Enantioselective Organocatalytic Three-Component Petasis Reaction among Salicylaldehydes, Amines, and Organoboronic Acids

Abstract

The catalytic enantioselective three-component Petasis reaction among salicylaldehydes, amines, and organoboronic acids with a newly designed thiourea-binol catalyst is presented. A broad range of alkylaminophenols can be obtained in good yield (up to 92%) and good to high enantioselectivity (up to 95% ee). A possible reaction pathway for this catalytic enantioselective Petasis reaction is tentatively proposed.As a multicomponent reaction, 1 the Petasis reaction enjoys a history of nearly two decades and makes a significant contribution to the preparation of an assortment of compounds depending on the nature of the aldehyde component involved. 2 Among them, R-amino acids starting from glyoxylic acid and derivatives, R-hydroxyl amines starting from glycolaldehyde and derivatives, and alkylaminophenols starting from salicylaldehyde and derivatives are the most easily accessible. 3 In particular, studies on asymmetric induction by using various chiral reactants have achieved remarkable success in this area. 2b,2d,4 However, to date, there are only three examples concerning the catalytic enantioselective Petasis reaction reported by Takemoto 5 and Schaus, 6 respectively (Scheme 1, eqs 1À3). Notably, the three existing catalytic †

Multicomponent Mannich‐Like Reactions of Organometallic Species

“…Asymmetric versions of the reaction have also been investigated. Diastereoselective reactions have been achieved with N ‐ tert ‐butanesulfinamide and lactol derivatives, whereas enantioselective transformations were achieved with thiourea, binaphthol,, or mixed thiourea/binaphthol organocatalysts. The Petasis reaction has been used in the synthesis of aminophosphonic acid derivatives, α‐pyridinyl amines, pyrrolinol precursors, β,γ‐dehydrohomoarylalanines, tetrahydroisoquinoline precursors, tertiary amines (through a double reaction sequence), benzoxazine derivatives, and quinoxaline precursors, as well as in the total synthesis of cytoxazone, pyrrolizidine natural products, zanamivir, conduramine E, (–)‐steviamine, and legionaminic acid …”

BINOLs modified at 3, 3′-positions: chemists’ preferred choice in asymmetric catalysis

“…29 A wide range of alkylaminophenols can be obtained in good to high enantioselectivity (up to 95% ee) and good yield (up to 92%) (Scheme 12). Scheme12.…”

Enantioselective Synthesis of Triarylmethanes via Organocatalytic 1,6‐Addition of Arylboronic Acids to para‐Quinone Methides

“…[8,9] However, their applications in the preparation of chiral triarylmethanes via asymmetric aryl addition have been rarely investigated, probably due to the challenges in remote stereocontrol of p-QMs. Although aryl boronic acids, [16] arylboronate esters, [12c,e,14] and potassium organotrifluoroborates [15] have been used as aryl sources for this organocatalytic 1,4-aryl additions, limited substrate tolerances (preference for electron-rich arylboronates) were usually observed. Although aryl boronic acids, [16] arylboronate esters, [12c,e,14] and potassium organotrifluoroborates [15] have been used as aryl sources for this organocatalytic 1,4-aryl additions, limited substrate tolerances (preference for electron-rich arylboronates) were usually observed.…”

“…[8,9] However, their applications in the preparation of chiral triarylmethanes via asymmetric aryl addition have been rarely investigated, probably due to the challenges in remote stereocontrol of p-QMs. On the other hand, organoboron reagents participated asymmetric 1,4-additions [10][11][12][13][14][15][16][17] have been well developed in the last decades. Although aryl boronic acids, [16] arylboronate esters, [12c,e,14] and potassium organotrifluoroborates [15] have been used as aryl sources for this organocatalytic 1,4-aryl additions, limited substrate tolerances (preference for electron-rich arylboronates) were usually observed.…”

“…On the other hand, organoboron reagents participated asymmetric 1,4-additions [10][11][12][13][14][15][16][17] have been well developed in the last decades. Although aryl boronic acids, [16] arylboronate esters, [12c,e,14] and potassium organotrifluoroborates [15] have been used as aryl sources for this organocatalytic 1,4-aryl additions, limited substrate tolerances (preference for electron-rich arylboronates) were usually observed. To the best of our knowledge, there have been no report on the enantioselective organocatalytic 1,6-addition of arylboronic acids to p-QMs for the synthesis of chiral triarylmethanes.…”