Borane-catalysed imine reduction with hydrosilanes has been explored in the presence of water by means of reductive amination of carbonyls with amines, a reaction that produces equimolar amounts of imine and water, thus both are in large excess relative to the borane catalyst. In contrast to the perception that waterborane adducts are irreversibly deprotonated by amines/imines, poisoning the catalyst, B(C6F5)3 is actually a water-tolerant catalyst for the reductive amination of carbonyls with anilines, provided that the reaction mixture is heated in order to release sufficient free catalyst from [(C6F5)3BOH]- (upon reprotonation of the latter, followed by water dissociation). However, when the more basic alkylamines are employed, the poisoning of the catalyst (by [(C6F5)3BOH]- formation) is irreversible, thus preventing reductive amination of carbonyls with alkylamines. This problem could be overcome by employing less Lewis acidic boranes (e.g. BPh3 or B(3,5- C6H3Cl2)3) in order to form water-borane adducts less susceptible to irreversible deprotonation by alkylamines (or derived imines). However, water-borane adducts are not always undesirable since they can also act as strong Bronsted acids, and this property was utilised in the aldehyde-aniline-alkyne (A3) reaction to form substituted quinolines initiated by (C6F5)3B-OH2. Indeed, in this case mechanistic studies showed that Lewis acid catalysis by B(C6F5)3 was not operating, with the formation of (C6F5)3B-OH2 being crucial for Bronsted acid catalysis (as confirmed by replacing B(C6F5)3 with the strong acid HNTf2). Another approach to water-compatibility in FLP chemistry is the design of Lewis acids with reduced oxophilicity, relative to boranes, but with enough hydridophilicity to catalyse the reduction of unsaturated systems. A family of cationic carbon Lewis acids, namely N-methyl-benzothiazolium salts, has been synthesized and applied as Lewis acids. While active for dehydrosilylation of alcohols and hydrosilylation of C=X bonds (X = O, NR), they proved to be slower than the boranes widely used in silane activation. However, cationic carbon-based Lewis acids, namely N-methylacridinium salts, allowed for a rare example of a 1,2-hydrocarbation of alkynes when in combination with 2,6-lutidine. This alkyne functionalization is comparable to the well-established alkyne 1,2-hydroboration reaction, although this 1,2-hydrocarbation was shown to be mechanistically distinct, proceeding via a stepwise process. Finally, the design of water-tolerant Lewis acids has been achieved using electrophilic phosphonium cations through the synthesis and application of Ptrifluoromethyl phosphonium salts which showed tolerance to water, but not to water-base combinations.
|Date of Award||31 Dec 2018|
- The University of Manchester
|Supervisor||Michael Ingleson (Supervisor)|