The use of chiral (salen)TiCl2 complexes to induce the asymmetric addition of trimethylsilyl cyanide to aldehydes has been investigated. The complexes are catalytically active at substrate-to-catalyst ratios as high as 1000:1, and the optimal catalyst (2e) which is derived from (R,R)-1,2-diaminocyclohexane and 3,5-di-tert-butyl-2-hydroxybenzaldehyde produces trimethylsilyl ethers of cyanohydrins with up to 90% enantiomeric excess at ambient temperature. Water plays a key role in these reactions since under strictly anhydrous conditions much lower enantiomeric excesses are produced. The role of water has been shown to be to generate dimeric complexes of the form [(salen)Ti(μ-O)]2 (4) which are the real catalyst precursors. A structure for one of these complexes (4a derived from (R,R)-1,2-diaminocyclohexane and 2-hydroxybenzaldehyde) has been determined by X-ray crystallography. The dimeric complexes are more active than the dichloride precursors, and at substrate-to-catalyst ratios between 100 and 1000:1 give cyanohydrin trimethylsilyl ethers with up to 92% enantiomeric excess in less than 1 h at ambient temperature.

Dedicated to Professor Dieter Seebach on the occasion of his 65th birthdayThe utility of the chiral [Ti(m-O)(salen)] 2 complexes (R)-and (S)-1 (H 2 salen was prepared from (R,R)-or (S,S)-cyclohexane-1,2-diamine and 3,5-di(tert-butyl)-2-hydroxybenzaldehyde) as catalysts for the asymmetric addition of KCN and Ac 2 O to aldehydes to produce O-acetylcyanohydrins was investigated. It was shown that the complexes were active at a substrate/catalyst ratio of 100 : 1 and produced the O-protected cyanohydrins with ee in the range of 60 ± 92% at À 408. Other complexes, [Ti 2 (AcO) 2 (m-O)(salen) 2 ] ((R)-4) and [Ti(CF 3 COO) 2 (salen)] ((R)-5), were prepared from (R)-1 by treatment with different amounts of Ac 2 O and (CF 3 CO) 2 O, and their catalytic activities were tested under the same conditions. The efficiency of (R)-4 was found to be even greater than that of (R)-1, whereas (R)-5 was inactive. The synthesis of the corresponding salen complexes of V IV and V V ,, was elaborated, and their X-ray crystal structures were determined. The efficiency of (R)-3 was sufficient to produce O-acetyl derivatives of aromatic cyanohydrins with ee in the range of 80 ± 91% at À 408.Introduction. ± As enantiomerically pure cyanohydrins are versatile intermediates in organic synthesis, many synthetic approaches to their syntheses are being vigorously pursued [1]. The catalytic ways of making this class of compounds rely upon the asymmetric addition of a cyanide source to the carbonyl group of aldehydes, as catalyzed by enzymes [2] or purely chemical chiral catalysts [3]. Enantiomerically enriched O-protected cyanohydrins are customarily made by the reaction of aldehydes with Me 3 SiCN usually catalyzed by chiral Lewis acids [1]. We recently reported an efficient catalysis of this reaction by the chiral binuclear [Ti IV (salen)] complex 1 (Fig. 1), active at a ratio of substrate/catalyst as high as 1000 : 1 and promoting the addition at room temperature with ee in the range of 80 ± 92% [4]. Very efficient catalysts based on bifunctional complexes of Al III and Ti IV have also been developed by Shibasaki and co-workers, giving O-(trimethylsilyl) derivatives of cyanohydrins with ee as high as 90 ± 99% at À 428 [5].Unfortunately, Me 3 SiCN is an expensive material, and HCN is extremely toxic. Evidently, there is a need to find cheaper and safer initial materials for the synthesis of enantiomerically pure O-protected cyanohydrins. This paper reports the asymmetric synthesis of O-acetylcyanohydrins by the reaction of KCN, acetic anhydride (Ac 2 O),

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nitriles nitriles (benzene compounds) Q 0520 -125Asymmetric Trimethylsilylcyanation of Benzaldehyde Catalyzed by (Salen)Ti(IV) Complexes Derived from (R)-and/or (S)-4-Hydroxy-5-formyl[2.2]paracyclophane and Diamines.-A method for the catalytic, asymmetric preparation of cyanohydrins, versatile intermediates in organic synthesis, is presented using enantiomerically pure, cyclophane-based (salen)Ti(IV) complexes as catalysts. -(BELOKON, Y.; MOSCALENKO, M.; IKONNIKOV, N.; YASHKINA, L.; ANTONOV, D.; VORONTSOV, E.; ROZENBERG, V.; Tetrahedron

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A (salen)titanium catalyst has been found to induce the asymmetric addition of potassium cyanide and acetic anhydride to aldehydes, giving enantiomerically enriched cyanohydrin esters with up to 92% enantiomeric excess using just 1 mol% of the catalyst. This is the first report of the asymmetric synthesis of cyanohydrin derivatives using a cyanide source which is non-volatile and inexpensive.

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Chiral copper(II) and cobalt(III) complexes (1−5 and 6, respectively) derived from Schiff bases of (S)-2-(aminomethyl)pyrrolidine and salicylaldehyde derivatives were employed in a mechanistic study of the Henry reaction-type condensation of nitromethane and o-nitrobenzaldehyde in CH 2 Cl 2 (CD 2 Cl 2 ), containing different amounts of water. The reaction kinetics was monitored by 1 H and 13 C NMR. The addition of water had a different influence on the activity of the two types of complexes, ranging from a crucial positive effect in the case of the copper(II) complex 2 to insignificant in the case of the stereochemically inert cobalt(III) complex 6. No experimental support was found by 1 H NMR studies for the classical Lewis acid complexation of the carbonyl group of the aldehyde by the central copper(II) ion, and, moreover, density functional theory (DFT) calculations support the absence of such coordination. On the other hand, a very significant complexation was found for water, and it was supported by DFT calculations. In fact, we suggest that it is the Brønsted acidity of the water molecule coordinated to the metal ion that triggers the aldehyde activation. The rate-limiting step of the reaction was the removal of an α-proton from the nitromethane molecule, as supported by the observed kinetic isotope effect equaling 6.3 in the case of the copper complex 2. It was found by high-resolution mass spectrometry with electrospray ionization that the copper(II) complex 2 existed in CH 2 Cl 2 in a dimeric form. The reaction had a second-order dependence on the catalyst concentration, which implicated two dimeric forms of the copper(II) complex 2 in the rate-limiting step. Furthermore, DFT calculations help to generate a plausible structure of the stereodetermining transition step of the condensation.