Catalytic Asymmetric Iterative/Domino Aldehyde Cross-Aldol Reactions for the Rapid and Flexible Synthesis of 1,3-Polyols

We
report here catalytic asymmetric iterative and domino cross-aldol
reactions between aldehydes, endowed with a high level of robustness,
flexibility, and generality. A Cu­(I)-DTBM-SEGPHOS complex catalyzes
an asymmetric cross-aldol reaction between acceptor aldehydes and
boron enolates derived from donor aldehydes, which are generated through
Ir-catalyzed isomerization of allyloxyboronates. The unit process
can be repeated using the aldol products in turn as acceptor substrates
for the subsequent asymmetric aldol reaction. The donor aldehydes
and stereoselectivity can be flexibly switched in a stepwise manner
for the double-aldol reaction. Furthermore, asymmetric triple- and
quadruple-aldol reactions are possible in one-pot using the appropriate
amounts of donors and amine additives, rapidly elongating the carbon
skeleton with controlling up to eight stereocenters. The method should
be useful for straightforward synthesis of enantiomerically and diastereomerically
enriched 1,3-polyols.