Information Technology Laboratory technical accomplishments 1997

Interrogation of a dynamic multi-catalyst ensemble in asymmetric catalysis

“…Using a two-fold excess of MCHE 2 over 4, we studied the effect of additives on the reaction. A particularly surprising result came from the addition of NaBAr 0 F to the reaction catalysed by [5] + . For reasons outlined later, the selectivity of alkylation of 4 by NaCHE 2 to give 6 catalysed by 1 mM [5][Cl] is higher (87% ee) than that arising from 1 mM [5][BAr 0 F] (46% ee).…”

“…A particularly surprising result came from the addition of NaBAr 0 F to the reaction catalysed by [5] + . For reasons outlined later, the selectivity of alkylation of 4 by NaCHE 2 to give 6 catalysed by 1 mM [5][Cl] is higher (87% ee) than that arising from 1 mM [5][BAr 0 F] (46% ee). We had anticipated that systematic addition of NaBAr 0 F (0 to 10 mM) to the reaction catalysed by [5][Cl] would simply result in abstraction of the chloride from [5][Cl] to generate [5][BAr 0 F] in situ, thus reducing the ee from 87 to 46%.…”

“…For reasons outlined later, the selectivity of alkylation of 4 by NaCHE 2 to give 6 catalysed by 1 mM [5][Cl] is higher (87% ee) than that arising from 1 mM [5][BAr 0 F] (46% ee). We had anticipated that systematic addition of NaBAr 0 F (0 to 10 mM) to the reaction catalysed by [5][Cl] would simply result in abstraction of the chloride from [5][Cl] to generate [5][BAr 0 F] in situ, thus reducing the ee from 87 to 46%. However, the selectivity was much more substantially reduced, becoming 0% at 2 mM NaBAr 0 F and then inverting to progressively reach 10% ee (R)-6 at 10 mM NaBAr 0 F, Fig.…”

“…To test the stereochemical outcome of alkylation of the h 3 -C 6 H 9 -Pd(2) cation [5] + , independent of whether it is generated from (S)-4 or (R)-4, we conducted stoichiometric reactions of the isolated complexes 5[BAr 0 F], 5[OTf] and 5[Cl] with excess NaCHE 2 , and with excess Bu 4 NCHE 2 . Reactions conducted at low concentrations of [5] + (1 mM) gave (S)-6 in enantiomeric excesses that perfectly reflected the selectivities obtained with the faster-reacting matched enantiomer of substrate (S)-4 under catalytic conditions, thus supporting the proposed dominant catalytic flux of (S)-4 via the h 3 -C 6 H 9 -Pd(2) cation [5] + . 11 On increasing the concentration of the electrophile [5] + that was alkylated, a number of interesting changes in selectivity occurred.…”

“…2,3,6 Ligand 2 has been employed in the asymmetric synthesis of a plethora of natural products and both enantiomers of 2 are commercially available. 5 What distinguishes reactions catalysed by 'Pd(2)' from other Pd-catalysed allylations is the extraordinary sensitivity that the system has to the exact reaction conditions. 6,7 Thus, changes of solvent, temperature, nucleophile counter-ion, precatalyst counter-ion, Pd/ligand ratio, concentration, and nucleofuge, can all result in profound changes in enantioselectivity; as can the effect of additives such as halide.…”