Carbene‐Catalyzed Enantioselective Hydrophosphination of α‐Bromoenals to Prepare Phosphine‐Containing Chiral Molecules

Abstract

Disclosed herein is the first carbene-organocatalyzed asymmetric addition of phosphine nucleophiles to the in situ generated a,b-unsaturated acyl azolium intermediates. Our reaction enantioselectively constructs carbon-phosphine bonds and prepares chiral phosphines with high optical purities. The phosphine products are suitable for transforming to chiral ligands or catalysts with applications in asymmetric catalysis. The diarylalkyl or trialkyl phosphine products from our catalytic reactions, air-sensitive and reactive in nature, can be trapped (and stored) in their sulfur-oxidized form for operational simplicities.

Divergent Mechanistic Pathways for Copper(I) Hydrophosphination Catalysis: Understanding That Allows for Diastereoselective Hydrophosphination of a Tri-substituted Styrene

“…Organophosphines are integral molecules in catalysis, synthetic chemistry, materials science, and more. − Metal-catalyzed hydrophosphination, the addition of a P–H bond across an unsaturated substrate, is one of the most promising and atom-economical P–C bond-forming reactions. − Progress has been made in expanding the available catalysts, scope, and selectivity of hydrophosphination in recent years. − However, limitations remain that hamper the synthetic utility of hydrophosphination. , Among the most notable limitations with known catalysts is that they often require special preparation and/or complex ancillary ligands and that most precatalysts are not air- and water-stable (i.e., not convenient). Known catalysts also have limitations in reactivity, often stymied by unactivated or highly substituted substrates, especially in intermolecular reactions. , …”

Synthesis of P-stereogenic cyclicphosphinic amidesviaelectrochemically enabled cobalt-catalyzed enantioselective C–H annulation

“…Chiral phosphorus compounds containing P-stereogenic centers are not only present in numerous bioactive natural products, pharmaceuticals, and polymer materials, 1 but also widely utilized as chiral ligands or directly as organocatalysts for diverse asymmetric transformations. 2 Due to their significant importance, enormous amounts of energy have been poured into the exploration of efficient asymmetrical synthesis approaches, 3 such as asymmetrical cross-coupling, 4 enantioselective nucleophilic substitution, 5 desymmetrization, 6 asymmetrical addition, 7 transition metal-catalyzed enantioselective C–H activation 8 and so on, 9 for assembling valuable P-stereogenic compounds. Despite these advances, the development of more step-economic and environmentally friendly methodologies is still of great and abiding interest.…”

Enantioselective copper-catalyzed hydrophosphination of alkenyl isoquinolines

“…Pd-Catalyzed asymmetric hydrophosphination of α,β-unsaturated compounds (including α,β-unsaturated aldehydes, ketones, esters, pyrrole amides, sulfonic esters, and sulfonamides) with secondary phosphines has emerged as a versatile method for the construction of chiral phosphine compounds ( Scheme 1a ). 4 Other transition metal complexes such as chiral Ni, 5 Pt, 6 Cu 7 and Mn 8 catalysts and organocatalysts 9 were also applied in the asymmetric hydrophosphination of electron-deficient alkenes, recently. However, examples where heteroarenes were employed in alkene activation have not appeared due to the relatively poor reactivity of alkenylheteroarenes.…”