Tetramethylammonium fluoride TMAF

Recently, Shibata, Tom, and coworkers demonstrated that a mixture of chiral ammonium bromides, 146 and 147, and tetramethylammonium fluoride (TMAF) [67] or KF [68] can be directly used as a catalyst without the need for the prior isolation of the fluoride salts. By utilizing this catalyst system, the reactions ofvarious aromatic ketones or aldehydes with (TMS)CF3 were completed within a few hours to afford the corresponding products in moderate to high enantioselectivities (Schemes 8.56 and 8.57). 

In 2006, Scheidt and coworkers [44] reported the first enantioselective direct nucleophilic addition ofthe silylated thiazolium salt 148, a precursor of the equivalent acyl anion, to nitroalkene 149 in the presence of tetramethylammonium fluoride (TMAF) and stoichiometric amounts of quinine-based thiourea 81b, producing the chiral [3-nitroketone 150 in 67% yield and with 74% ee (Scheme 9.51). The acyl anion equivalent 152 can be generated by the desilylation of 148 with TMAF, followed by the 1,2-H shift of the resulting alkoxide 151. The observed asymmetric induction indicates that there is a strong interaction between the thiourea and the nitroalkene during the carbonyl anion addition step. 

The addition of PhSeCF2TMS to carbohydrate-derived a-chiral aldehydes provided the corresponding difluoro(phenylselenyl)-methyl adducts with acceptable diastereoselectivities (eqs 9-15). Tetramethylammonium fluoride (TMAF) appeared as the appropriate mediator for these reactions (eqs 9-13 and eq 15). The benzoyl-protected aldehyde required the use of tetrabutylammo-nium difluorotriphenylsilicate (THAT) as a mediator to give the addition product only in low yield (eq 14). The two-step procedure (the addition of TBAF in the second step) was used to convert the OH/OTMS mixture initially obtained to the free alcohols (eqs 9 and 13-15). For benzyl- and MOM-protected aldehydes, a warm-up to room temperature was sufficient to afford alcohols in high yields (eqs 10-12). 

In some cases, less activated iV-aryl imines were transformed into the corresponding trifluoromethylamines by reaction with TMSCF3 in the presence of CsF and TMS-imidazole, or with fluoride initiators such as TBAT or TMAF (eq 14). However, in the latter example higher amounts of fluoride caused the loss of HF and therefore difluoromethylamines were obtained after reduction with NaBH4. When a stoichiometric amount of TMAF was employed, tetramethylammonium amides were formed and further treated with a variety of electrophiles to produce N-substituted trifluoromethylamines. IV-Methyl imines derived from salicyl-aldehydes reacted with TMSCF3 after forming an iminium cation (eq 15). 

---