Aldehydes with cyanotrimethylsilane

Table 8. Asymmetric Hydrocyanation of Aldehydes with Cyanotrimethylsilane...

Asymmetric hydrocyanation of aldehydes.3 This reaction can be effected by reaction of aliphatic or aromatic aldehydes with cyanotrimethylsilane and an optically active reagent (1) derived from (2R,3R)-tartaric acid, and dichlorodiisopro-poxytitanium(IV). The actual chiral reagent may be 2, shown by H NMR to be... 

The addition of HCN to aldehydes or ketones produces cyanohydrins. This is an equilibrium reaction. For aldehydes and aliphatic ketones the equilibrium lies to the right therefore the reaction is quite feasible, except with sterically hindered ketones such as diisopropyl ketone. However, ketones ArCOR give poor yields, and the reaction cannot be carried out with ArCOAr since the equilibrium lies too far to the left. With aromatic aldehydes the benzoin condensation (16-54) competes. With oc,p-unsaturated aldehydes and ketones, 1,4 addition competes (15-33). Ketones of low reactivity, such as ArCOR, can be converted to cyanohydrins by treatment with diethylaluminum cyanide (Et2AlCN see OS VI, 307) or, indirectly, with cyanotrimethylsilane (MesSiCN) in the presence of a Lewis acid or base, followed by hydrolysis of the resulting O-trimethylsilyl cyanohydrin (52). The use of chiral additives in this latter reaction leads to cyanohydrins with good asymmetric... 

Aldehydes, ketones, and acetals react with allyltrimethylsilane in the presence of a catalytic amount of BiX3 (X = C1, Br, OTf) to give homoallyl alcohols or homoallyl alkyl ethers (Equation (52)).91-93 The BiX3-catalyzed allylation of aldehydes and sequential intramolecular etherification of the resulting homoallylic silyl ethers are involved in the stereoselective synthesis of polysubstituted tetrahydropyrans (Equation (53)).94,95 Similarly, these Lewis acids catalyze the cyanation of aldehydes and ketones with cyanotrimethylsilane. When a chiral bismuth(m) catalyst is used in the cyanation, cyanohydrines are obtained in up to 72% ee (Equation (54)). a-Aminonitriles are prepared directly from aldehydes, amines, and cyanotrimethysilane by the BiCl3-catalyzed Strecker-type reaction. 

The first study of catalysis by a nanoporous coordination polymer used a simple lamellar coordination polymer of Cd and 4,4 -bipyridine in which several aldehydes were tested for cyanosilation with cyanotrimethylsilane.86 Good yields were found for smaller molecules, with progressively poorer yields for larger ones, while control experiments using Cd(N03)2 and 4,4 -bipyridine as catalysts resulted in no reaction, confirming the role of the coordination polymer s porosity in catalyzing the reaction. 

Alkyl aryl ketones. The adducts (2) of aromatic aldehydes and cyanotrimethylsilane can be deprotonated with LDA (THF or ether, - 78°). The resulting anions can be alkylated by alkyl iodides, bromides, and tosylates in good yield. The products are usually not isolated but are hydrolyzed by dilute hydrochloric acid or benzyltrimethylammonium fluoride to ketones in yields mainly of 80-90%. 

Aldehydes and ketones are readily transformed into the corresponding cyanohydrin trimethylsilyl ethers when treated with cyanotrimethylsilane in the presence of Lewis acids (eq 1), triethylamine, or solid bases such as Cap2 or hydroxyapatite. The products can be readily hydrolyzed to the corresponding cyanohydrins. The cyanosilylation of aromatic aldehydes can be achieved with high enantioselectivity in the presence of catalytic amounts of a modified Sharpless catalyst consisting of titanium tetraisopropoxide and L-(+)-diisopropyl tartrate (eq 2). Catalysis with chiral titanium reagents yields aliphatic and aromatic cyanohydrins in high chemical and optical yields... 

Addition to Carbonyls, Imines (Strecker-type Reactions), and Heteroaromatic Rings (Reissert-type Reactions). Cyanohydrin trimethylsilyl ethers are of significant synthetic interest as they can be transformed into a variety of multifunctional intermediates. Aldehydes and ketones can be enantioselectively converted to cyanohydrin trimethylsilyl ethers when treated with cyanotrimethylsilane in the presence of a Lewis acid and a chiral ligand. Enantioselective and/or diastereoselective formation of cyanohydrins and their derivatives has been reported and most of these reactions involve chiral ligands and metal catalysts containing Ti (eq 24), Sm (eq 25), and A1 (eq 26). ... 

In the case of TMEDA, stereoselection in favor of the syn product (98 2) is enhanced over that achieved with Diiso-propylethylamine (94 6). Along with bases sueh as Triethy-lamine and ethylisopropylamine, TMEDA facilitates the preparation of cyanohydrin trimethylsilyl ethers from aldehydes and Cyanotrimethylsilane. It has been suggested that eoordination by nitrogen induces formation of an active hypervalent cyana-tion intermediate from cyanotrimethylsilane. The conjugate addition of thiols to enones has been successfully catalyzed by using TMEDA in methanol at room temperature, as exemplified by the reaction of 10-mercaptoisobomeol and 4-/-butoxycyclopentenone... 

Acyloins.1 Acyloins, both aliphatic and aromatic, can be prepared in good yield by reaction of Grignard reagents with O-trimethylsilyl cyanohydrins, which are readily available by reaction of cyanotrimethylsilane with aldehydes and ketones (4, 542-543). 

Acyloins. The anion of the adduct of cyanotrimethylsilane with benzaldehyde reacts with aldehydes and ketones to form acyloin silyl ethers (2), by way of a 1,4-O-siIyI rearrangement, a—>b. On hydrolysis acyloins (3) are obtained in high yield. 

Cyanosilylation. The chiral titanium reagent, prepared from the lithium salt of BINOL with TiCL, has been used as a catalyst for the asymmetric addition of cyanotrimethylsilane to aldehydes. In the example shown, the cyanohydrin is obtained with <82% ee (eq 9). 

Cyanosilylation. Another preparative procedure of BINOL-TiCl2 and the use thereof was reported in the asymmetric catalysis of the addition reaction of cyanotrimethylsilane to aldehydes. The dilithium salt of BINOL in ether was treated with... 

Enantioselective Cyanohydrin Formation. Magnesium complexes formed with the anionic semicorrin-type ligand (5) catalyze the addition of Cyanotrimethylsilane to aldehydes, leading to optically active trimethylsilyl-protected cyanohydrins. In the presence of 20 mol % of the chloromagnesium complex (9), prepared from equimolar amounts of (5) and BuMgCl, cyclohexanecarbaldehyde is smoothly converted to the corresponding cyanohydrin derivative with 65% ee. Addition of 12 mol % of the bisoxazoline (10) results in a dramatic increase of enantioselectivity to 94% ee (eq 8). Replacement of (10) by its enantiomer reduces the selectivity to 38% ee. This remarkable... 

In the addition reaction of cyanotrimethylsilane [147] to aliphatic aldehydes, another synthetic application of a BINOL-Ti catalyst was reported by Reetz [88]. In this instance, however, BINOL-TiCh was prepared by treatment of the lithium salt of BINOL with TiCU in ether (vide supra). The BINOL-TiCh thus obtained was used as a catalyst for the cyanosilylation reaction to give the cyanohydrins in up to 82 % ee (Sch. 62). 

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