Enantioselective Conjugate Addition of Alkenylboronic Acids to Indole-Appended Enones

Abstract

An enantioselective addition of alkenylboronic acids and alkynylboronic esters to unprotected indole-appended enones is reported. This transformation proceeds with high enantioselectivity and high product yields via the use of catalytic amounts of 3,3'-bis(pentafluorophenyl)-BINOL and Mg(Ot-Bu)(2). A range of α-branched indole derivatives are available from the transformation.

Asymmetric Organocatalytic C‐C Bond Forming Reactions with Organoboron Compounds: A Mechanistic Survey

“…In 2011, May and co-workers demonstrated that the novel (R)-3,3′-bis(pentafluoro-phenyl)-BINOL (R)-30 organocatalyzed the addition of alkenylboronic species 20 to indole-appended enones 29 (Scheme 7). [26] The methodology provides the 1,4-Scheme 6. DFT study of the 1,4-addition of alkenylboronates to enones mediated by chiral BINOL (R)-11.…”

“…In 2011, May and co‐workers demonstrated that the novel ( R )‐3,3′‐bis(pentafluoro‐phenyl)‐BINOL ( R )‐ 30 organocatalyzed the addition of alkenylboronic species 20 to indole‐appended enones 29 (Scheme ) . The methodology provides the 1,4‐addition products 31 with very good yields (60–91 %) and ees (87–99 %).…”

Biomimetic Synthesis and Studies Toward Enantioselective Synthesis of Flindersial Alkaloids

“…Our method creates a stereocenter at the benzylic position of the indole by the addition of alkenyl and akynyl boronates catalyzed by a BINOL catalyst . In order to design and evaluate a new catalyst for use with indoles, 3,3ʹ‐dipentafluorophenyl binaphthol and 3,3ʹ‐diiodo binaphthol were used in reactions with a 3‐enone substituted indole and 2‐cis‐butenylboronic acid (Scheme ).…”

Enantioselective magnesium-catalyzed transformations

“…To address the lack of such methods, May et al have employed a chiral magnesium catalyst in situ generated from Mg(Ot-Bu) 2 and (R)-BINOL-derived fluorinated ligand 156 to promote the Michael addition of vinyl nucleophiles, such as (E)-alkenylboronic acids 157, to indole-appended α,β-unsaturated ketones 158. 75 As shown in Scheme 43, the reaction led to the corresponding chiral α-branched indole derivatives 159 in good to high yields (70-91%) and uniformly high enantioselectivities (87-99% ee). An unprotected indole was not necessary for the reaction, as both Boc-and methyl-protected indoles (X = Boc, Me) reacted smoothly with high yields (85-86%) and excellent enantioselectivities (97-98% ee).…”