Metal catalyzed, cyanation acids

The Strecker reaction [1] starting from an aldehyde, ammonia, and a cyanide source is an efficient method for the preparation of a-amino acids. A popular version for asymmetric purposes is based on the use of preformed imines 1 and a subsequent nucleophilic addition of HCN or TMSCN in the presence of a chiral catalyst [2], Besides asymmetric cyanations catalyzed by metal-complexes [3], several methods based on the use of organocatalysts have been developed [4-14]. The general organocatalytic asymmetric hydrocyanation reaction for the synthesis of a-amino nitriles 2 is shown in Scheme 5.1. 

Coordinated cyanamide does not add OH" to form the N-bound urea complex since it de-protonates 5.2) to ve the unreactive [Co(NCNH)(NH3)5p ion, but in acid it readily loses NH to form N-coordinated cyanate (equation 27). The analogous dimethylcyanamide complex cannot deprotonate and adds OH" to form urea (Scheme 21), but this does not proceed further to coordinated carbamic add and NHMCj in a process analogous to that suggested for the function of Ni in the metalloenzyme jack bean urease (which catalyzes the convemioo of urea to these products), nor does it lose NHMc2 to form the cyanato complex as suggested by Balahura and Jordan for the similar urea derivatives (equation 28). Alternatively, in acid solution the protonated urea rapidly isomerizes to the O-coordinated complex (r,/2 a 40 s, 25 °C Scheme 21). This isomer undergoes OH -catalyzed hydrolysis at the metal rather than at acyl carbon, so the function of the metalloenzyme has not been duplicated in this system. A similar property is found for 0-bound urea (equation 29). ... 

Cyanate/Cyanurate. When aryl cyanate esters are heated to 150 to 250°C, they cyclotrimerize to cyanuric acid esters (Fig. 3.62). They can be catalyzed by organo-metallic and active hydrogen compounds. When the monomer is a dicyanate such as bisphenol A dicyanate (Fig. 3.63), the result is a highly cross-linked heterocyclic polymer (Table 3.57). Using a novolac polycyanate has produced Tg and useful life over 300°C. 

Optically active cyanohydrins can be easily transformed to P-hydroxy amines, a-hydroxy and a-amino carboxylic acids, which represent versatile intermediates for the synthesis of biologically important compounds, including insecticides and medicines [189, 190]. Asymmetric cyanation of carbonyl compounds catalyzed by chiral metal complexes, particularly titanium compounds, has provided one of the most convenient protocols to the access of these type of compounds. The first example of catalytic asymmetric cyanation of aliphatic aldehydes was realized in Reetz s group using BINOL-Ti complex as the catalyst to give the cyanohydrins in up to 82% ee [104] (Scheme 14.85). 

The Strecker reaction is an efQdent method for the preparation of a-amino acids which was first reported by Adolf Strecker over 100 years ago [120]. Now, several methods for asymmetric cyanations catalyzed by metal-complexes or organocata-lysts have been developed [121-124],... 

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