Libraries of Bisdiazaphospholanes and Optimization of Rhodium-Catalyzed Enantioselective Hydroformylation

Twelve chiral bis-3,4-diazaphospholane
ligands and six alkene substrates
(styrene, vinyl acetate, allyloxy-tert-butyldimethylsilane,
(E)-1-phenyl-1,3-butadiene, 2,3-dihydrofuran, and
2,5-dihydrofuran) probe the influence of steric bulk on the activity
and selectivity of asymmetric hydroformylation (AHF) catalysts. Reaction
of an enantiopure bisdiazaphospholane tetraacyl fluoride with primary
or secondary amines yields a small library of tetracarboxamides. For
all six substrates, manipulation of reaction conditions and bisdiazaphospholane
ligands enables state-of-the-art performance (90% or higher ee, good
regioselectivity, and high turnover rates). For the nondihydrofuran
substrates, the previously reported ligand, (S,S)-2, is generally most effective. However,
optimal regio- and enantioselective hydroformylation of 2,3-dihydrofuran
(up to 3.8:1 α-isomer/β-isomer ratio and 90% ee for the
α-isomer) and 2,5-dihydrofuran (up to <1:30 α-isomer/β-isomer
ratio and 95% ee for the β-isomer) arises from bisdiazaphospholanes
containing tertiary carboxamides. Hydroformylation of either 2,3-
or 2,5-dihydrofuran yields some of the β-formyl product. However,
the absolute sense of stereochemistry is inverted. A stereoelectronic
map rationalizes the opposing enantiopreferences