyst for the Synthesis of Enantioenriched Cyanohydrin O-Phosphates

The enantioselective synthesis of cyanohydrin O‐phosphates by using in situ generated bifunctional catalysts (R)‐ or (S)‐3,3′‐bis(diethylaminomethyl)‐1,1′‐binaphthol–aluminium chloride (binolam–AlCl) is reported. The reaction, which can be described as an overall cyano‐O‐phosphorylation of aldehydes, has a wide scope and applicability. Evidence is also provided, including ab initio and DFT calculations, in support of supported by the Lewis acid/Brønsted base (LABB) dual role of the catalyst in inducing first the key enantioselective hydrocyanation, which is then followed by O‐phosphorylation. A brief screening of the synthetic usefulness of the resulting cyanohydrin O‐phosphates unveiles some interesting applications. Among them, chemoselective hydrolysis, reduction and palladium‐catalysed nucleophilic allyl substitution, thereby leading to enantiomerically enriched α‐O‐phosphorylated α‐hydroxy esters, β‐amino alcohols and γ‐cyanoallyl alcohols, respectively. Naturally occurring (−)‐tembamide and (−)‐aegeline are synthesised accordingly. A bifunctional catalytic system consisting of a binolam–AlCl two‐centre catalyst for the synthesis of enantioenriched cyanohydrin O‐phosphates is described (see scheme). The catalyst is based on a Lewis base–Lewis acid (LBLA) monometallic aluminium complex, which is involved in the hydrocyanation–phosphorylation sequence. The experiments were also supported by DFT calculations. Synthetic applications of the chiral cyanophosphates have been found.