Ketones, reaction with imine carbanions

In the presence of excess monoalkylamine, carbonyl compounds in aqueous solution are in equilibrium with the corresponding imine. In most cases these imines cannot be isolated but they are reduced at a less negative potential than the carbonyl compound. Selective reduction of such equilibrium mixtures is a useful route to alkylamines from ketones in yields of 70-90%. The process fails with hindered ketones such as camphor and with bulky amines such as fert.-butyl amine. Overall the reaction has advantages of lower costs and simpler work-up compared to the use of cyanoborohydride reducing agents. In the electrochemical reaction, protonation of carbanion intermediates occurs from the more hindered side and where two isomeric products are fomied, the least hindered amine predominates [193]. 

This chapter focuses the attention on the reactions of nonstabilized carbanionic compounds such as alkyl, vinyl, aryl, alkynyl metals, etc., and the chemistry of the stabilized system, i.e. allylic, propargylic or oxaallylic carbanions is presented in Volume 2 of this series. Electrophiles with C=X bonite which are discussed include aldehydes, ketones, epoxides, aziridines, acetals, orthoesters and imines, all of which turn into highly reactive electrophiles in the presence of Lewis acids. 

Reactions with Active Methylene Compounds. Enolates of ketones," esters," enediolates," 1,3-dicarbonyl compounds," amides and lactams," as well as nitrile-stabilized carbanions," can be alkylated with benzyl bromide. Cyclohexanone may be benzylated in 92% ee using a chiral amide base." Amide bases as well as alkoxides have been employed in the case of nitrile alkylations." Benzylation of metalloenamines may be achieved and enantioselective reactions are possible using a chiral imine (eq 3). However, reactions between benzyl bromide and enamines proceed in low yield. The benzylation of a ketone via its enol silyl ether, promoted by fluoride, has been observed. ... 

In Section 9.4.A, it was noted that there were problems with aldol-type reactions, especially with the directed aldol condensation. In particular, aldehydes with an a-hydrogen have great difficulty adding to ketones due to their propensity for self-condensation. The ability to use kinetic control conditions in enolate reactions of ketones and aldehydes often solves this problem. There are also several alternative approaches that involve the use of carbanions derived from imines and hydrazones and these can be very useful. l... 

Isomerizations of Unsaturated Compounds. r-BuOK is an effective base for bringing about migrations of double bonds in alkenes and alkynes via carbanion intermediates, but since the base promotes these reactions most effectively in DMSO, they will be described in more detail under Potassium tert-Butoxide-Dimethyl Sulfoxide. Important exanples of enone deconjugations with i-BuOK/f-BuOH which proceed via di- and trieno-late intermediates are shown in eqs 30 and 31. Potassium i-pentoxide is effective in promoting the latter reaction, but various lithium amide bases are not, apparently because they de-protonate the enone at the a -position regioselectively. The isomerization of Q ,/8-unsaturated imines to alkenyl imines (eq 32) is an important step in an alternative method for reduction-alkylation of a ,/8-unsaturated ketones. ... 

The modification of the Peterson reaction using an N-trimethylsilylamide anion instead of an a-silyl carbanion offers a promising route to the corresponding imines. Treatment of N-(p-tolyl)-N-trimethylsilylamide anion with carbonyl compounds yields the corresponding ketimines [400]. In particular, LiHMDS has been utilized for the preparation of N-trimethylsilylimines, which are useful as masked imine derivatives in the synthesis of yS-lactam antibiotics [401-407]. Reactions of LiHMDS with non-enolizable aldehydes, enolizable aldehydes, ketones, a diketone, and a-keto esters give the respective imines (Scheme 2.153) [408-413]. Chloro-trimethylsilane is added to convert the generated lithium trimethylsilanolate into hexamethyldisiloxane. 

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