Direct Conversion of Primary Alcohols to 1,2-Amino Alcohols: Enantioselective Iridium-Catalyzed Carbonyl Reductive Coupling of Phthalimido-Allene via Hydrogen Auto-Transfer

Abstract

The first catalytic enantioselective carbonyl (α-amino)allylations are described. Phthalimido-allene 1 and primary alcohols 2a−2z, 2a′−2c′ engage in hydrogen auto-transfer-mediated carbonyl reductive coupling by way of (α-amino)allyliridium−aldehyde pairs to form vicinal amino alcohols 3a−3z, 3a′−3c′ with high levels of regio-, anti-diastereo-, and enantioselectivity. Reaction progress kinetic analysis and isotopic labeling studies corroborate a catalytic cycle involving turnover-limiting alcohol dehydrogenation followed by rapid allene hydrometalation.

Diastereodivergent Synthesis of β‐Amino Alcohols by Dual‐Metal‐Catalyzed Coupling of Alkoxyallenes with Aldimine Esters

“…reported elegant reductive coupling reactions of azadienes and ketones to access anti ‐β‐amino tertiary alcohols [5a] . Krische and co‐workers enantioselectively synthesized anti ‐β‐amino alcohols by reductive coupling reactions of phthalimidoallenes and aldehydes, which proceed via a hydrogen auto‐transfer process [5b] . Despite these achievements, none of the existing methods provide access to both syn ‐ and anti ‐β‐amino alcohols.…”

Empowering alcohols as carbonyl surrogates for Grignard-type reactions

“…In contrast, alcohols are among the most naturally abundant functional groups, which are commonly found in biomass and natural products. The direct transformation of alcohols into C-C bonds has been a long pursuit of synthetic chemists [8][9][10][11] . This type of transformation would be an especially vital tool for the latestage functionalization of alcohol-containing natural products and pharmaceuticals.…”

Access to a Catalytically Generated Umpolung Reagent through the Use of Cu-Catalyzed Reductive Coupling of Ketones and Allenes for the Synthesis of Chiral Vicinal Aminoalcohol Synthons

“…Chiral 1,2-aminoalcohols [ 1 (Figure 1)] make up an important class of biologically active compounds prevalent in nature and the pharmaceutical industry. 1 A recent publication 2 states that there are currently >300000 compounds, >2000 natural products, and >80 Food and Drug Administration-approved drugs bearing this motif. As a result, the development of asymmetric methods for preparing 1,2-aminoalcohols is an important endeavor in organic chemistry.…”

“…Such a process would represent a catalytic stereoselective aminoallylation reaction that is only recently beginning to emerge. 2,10,11 The results of our study to enable a diastereoselective synthesis of 1,2-aminoalcohol synthon b - 12 by use of an N-heterocyclic carbene (NHC)-derived Cu catalyst are disclosed herein.…”