Stereodivergent Coupling of Aldehydes and Alkynes via Synergistic Catalysis Using Rh and Jacobsen’s Amine

Abstract

We report an enantioselective coupling between α-branched aldehydes and alkynes to generate vicinal quaternary and tertiary carbon stereocenters. The choice of Rh and organocatalyst combination allows for access to all possible stereoisomers with high enantio-, diastereo-, and regioselectivity. Our study highlights the power of catalysis to activate two common functional groups and provide access to divergent stereoisomers and constitutional structures.

Enantioselective Chemo‐ and Biocatalysis: Partners in Retrosynthesis

“…[266] Crucial to the realization of this method was the observation that the chiral phosphoramidite ligand 253 and the chiral amine 254 independently set the stereocenters in the a-a nd b-position, respectively,without exercising asignificant intrinsic matched bias for the other stereocenter.Asanalternative to Carreiras dual catalytic system, products such as (S,S)-255 and (R,S)-255 can also be synthesized following Dongsr ecently reported stereodivergent coupling of aldehydes and alkynes, catalyzed by ac hiral Rh-complex and Jacobensc hiral amine. [267] Another breakthrough in the area of stereodivergent catalysis was achieved by Hartwig who recently disclosed an allylic substitution with aryl acetic acid esters. [268] This approach rests on the ability of ac hiral Ir-complex and ab enzotetramisole catalyst to independently set two stereocenters.Inaddition to these approaches,anumber of elegant dual catalytic systems have been developed recently,demonstrating the increasing interest in stereodivergent catalytic methods.…”

Direct Enantioselective α‐Allylation of Unfunctionalized Cyclic Ketones with Alkynes through Pd‐Amine Cooperative Catalysis

“…Based on the important precedents on transition metal–amine dual catalysis, we propose a similar cooperative catalytic cycle in Scheme .…”

A Regio‐ and Stereodivergent Synthesis of Homoallylic Amines by a One‐Pot Cooperative‐Catalysis‐Based Allylic Alkylation/Hofmann Rearrangement Strategy

“…Noteworthy is the tolerance of aryl halides (5, 7, 8,a nd 10)e lectron-rich arenes (2)(3)(4)6), and p-extended arenes (9 and 10)t ot his oxidative protocol. Finally,b oth conjugated and non-conjugated alkene-substituted esters were effective (see products [11][12][13][14]; significant is the preparation of 14,w hich is chiral only by virtue of the alkene position. As yet, we have been unsuccessful in our attempts to engage either aliphatic esters or terminal alkyl-substituted electrophiles in this chemistry; both are the subject of ongoing study.…”

“…As part of al ong-standing program directed towards catalyzed and stereocontrolled carbon-carbon bond formation, we sought to provide as traightforward, operationally trivial, and modular-catalysis-based protocol for the regioand stereodivergent [12] synthesis of enantioenriched homoallylic amines. [13] Principal among our concerns was catalyst control over all aspects of selectivity during carbon-carbon bond formation, whilst also working within au seful N-protecting group regime.H erein, we describe such ap rotocol, which provides as traightforward and modular preparation of these valuable building blocks.…”