Diastereo‐ and Enantioselective Iridium‐Catalyzed Carbonyl Propargylation from the Alcohol or Aldehyde Oxidation Level: 1,3‐Enynes as Allenylmetal Equivalents

Abstract

Carbonyl propargylation has been the topic of intensive investigation for over half a century. [1,2] An effective approach to enantioselective carbonyl propargylation involves the addition of chirally modified allenylmetal reagents, [3][4][5][6][7] including axially chiral derivatives. [5] Contributions include allenylboron reagents that are chirally modified at boron, as reported by Yamamoto, [3a] Corey, [3b] and Soderquist, [3c,d] allenylstannanes that are chirally modified at tin, as first reported by Mukaiyama, [4] as well as axially chiral allenylstannanes, allenylsilanes, allenylboron, and allenylzinc reagents that engage aldehydes in enantioselective propargylation, as described by Marshall, [5a,b,e,f] Hayashi, [5d] and Panek, [5c] respectively. Increasingly effective protocols for carbonyl propargylation, which involve stoichiometric chirality transfer, continue to be developed. [6,7] Enantioselective aldehyde propargylation using allenyltin [8] and allenylsilicon [9] reagents may be catalyzed by chiral Lewis acids or chiral Lewis bases, as first reported by Keck [8a] and Denmark, [8f] respectively. Copper catalysts promote enantioselective carbonyl propargylation by employing allenylboron and propargylboron reagents, as reported by Kanai and Shibasaki and Boehringer-Ingelheim Pharmaceuticals Inc. [10] More recently, Schaus, Antilla, and Reddy reported chiral H-bond donor and Brønsted acid catalyzed propargylations using allenylboron reagents. [11] Finally, catalytic enantioselective Nozaki-Hiyama coupling of propargyl halides delivers products of carbonyl propargylation. [12] Withstanding the Nozaki-Hiyama protocol, [12] methods available for enantioselective carbonyl propargylation have relied on stoichiometric allenylor propargylmetal reagents. Moreover, while carbonyl propargylations for the construction of non-methylated polyacetate subunits are common, catalytic diastereo-and enantioselective propargylations that convert achiral reactants to polypropionate substructures remain undeveloped. We envisioned an alternative strategy for carbonyl propargylation based on the "transfer hydrogenative coupling" [13] of 1,3-Angewandte Chemie

Catalytic Enantioselective Carbonyl Allylation and Propargylation via Alcohol-Mediated Hydrogen Transfer: Merging the Chemistry of Grignard and Sabatier

“…Using the chiral iridium catalyst generated from [Ir(cod)Cl] 2 and ( R )-DM-SEGPHOS, 1,3-enynes exchange hydrogen with primary alcohols to generate allenyliridium-aldehyde pairs that combine to form enantiomerically enriched products of carbonyl anti -(α-methyl)propargylation (Scheme 6-A). 30 In this process, the axial chirality of DM-SEGPHOS is transmitted to the axial chirality of the allenyliridium intermediate and, ultimately, the central chirality of the product. Similarly, silyl-terminated propargyl chlorides react with primary alcohols in the presence of the cationic iridium complex {Ir(cod)[( R )-SEGPHOS]}OTf to form enantiomerically enriched homopropargyl alcohols (Scheme 6-B).…”

Metal-catalyzed reductive coupling of olefin-derived nucleophiles: Reinventing carbonyl addition

“…Metals other than ruthenium catalyze enyne-carbonyl reductive coupling. For example, an iridium catalyst with ( R )-SEGPHOS or ( R )-DM-SEGPHOS ligands catalyzes highly enantioselective enyne-carbonyl reductive coupling from the alcohol or aldehyde oxidation level (42). In the latter case, formic acid serves as terminal reductant.…”

Engaging Aldehydes in CuH‐Catalyzed Reductive Coupling Reactions: Stereoselective Allylation with Unactivated 1,3‐Diene Pronucleophiles

“…[1] Accordingly,t he development of methods to accomplish this transformation in acatalytic,stereoselective manner has been the subject of widespread research efforts. [3][4][5][6][7][8][9][10] Following pioneering work by the group of Krische using Rh, [4a,b] Ru, [5] Ir, [6] and Ni catalysts, [7e] several research groups,including ours,have developed anumber of CuH-catalyzed processes for reductive CÀCb ond formation from p-unsaturated pronucleophiles. [3][4][5][6][7][8][9][10] Following pioneering work by the group of Krische using Rh, [4a,b] Ru, [5] Ir, [6] and Ni catalysts, [7e] several research groups,including ours,have developed anumber of CuH-catalyzed processes for reductive CÀCb ond formation from p-unsaturated pronucleophiles.…”