Reductions iminium ions, lithium aluminum hydride

The reduction of the double bond of an enamine is normally carried out either by catalytic hydrogenation (MS) or by reduction with formic acid (see Section V.H) or sodium borohydride 146,147), both of which involve initial protonation to form the iminium ion followed by hydride addition. Lithium aluminum hydride reduces iminium salts (see Chapter 5), but it does not react with free enamines except when unusual enamines are involved 148). 

Reductions of Imines and Derivatives. Preformed imines (eq 7), iminium ions (eq 8), oximes (eq 9), oxime derivatives (eqs 10 and 11), hydrazones (eq 12), and other iV-heterosubstituted imines (eqs 13 and 14) are reduced to the corresponding amine derivatives by NaBHsCN, usually in acidic media (see also Lithium Aluminum Hydride and Sodium Boro-hydride). 

Mechanism 21.1 shows the reduction of amides with lithium aluminum hydride. The reduction of amides follows a similar course to the reduction of esters (Section 19.13). A tetrahedral intermediate is formed by the addition of hydride (step 1), and undergoes elimination (step 2). In the case of an ester, the alkoxy group is lost to give an intermediate aldehyde. Amides, on the other hand, retain the nitrogen and lose the oxygen from the tetrahedral intermediate. The iminium ion formed undergoes addition of a second hydride and is reduced to the amine in step 3. 

Lhommet s team has reported a second synthesis of (—)-lupinine (926) based on a convenient multicomponent condensation of the 5-ketoester 1024, (S)-phenylglycinol (1025) and acrolein (Scheme 127). That the reaction yielded a 2 1 mixture of chiral tetrahydro[l,3]oxazolo[3,2-mixture—effectively a masked iminium ion—with sodium triacetoxyborohydride led to the piperidine (—)-1027 as a single isomer. Hydrogenolysis of 1027 followed by treatment with p-toluenesulfonic acid brought about cyclization to the bicycHc lactam (- -)-1028, which underwent reduction of both the ester and the lactam with lithium aluminum hydride to complete this short synthesis of (—)-926. 

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