Asymmetric Synthesis of 3,3-Diarylpropanals with Chiral Diene−Rhodium Catalysts

Abstract

A general route to enantioenriched 3,3-diarylpropanals is presented. These useful building blocks are prepared via an asymmetric rhodium-catalyzed conjugate addition of arylboronic acids to cinnamaldehyde derivatives in the presence of chiral dienes. The addition of both electron-poor as well as electron-rich boronic acids proceeds smoothly with various enals in 63-90% yield with high enantioselectivities (89-93% ee).

Rhodium‐ and Palladium‐Catalyzed Asymmetric Conjugate Additions

“…However, enals represent an especially challenging class of substrates in Rh-catalyzed ECAs [112,109,136]. This can be attributed to the high reactivity of aldehydes, which can undergo competitive 1,2-addition either in competition with (34) or after the 1,4-addition (33) (Scheme 1.19).…”

Chiral Bicyclo[3.3.0]octa‐2,5‐dienes as Steering Ligands in Substrate‐Dependent Rhodium‐Catalyzed 1,4‐Addition of Arylboronic Acids to Enones

“…A solution of KHMDS (1.32 g, 6.64 mmol) in THF (12 mL) was slowly added to a solution of (3aR,6aR)-7 (400 mg, 3.00 mmol) and N-(2-pyridyl)-bis(trifluoromethanesulfonimide) (2-PyNTf 2 ) (2.49 g, 6.96 mmol) in THF (12 mL) at À78 8C, and the reaction mixture stirred for 3 h. Then a saturated solution of NaHCO 3 (10 mL) was added. The aqueous layer was extracted with pentane (2 50 mL), the combined organic layers were washed with a solution of 5 % NaOH-H 2 According to this protocol the following addition products were obtained. The spectroscopic data of 13, 14 and 16a, 17a are in accordance with those in the literature.…”

“…This situation changed with the recent seminal work of Hayashi, [1] Carreira, [2] and Grützmacher. [3] Their work confirmed the successful application of chiral diene ligands 1, 2 based on bicycloalkanes, or tropylidenephosphane 3 (Scheme 1), resulting in high selectivities, [4] for example, in the Ir-catalyzed hydrogenation of imines [3d] and allylic substitution, [2c] in the Rh-catalyzed 1,4-addition of phenylboronic acid to enones [1h,l,2d] and fumarates [1k] or in the Rh-catalyzed aryl transfer to sulfonylimines.…”

Asymmetric Synthesis of Chiral Aldehydes by Conjugate Additions with Bifunctional Organocatalysis by Cinchona Alkaloids

“…Enantioselective transformations of the readily available prochiral aldehydes are now emerging as a fundamentally important approach toward optically active aldehydes. In particular, great strides have been made in the development of enantioselective bond formations with the a-carbon atom of prochiral aldehydes with chiral enamine catalysis, [1,2] enantioselective cycloadditions and Friedel-Crafts reactions with chiral immonium catalysis, [3] and conjugate additions of aryl boronic acids and silyl nitronates to a,b-unsaturated aldehydes by chiral transition-metal catalysis [4] and chiral phase-transfer catalysts, [5] respectively. Despite its synthetic importance, the highly enantioselective and general conjugate addition of carbonyl donors to a,b-unsaturated aldehydes remains elusive, even with considerable efforts.…”