Stereoselective reactions metal-ammonia reduction

Stilbene derivatives can be reduced with alkali metals in liquid ammonia. The reaction is usually performed in a homogeneous medium to give substituted diphenylethane compounds as a mixture of enantiomeric forms. However, there are compounds (particularly, biologically active ones) for which the stereospecificity of synthesis has decisive importance. A simple modification of the reduction method with an alkali metal in liquid ammonia was found (Collins and Hobbs 1983), which makes it possible to perform the process stereoselectively. The metal is not predissolved, as is usual, but is added in small portions without trying to make the reaction medium homogeneous. Stereoselectivity is ensured by carrying out the reduction on the surface of the metal and not in the solution bulk. 

Selective catalytic hydrogenation of the 6,7-double bond of 17/3-acetoxy-7-methylandrosta-4,6-dien-3-one was achieved with Pd-C-PhCH20H and gave the 7/8-methyl dihydro-compound. Added FeCls has been reported to improve the selectivity of reduction of a,/S-enones in metal-ammonia reactions, thereby improving the yield of the saturated ketones. Similar improvements were observed in the lithium-ethylamine reductions at -78 C when a substantial excess of lithium was used and t-butyl alcohol was the proton source. The influence of solvent and added nitrogenous bases on the stereoselectivity of hydrogenation of A - and A -3-oxo-steroids with Pd catalysts has been studied, and the stereoselectivity of Pd-catalysed hydrogenation of various A -7-oxo-steroids has been reported to be unaffected by substituents at C-3 or C-17. 

The Birch reductions of C C double bonds with alkali metals in liquid ammonia or amines obey other rules than do the catalytic hydrogenations (D. Caine, 1976). In these reactions regio- and stereoselectivities are mainly determined by the stabilities of the intermediate carbanions. If one reduces, for example, the a, -unsaturated decalone below with lithium, a dianion is formed, whereof three different conformations (A), (B), and (C) are conceivable. Conformation (A) is the most stable, because repulsion disfavors the cis-decalin system (B) and in (C) the conjugation of the dianion is interrupted. Thus, protonation yields the trans-decalone system (G. Stork, 1964B). 

The Birch reduction has been applied to electron-deficient pyrroles substituted with a chiral auxiliary at the C(2)-position <1999TL435>. Using either (—)-8-phenylmenthol or (- -)-/ra /-2-(ot-cumyl)cyclohexanol as auxiliaries, high levels of stereoselectivity were obtained. Pyrrole 911, prepared from the l/7-pyrrole-2-carboxylic acid 910 in 90% yield, was reduced under modified Birch conditions (Scheme 176). The best conditions involved lithium metal (3 equiv), liquid ammonia and THE at —78°C. The addition of A, A -bis(2-methoxyethyl)amine (10 equiv) helped to reduce side reactions caused by the lithium amide formed in the reaction <1998TL3075>. After 15 min, the Birch reductions were quenched with a range of electrophiles and in each case 3,4-dehydroproline derivatives 912 were formed in excellent yields and with good diastereoselectivities. 

Alkali metal reduction is performed with Li, Na, and occasionally Ca in liquid ammonia, ethylamine, or especially diethylamine. The regio- and stereoselectivity of the reaction is satisfactory. Two such reactions are presented in Eqs. 171 and... 

Alkynes can also be reduced to alkenes by using either sodium or lithium metal in liquid ammonia or in low-molecular-weight primary or secondary amines. The alkali metal is the reducing agent and, in the process, is oxidized to M, which dissolves as a metal salt in the solvent for the reaction. Reduction of an alkyne to an alkene by lithium or sodium in liquid ammonia, NH3(Z), is stereoselective it involves mainly anti addition of two hydrogen atoms to the triple bond. 

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