O-TMS cyanohydrins

A highly anti-selective hydrocyanation of (7 )-jV-Boc-2, 2-dimethylthia-zolidine-4-carbaldehyde (Gamer s aldehyde) with hydrogen cyanide in the presence of a Lewis acid has been reported [78]. In the initial study, we applied the procedure to the synthesis of anti-O-TMS cyanohydrin 23. However, the cyanosilylation of 22 in the presence of Lewis acid such as zinc iodide (Znl2), zinc bromide (ZnBr2) or boron trifluoride (BFy) diethyl ethcrate was problematic, leading only to traces of 23. 

Alkylation reactions of (207) are not so promising. In general, a-hydroxyamides are best prepared from carbonyls by cyanohydrin formation and subsequent hydrolysis of the nitrile function. However, this approach is usually not feasible with aryl ketones as the equilibrium between ketone and cyanohydrin lies far to the left. This problem can be overcome by using trimethylsilyl cyanide acid hydrolysis of the resulting O-TMS cyanohydrin gives a-hydroxyamides in >70% yield. Some ketones however, still cannot be satisfactorily transformed by this method. Treatment of bis-NO-trimethylsilylacetamide or iV-trimethylsilyl-acetamide with n-BuLi results in the formation of anions (209) and (210), respectively, which condense with carbonyls to give /8-hydroxyamides or their iV-methyl derivatives in fair to excellent yields. " ... 

Oxidation of a cyanohydrin derived from a conjugated aldehyde (as the O-TMS derivative) using py-ridinium dichromate (PDC) in DMF gave an a,p-unsaturated lactone (6 -butenolide) as the major product (equation 12). Simple nonconjugated cyanohydrins are not satisfactory substrates for the synthesis of acyl cyanides using PDC, because they seem to add to the initially formed acyl cyanides, leading ultimately to cyanohydrin esters. Oxidation of cyanohydrin to acyl cyanides can be carried out either by means of manganese dioxide, mthenium-catalyzed oxidation with r-butyl hydroperoxide or NBS. ... 

The first total synthesis of amiclenomycin, an inhibitor of biotin biosynthesis, was completed by A. Marquet and co-workers. In order to prove its structure unambiguously, both the cis and trans isomers were prepared. The L-amino acid functionality was installed by a Strecker reaction using TMSCN in the presence of catalytic amounts of Znla. The resulting O-TMS protected cyanohydrin was exposed to saturated methanolic ammonia solution, which gave rise to the corresponding a-amino nitrile. Enzymatic hydrolysis with immobilized pronase afforded the desired L-amino acid. 

Our first approach to 1 is based on a retrosynthetic analysis depicted in Fig (8). The crucial step to construct the cw-fused bicyclic ring skeleton of 1 is the intramolecular allylic amination of a cw-allylic carbonate 25. The paUadium-catalyzed allylation takes place with retention of the configuration [76] and requires the c/s-isomer 25 for the ring closure. Compound 25 may be derived from keto acid 24 through a sequence of reactions including esterification, O-methoxycarbonylation, removal of the Boc and benzylidene groups, dehydrative cyclization, reductive alkylation and ureido formation. The last five transformations are to be conducted in a successive manner, i.e., without isolation of the intermediates. The 4-carboxybutyl chain of 1 may be installed by the reaction of O-trimethylsilyl (TMS) cyanohydrin 23 with a di-Grignard... 

Subsequently, the Feng group developed an enantioselective cyanosilylation of ketones by a catalytic double-activation catalyst system composed of chiral (J ,J )-salen 16-triethylaluminium complex and N-oxide 17 (Scheme 19.10). High catalytic turnovers (200 for aromatic ketones, 1000 for aliphatic ones) with high enantioselectivity (up to 94% enantiomeric excess for aromatic ketones, up to 90% enantiomeric excess for aliphatic ones) were achieved under mild reaction conditions. Based on the control experiments, a double-activation model was suggested (Scheme 19.10). The chiral aluminium complex performed as a Lewis acid to activate the ketone, whereas the N-oxide acted as a Lewis base to activate trimethylsilyl cyanide and form an isocyanide species. The activated nucleophile and ketone attracted and approached each other, and so the transition state was formed. The intramolecular transfer of cyanide to the carbonyl group gives the product cyanohydrin O-TMS ether. 

In the presence of a Lewis acid such as SnCh, BF3 OEt2, ot TiC104, TMS-CN reacts with acetals to give cyanohydrin ethers. o-Ribofuranosyl cyanide, an important intermediate of C-nucleoside synthesis, is prepared from a furanosyl acetate (Scheme 23). ... 

In catalytic processes with enzymes such as o-oxynitrilase and (K)-oxynitrilase (mandelonitrilase) or synthetic peptides such as cyclo[(5)-phenylalanyl-(5)-histidyl], or in reaction widi IMS-CN promoted by chiral titanium(IV) reagents or with lanthanide trichlorides, hydrogen cyanide adds to numerous aldehydes to form optically active cyanohydrins. The optically active Lewis acids (8) can also be used as a catalyst. Cyanation of chiral cyclic acetals with TMS-CN in the presence of titanium(IV) chloride gives cyanohydrin ethers, which on hydrolysis lead to optically active cyanohydrins. An optically active cyanohyrMn can also be prepared from racemic RR C(OH)CN by complexation with... 

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