Substitution Reactions

Abstract

One of the prime virtues of carbanion chemistry is the diversity of reactions possible: Grignard-type, aldol and Michael additions, oxidative dimerization as well as substitution processes at sp3 and sp2 hybridized C-atoms [1], In case of the latter reactions, “resonance-stabilized” species such as ester and ketone enolates (and the nitrogen analogs), lithiated sulfones, sulfoxides, nitriles, etc. as well as hetero-atom-substituted reagents undergo smooth SN2 reactions with primary and some secondary alkyl halides and tosylates. A synthetic gap becomes apparent upon attempting to perform these reactions with tertiary alkyl halides and certain base sensitive secondary analogs, because they are not SN2 active. A similar situation arises in case of carbon nucleophiles lacking additional functionality. For example, (CH3)2CuLi and higher order cuprates undergo smooth substitution reactions with primary and most secondary alkyl halides, but not with tertiary analogs. It turns out that in many cases these problems can be solved using titanium chemistry (Section 7.1). Certain titanium reagents also allow for the combination of two processes in a one-pot sequence, namely addition to carbonyl compounds followed by SNl-type substitution of the oxygen function (Section 7.2.1). Conversely, titanium reagents are generally not nucleophilic enough to undergo SN2-reactions with primary alkyl halides.