Organolithium compounds regioselectivity

Unsymmetrical dienynes react regioselectively with organolithium compounds at the less substituted double bond (Scheme 2.37). Thus, addition of n-butyllithium to 2-methylhexa-l,5-dien-3-yne (107) led after hydrolysis to vinylallene 108, whereas the corresponding carbolithiation of the linear isomer 109 furnished product 110 with 55% yield [68]. 

Coldham and coworkers have shown that the asymmetric deprotonation protocol can be used to regioselectively alkylate the 5-position of imidazolidines (Scheme 35). The process is used as part of a sequence that results in asymmetric alkylation of 1,2-diamines with high stereoselectivity. The yields are limited, in this case, by the barrier to rotation around the carbamate C—N bond. Thus, only the amide rotamer having the carbonyl group syn to C-5 of the heterocycle is deprotonated. There are several examples in this review where this limitation is possible whether it is a factor or not may depend on the temperature at which amide bond rotation occurs versus the stability of the organolithium compound. In this case, the barrier to amide bond rotation was determined as 16.6 kcalmoD at 60 °C. 

Regioselective generation of the organolithium compound benefits from two stabilizing effects. 

The regioselectivity can be better controlled if a-alkoxystannanes are used as substrates. This modification is named the Wittig-Still Rearrangement . Here, the intermediate organolithium compound is produced through transmetallation ... 

The metalation of benzylamines is similarly interesting, because slight variations of the reaction conditions can significantly alter the regioselectivity of proton removal. Treatment of N,N-dimethylbenzylamine with organolithium compounds leads to dean ortho-metalation of the phenyl group [418, 431], If, however, phenyl-sodium [432] or mixtures of organolithium compounds and KOfBu [193, 209, 433]... 

Likewise, the first step in the synthesis of 50 is a regioselective ring opening of epoxide 40 with organolithium compound 45. By a series of manipulations, sulfone 47c is produced in 50% overall yield with 97% ee [11]. Ring opening of lactone 48 with the lithiated sulfone 47c... 

Athene synthesis. Alcohols can be alkylated or arylated by treatment with organolithium compounds and 1 (equation 1). The main interest in this synthesis is the reaction of allylic alcohols to form alkenes. The reaction is regioselective and stereoselective (inversion of configuration). 

Functionalizations via Silyl Hydride Functionalization and Hydrosilation A new general functionalization method based on the combination of living anionic polymerization and hydrosilation chemistry has been developed as illustrated in Scheme 7.26 [281]. First, a living polymeric organolithium compound is quantitatively terminated with chlorodimethylsilane to prepare the corresponding co-silyl hydride-functionalized polymer. The resulting co-silyl hydride-functionalized polymer can then react with a variety of readily available substituted alkenes to obtain the desired chain-end functionalized polymers via efficient regioselective transition-metal-catalyzed hydrosilation reactions [282-284]. 

The lithio-derivative of 2-phenylthioacetonitrile adds in a conjugate manner with high regioselectivity to cyclic enones. " Seebach reports that organolithium compounds undergo 1,4-addition to enones with sterically protected carbonyl groups in high yield [equation... 

Stadlwieser J, Barbler P, Taylor S (1998) 8-Fluoro-6-(methoxymethoxy)-quinoline synthesis and regioselective functionalization via reaction with organolithium compounds. Helv Chim Acta 81 1088-1094... 

The ease with which brominated heterocycles may be prepared regioselectively makes the use of these compounds as starting materials for the synthesis of regioselectively lithiated heterocycles extremely attractive. Organolithium derivatives of all the simple heterocycles at all possible positions of substitution have been made by this method.80 The scheme below illustrates some classical methods for forming 2-lithio-,81 3-lithio-,81 and 4-lithiopyridines,82 along with 4-lithioquinoline.83 rc-BuLi works well in these reactions, and indeed may be better than r-BuLi in reactions with electron deficient heterocycles, with which it tends to undergo addition reactions. 

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