Ammonium bromide preferential formation

Upon facing the difficulty of stereochemical control in peptide alkylation events, Maruoka and coworkers envisaged that the chiral phase-transfer catalyst should play a crucial role in achieving an efficient chirality transfer, and consequently examined the alkylation of the dipeptide, Gly-L-Phe derivative 57 (Scheme 5.28) [31]. When a mixture of 57 and tetrabutylammonium bromide (TBAB, 2 mol%) in toluene was treated with a 50% KOH aqueous solution and benzyl bromide at 0°C for 4h, the corresponding benzylation product 58 was obtained in 85% yield with the diastereo-meric ratio (DL-58 LL-58) of 54 46 (8% de). In contrast, the reaction with chiral quaternary ammonium bromide (S,S)-lc under similar conditions gave rise to 58 with 55% de. The preferential formation of LL-58 in lower de in the reaction with (R,R)-lc indicated that (R,R)-lc is a mismatched catalyst for this diastereofacial differentiation of 57. Changing the 3,3 -aromatic substituent (Ar) of the catalyst 1 dramatically increased the stereoselectivity, and almost complete diastereocontrol was realized with (S,S)-lg. 

The Neber route has been noted to be mildly influenced by the introduction of chiral auxiliaries. Thus, rearrangement of the tosyl oxime 860 (formed in situ from the oxime 859) in the presence of catalytic amounts of the chiral quaternary ammonium bromide 858 led to the formation of enantiomerically enriched amino ketone 863, which is presumed to arise from the preferential formation of the intermediate 2//-azirine 862. Association of the cationic chiral auxiliary with an anionic intermediate (i.e, 861) has been invoked to rationalize the stereochemical outcome (Scheme 215) <2002JA7640>. 

The use of mixtures of sodium hydroxide and benzyltrimethylammonium chloride or tetrabutylammonium bromide failed to enhance the DPGE alkylation of HEC by the in situ formation of the corresponding quaternary ammonium hydroxide phase transfer catalyst. These quaternary ammonium halides are too soluble in aqueous /-butyl alcohol and are preferentially extracted into the organic phase. Mixtures of benzyltrimethylammonium hydroxide and sodium acetate were also ineffective in enhancing the DPGE alkylation of HEC for the same reason, namely preferential solubility of benzyltrimethylammonium acetate in the organic phase. 

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