Cyanoformate esters

Glycine Ethyl Ester Hydrochloride (14, 46) Cyanoformic esters are reduced with a metal, such as zinc, iron, or aluminum, in the presence of an organic acid. Ger. pat. 594,219 [C. A. 28, 3417 (1934)]. Cyanoformic ester is reduced in alcohol in the presence of concentrated hydrochloric acid, with a platinum catalyst and hydrogen at 40 atna. pressure. Ger. pat. 597,305 [C. A. 28, 5078 (1934)]. 

The chemistry of cyanoformate esters has been the subject of a recent review (Ref. 46). 

Cyanoformate esters may be prepared through reaction of alkyl chloroformates with cyanides salts by procedures using phase-transfer catalysis with 18quaternary ammonium salts (Ref. 44) according to scheme 46. 

Scheme 46 Preparation of cyanoformate esters from chloroformates.

Although convenient for the preparation of small quantities of cyanoformate esters such as ethyl cyanoformate, we found the method to be unsatisfactory for the production on a larger scale because of the formation of carbonate esters reducing the yield. 

Optically pure cyanohydrins serve as highly versatile synthetic building blocks [24], Much effort has, therefore, been devoted to the development of efficient catalytic systems for the enantioselective cyanation of aldehydes and ketones using HCN or trimethylsilyl cyanide (TMSCN) as a cyanide source [24], More recently, cyanoformic esters (ROC(O)CN), acetyl cyanide (CH3C(0)CN), and diethyl cyanophosphonate have also been successfully employed as cyanide sources to afford the corresponding functionalized cyanohydrins. It should be noted here that, as mentioned in Chapter 1, the cinchona alkaloid catalyzed asymmetric hydrocyanation of aldehydes discovered... 

Scheme 4.10 Enantioselective cyanation of aldehydes with cyanoformic esters catalyzed by (S)-ALB (7) and cinchonine.

A synthesis of aroylformic esters is based on the addition of ArB(OH)2 to cyanoformic esters, with H3BO3 acting as an additive for the reaction. Addition reations are followed by cyclization as situation prevails, as in the case of the addition of boronic acids to... 

Addition and cycloaddition. Two slightly different protocols are available for achieving addition of 1-alkynes to trifluoromethyl ketones use either CuOTf and t-BuOK with Xantphos in THF at 60°, or Cu(OTf)2 and two equivalents of t-BuOK and 1,10-phenanthro-line in toluene at 100°. Cyanoformate esters can contribute the CN group as an addend to react with organoazides in a [3+2]cycloaddition catalyzed by CuOTf. ... 

By using cyanoformate esters as electrophiles, Johnson and coworkers were able to employ catalytic amounts of the cyanide initiator in reactions with acyl silanes. This process led to carbon-carbon bond formation via C-acylation. For example, acyl silane 61 and ethylcyanoformate combined under these conditions to provide the tertiary alcohol silyl ether 62 in nearly quantitative yield. Johnson s group has also developed an asymmetric version of this process, utilizing the Jacobsen (salen)aluminum system as a chiral carrier for the cyanide anion. ... 

Due to the high price of trimethylsilyl cyanide, access to alternative cyanation reagents is desirable. In this regard, cyanoformate esters (CNCO2R) have been employed, providing direct access to O-alkojycarbonyl-functionalised cyanohydrins, which are stable and not easily hydrolysed by moisture in air. Moreover, they are useful synthetic intermediates and can be applied in the synthesis of a-amino alcohols and (3-substituted unsaturated nitriles from O-carbonylated allylic cyanohydrins. ... 

Form Supplied in colorless liquid methyl cyanoformate, as well as the ethyl and benzyl analogs, is available commercially. Preparative Methods small quantities of cyanoformate esters (up to 30 g) may be conveniently prepared from alkyl chlorofor-mates by procedures employing phase-transfer catalysis with either 18-Crown- or Tetra-n-butylammonium Bromide but several workers have found the products to be unsatisfactory when prepared on a larger scale. 

---