Stereoselectivity Control in the Rh(I)-Catalyzed Conjugate Additions of Aryl and Alkenylboronic Acids to Unprotected Hydroxycyclopentenones

Abstract

[reaction: see text] The stereoselective Rh(I)-catalyzed conjugate addition reaction of aryl and alkenylboronic acids to unprotected 2-phenyl-4-hydroxycyclopentenone is presented. The free OH group on the substrate is responsible for the stereochemistry, which is cis for arylboronic derivatives. In the case of the alkenylboronic compounds, the stereochemistry can be tuned to either a cis (bases as additives) or trans addition (CsF as additive) without the need of protecting groups.

Strategy of total synthesis based on the use of Rh-catalyzed stereoselective 1,4-addition

“…9 The product 6 of this Hayashi-Miyaura reaction was obtained as a single stereoisomer in high yield (Scheme 3). Since its isolation, many approaches have been proposed to prepare this compound in the most efficient way, but also to provide access to analogs for biological studies.…”

1,2‐Stereochemical Induction in the PdII‐Catalyzed Conjugate Addition of Boronic Acids

“…[6] In particular, the transition-metal-catalyzed conjugate addition of boronic acids and their derivatives to α,βunsaturated carbonyl compounds, the Hayashi-Miyaura reaction, has been extensively developed. [13] These reactions gave rise to a variety of interesting intermediates with a diverse range of scaffolds. [7,8] Nevertheless, because of the high price of Rh, alternative catalysts with less expensive transition metals have also been pursued.…”

Stereoselective conjugate addition of organolithium reagents to unprotected 4-hydroxy-2-cyclopentenones

“…In a similar fashion, conjugate addition of aryl and alkenyl groups to compounds 4 has been possible by using boronic acids in combination with Rh(I)-catalysis. 4 However, it is worth mentioning that the direct addition of alkyl or aryllithiums (2.0 equiv.) to compounds 4 gives rise to the products of direct addition to the carbonyl group 6 (1,2-addition) (Scheme 2).…”

“…The mixture was stirred 30 minutes and then, a 1.5 M solution of t BuLi in pentane (113 µL, 0.17 mmol) was added. The mixture was stirred for 18 h at room temperature and hydrolyzed with saturated NH 4 Cl solution (0.5 mL). The organic layer was decanted and the aqueous layer extracted with Et 2 O (3 x 5 mL).…”

“…The organic layer was decanted and the aqueous layer extracted with Et 2 O (3 x 5 mL). The combined organic layers were dried on MgSO 4 , filtered, and concentrated in vacuo. Purification was carried out by chromatography with hexane/ethyl acetate (1:2) as the eluent, giving rise to compounds 5.…”