Catalytic Asymmetric Cyanoethoxycarbonylation of Aldehydes Using Self-Assembled Titanium Catalysts

Abstract

A new self-assembled titanium catalyst system has been developed for the asymmetric cyanoethoxycarbonylation of aldehydes which produced the desired products in moderate to excellent yields (up to 99%) with high enantioselectivities (up to 94% ee) under mild conditions. The catalyst was readily prepared from tetra­isopropyl titanate [Ti(Oi-Pr)₄], a Schiff base, and cinchonine.

Key words

asymmetric catalysis - cyanation - aldehydes - self-­assembly - titanium

References and Notes

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10

The result of hydrogenated tridentate Schiff base 1b was only 50% ee, maybe due to its more flexible framework.

11

THF: 35 h, 83% yield, 35% ee; Et₂O: 48 h, 70% yield, 76% ee; toluene: 30 h, 90% yield, 31% ee; CHCl₃: 15 h, 90% yield, 52% ee; ClCH₂CH₂Cl: 15 h, 84% yield, 23% ee.

12

Zr(Oi-Pr)₄: 24 h, 80% yield, 72% ee; Al(Oi-Pr)₃: 10 h, 90% yield, 7% ee; Zr(OEt)₄: 48 h, 84% yield, 30% ee; Cu(OTf)₂, 48 h, no reaction.

13

General Procedure for the Asymmetric Cyanoethoxy-carbonylation of Aldehydes: To a solution of 1b (0.0125 mmol, 4.0 mg) and 2a (0.0125 mmol, 3.7 mg) in CH₂Cl₂ (125 µL) was added Ti(Oi-Pr)₄ (1.0 M in toluene, 0.0125 mmol, 12.5 µL) at r.t., and then the mixture was stirred at 30 °C for 0.3 h under an argon atmosphere. To this solution, the corresponding aldehyde (0.25 mmol) was added, and then EtOCOCN (1.5 equiv) was added after 10 min at -20 °C under the argon atmosphere. After stirring for another 2.5 h, the crude product was purified by column chromatography on silica gel (PE-Et₂O, 10:1) to give the corresponding cyanohydrin carbonates.