Lewis Acid–Lewis Base‐Catalysed Enantioselective Addition of α‐Ketonitriles to Aldehydes

Abstract

Additions of structurally diverse a-ketonitriles to aromatic and aliphatic prochiral aldehydes yielding highly enantioenriched acylated cyanohydrins were achieved using a combination of a titanium salen dimer and an achiral or chiral Lewis base. In most cases high yields and high enantioselectivities were observed. The ee was moderate in the initial part of the reaction but increased over time. This could be avoided, and higher ees obtained, by keeping the titanium complex, in the presence or absence of aldehyde and ketonitrile, at À40 8C prior to the addition of the Lewis base. A mechanism initiated by nucleophilic attack of the tertiary amine at the carbonyl carbon atom of the ketonitile is supported by 13 C labelling experiments.

Synthesis of Dicarbonyl Curcumin Analogues Containing the Tropane Scaffold

“…The planned C ‐acylation of tropane derived enones called for the use of substituted cinnamoyl cyanides (vide infra). The cyanides were prepared by reacting corresponding acyl chlorides with dry copper(I) cyanide in acetonitrile (Table ) …”

Kinetics and mechanism of vanadium catalysed asymmetric cyanohydrin synthesis in propylene carbonate

“…Titanium complex 1 will catalyse the asymmetric addition of TMSCN to aromatic aldehydes with 80–90% enantiomeric excess at room temperature with just 0.1 mol % of catalyst [11]. Complex 1 also catalyses the asymmetric addition of other cyanide sources including potassium cyanide [12–15], cyanoformates [15–20] and acyl cyanides [17,19,21] to aldehydes, and will accept some ketones as substrates [22–23]. Recently, a modified version of complex 1 , in which the two salen ligands are covalently linked together has been developed which allows the amount of catalyst used to be reduced to 0.0005 mol % [24–25].…”

Mechanistic studies on the enantioselective BINOLAM/titanium(IV)-catalyzed cyanobenzoylation of aldehydes: Part 1

“…16 By analogy, the cyanide derivatives used as reagents in cyanation reactions could well be the source of HCN due to inevitable partial, or trace, hydrolysis undergone during manipulation. In previous work we, 17,18,19 and other groups, 20 22 as there were no Brønsted acids (ROH, H 2 O, etc) available neither on the catalyst, nor in the reaction medium. The main support for this proposal was the lack of incorporation of 13 C when H 13 CN was bubbled through the reaction solution prior to introduction of the reagents.…”