DIETHYLALUMINUM CYANIDE

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... 

Cyanide addition has also been done under Lewis acid catalysis. Triethylaluminum-hydrogen cyanide and diethylaluminum cyanide are useful reagents for conjugate... 

Diethylaluminum cyanide mediates conjugate addition of cyanide to a, (3-unsaturated oxazolines. With a chiral oxazoline, 30-50% diastereomeric excess can be achieved. Hydrolysis gives partially resolved a-substituted succinic acids. The rather low enantioselectivity presumably reflects the small size of the cyanide ion. 

Diethylaluminum cyanide can also be used for preparation of (3-hydroxynitriles. 

PREPARATION OF CYANO COMPOUNDS USING ALKYLALUMINUM INTERMEDIATES. I. DIETHYLALUMINUM CYANIDE, 52, 90 PREPARATION OF a,g-UNSATURATED ALDEHYDES via THE WITTIG REACTION CYCLOHEXYLIDENE-... 

After this period, the dropping funnel and the vacuum takeoff are replaced by the short-path distillation assembly shown in Figure 2. The system is protected by a Drierite tube and the benzene is distilled under reduced pressure (water aspirator). After the benzene is removed, the benzene-containing receiver is replaced with a clean, dry flask, and the system is connected to an eflScient vacuum pump. The pressure in the system is reduced to 0.02 mm., and the flask is immersed deeply in an oil bath (Figure 2) heated to about 200°. After about 1 ml. of fluid forerun is collected, the diethylaluminum cyanide distils at 162° (0.02 mm.) (Note 7) and is collected in a tared 200-ml. receiver by heating the side arm and the adaptor with a stream of hot air or an infrared lamp (Note 8). After all the distillate is collected in the receiver (Note 9), dry nitrogen is admitted to the evacuated apparatus and the receiver is stoppered and weighed. Diethylaluminum cyanide is obtained usually as a pale yellow syrup (Note 10) in 60-80% yield (26.7-35.6 g.) (Note 11). 

The stopper of the flask is quickly replaced by the nitrogen adaptor, and after placing the system under a nitrogen atmosphere, the diethylaluminum cyanide is treated with 130 ml. 

The reaction mixture containing about 13%. 2M) of diethylaluminum cyanide and a small amount of ethylaluminum dicyanide may be used for most hydrocyanation processes without further purification. Care must be taken to have no unchanged triethylaluminum, since the submitters have observed that hydrocyanation of A -ll-keto steroids with diethylaluminum cyanide is greatly retarded by the presence of a small amount of unchanged triethylaluminum. ... 

It takes considerable time (5-10 hours) to dissolve the diethylaluminum cyanide. Magnetic stirring is not effective unless most of the material goes into solution. 

Crystals of 6-methoxy-l-tetralone may separate from the solution on cooling, but redissolve upon addition of the cooled diethylaluminum cyanide solution. 

For preparation of diethylaluminum cyanide, see the preceding procedure. Both the submitters and checkers employed a crude reagent solution rather than a solution prepared from distilled diethylaluminum cyanide. 

Formation of diethylaluminum cyanide from triethyl-aluminum and hydrogen cyanide was noted initially by the submitters and later by Stearns, but isolation and characterization of the product were first performed by the submitters. An unpractical process comprising heating diethylaluminum chloride and sodium cyanide in benzene for 21 days has been reported. ... 

Diethylaluminum cyanide is a useful, potent reagent for hydrocyanation of various compounds. Features of this reagent as compared with the triethylaluminum-hydrogen cyanide reagent may be seen from the literature. - ... 

Except for the well-documented conjugate additions of diethylaluminum cyanide,92 triethylaluminum-hydrogen cyanide and Lewis acid-tertiary alkyl isonitriles,93 examples of Lewis acid catalyzed conjugate additions of acyl anion equivalents are scant Notable examples are additions of copper aldimines (233),94, 94b prepared from (232), and silyl ketene acetals (234)940 to a,(3-enones which afford 1,4-ketoal-dehydes (235) and 2,5-diketo esters (236), respectively (Scheme 37). The acetal (234) is considered a glyoxylate ester anion equivalent. 

---