Organocatalytic enantioselective methodologies using Morita–Baylis–Hillman carbonates and acetates

Abstract

Lately, the use of Morita-Baylis-Hillman carbonates and acetates in organocatalysis has grown exponentially. Since the pioneering work of Kim and coworkers until the last cycloadditions reported by Barbas, a plethora of new methodologies have been developed. The use of these compounds opens a new gate for the synthesis of C-C or C-heteroatom bonds in an enantioselective fashion and under mild conditions giving access to highly functionalized structures. In this review, we aim to cover these exciting reactions, paying special attention on the nature of the MBH adduct.

Organocatalyzed Decarboxylative Trichloromethylation of Morita–Baylis–Hillman Adducts in Batch and Continuous Flow

“…The idea was to apply simple acetylation as means of activating the Morita–Baylis–Hillman starting materials (Figure ). Upon reaction with an organocatalyst, such as 4‐dimethylaminopyridine (DMAP), the known intermediate A would be in equilibrium with the starting material ,. Towards introduction of the nucleophile, it was decided to upgrade trichloroacetate precursors to their corresponding trichloromethyl anions through decarboxylation .…”

Asymmetric allylic alkylation of Morita–Baylis–Hillman carbonates with α-fluoro-β-keto esters

“…Lewis base-catalyzed asymmetric allylic alkylations (AAA) of Morita–Baylis–Hillman (MBH) adducts [5–6], such as acetates and carbonates, have become an attractive option to access various chiral C - [7–19], N - [20–25], O - [26–30], P - [31–33] and S -allylic [34] and spirocyclic compounds [35–37]. Several protocols have been established to introduce fluorine atoms in AAA of MBH adducts.…”

Total Synthesis of Biologically Active Natural Products Based on Highly Selective Synthetic Methodologies

“…After our discovery of this β-ICD-HFIPA method, a number of sophisticated catalytic systems were developed. [1][2][3][4][5][6] This β-ICD-HFIPA method is applicable to chiral α-amino aldehydes 7 that afford the synthetically useful α-methylene-β-hydroxy-γ-amino acid esters 8 11) (Chart 4). It was found that β-ICD-catalyzed reactions of N-Boc-α-amino aldehydes 7 with HFIPA proceeded without racemization to give enantiomerically pure esters 8 and exhibited a marked match-mismatch relationship.…”

“…Compound 116 was then converted to 118 via 117 in a six-step sequence involving methylation, iodination, and diimide reduction as major transformations. Iodoalkene 118 was then subjected to Stille coupling with stannane 119 111) using Pd(PPh 3 ) 4 , CuI, and CsF in DMF at room temperature to give Z,Z,E-triene 120 in geometrically pure form. When this coupling was carried out using Pd(0) catalyst alone, some extent of isomerization of the triene system was always observed.…”

“…However, the major problems associated with this reaction are its slow reaction rate and difficulty in achieving a high level of asymmetric induction. [1][2][3][4][5][6] 2.1.1 Development of the β-Isocupreidine-Hexafluoroisopropyl Acrylate Method [7][8][9] In 1999, we achieved the first breakthrough in the catalytic asymmetric MBH reaction employing β-isocupreidine (β-ICD) as a chiral bifunctional catalyst and 1,1,1,3,3,3-hexafluoroisopropyl acrylate (HFIPA) as an activated alkene (β-ICD-HFIPA method) 7) (Chart 2). The reactions were carried out using 0.1 eq.…”