Organocatalytic Enantioselective Acyl Transfer onto Racemic as well as meso Alcohols, Amines, and Thiols

Abstract

Acyl transfer is at the heart of functional-group transfers utilized both in nature and in the chemical laboratory. Acylations are part of the natural assembly machinery for the generation of complex molecules and for energy transport in biological systems. The recognition of covalent acyl-enzyme intermediates led to both mechanistic studies as well as the development of biomimetic approaches. Consequently, chemists first used the tools of nature in the form of enzymes and naturally occurring alkaloids as catalysts, before eventually developing a large variety of synthetic small molecules for selective acyl transfer. In contrast to nature, chemists utilize acylation reactions as a practical way for stereoselection and functional-group protection. Indeed, the number of studies concerning acyl transfer has significantly increased over the last 15 years. This Review examines and highlights these recent developments with the focus as given in the title.

Amines vs. N‐Oxides as Organocatalysts for Acylation, Sulfonylation and Silylation of Alcohols: 1‐Methylimidazole N‐Oxide as an Efficient Catalyst for Silylation of Tertiary Alcohols

“…[43,44] In conclusion, we have directly compared a series of five commonly used Lewis-basic amines (1)(2)(3)(4)(5) and three N-oxides (6-8) as catalysts for the acylation, sulfonylation and silylation of primary, secondary and tertiary alcohol derivatives 9a-c. Whilst the amine catalysts are generally more efficient in the acylation processes, the N-oxides are generally more effective catalysts in the analogous sulfonylation and silylation reactions. In particular, 1-methyl-imidazole-N-oxide (NMI-O) has been shown to be a highly efficient catalyst for the sulfonylation and silylation of alcohols and, importantly, the first effective non-phosphorus based Lewis-basic catalyst for the silylation of tert-alcohols with TES-Cl.…”

“…[1] A particular focus has been the development of chiral catalysts based on N-heterocycles, phosphines, N-heterocyclic carbenes and alcohols. [2][3][4][5][6][7][8][9] Whilst these catalysts have been primarily evaluated on their ability to impart enantioselectivity, the intrinsic Lewis basicity of their cores strongly impacts on their catalytic efficiency. Data relating to the efficiency of these catalophores [10] is generally inferred from the performance of the appropriate small molecule unsubstituted achiral Lewis bases.…”

“…We expected that pyridine-N-oxide and other N-oxides would also act as efficient catalysts for the formation of carboxylic esters, sulfonic esters and silyl ethers from alcohols and the appropriate acyl-, sulfonyl-and silyl chlorides, [21] and sought to benchmark their activity against the most commonly used Lewis-basic amine catalysts (Figure 1). Herein, we report the results of a systematic comparison of the performance of five amines (1)(2)(3)(4)(5) and three N-oxides (6)(7)(8) as catalysts for the acylation, sulfonylation and silylation of primary alcohol 9a, sec-alcohol 9b and tert-alcohol 9c using acyl chloride 10 (Table 1), sulfonyl chloride 12 (Table 2) and silyl chloride 14 (Table 3), respectively.…”

Aryloxide‐Facilitated Catalyst Turnover in Enantioselective α,β‐Unsaturated Acyl Ammonium Catalysis

“…Acyl ammonium and ammonium enolate intermediates have been extensively studied and applied in enantioselective acyl transfer processes and formal cycloadditions,respectively. [2,3] Aless studied but equally powerful reactivity mode is that of a,b-unsaturated acyl ammonium intermediates.[4] These species contain electrophilic centres at the C1 and C3 positions,a nd al atent nucleophilic centre at C2, providing new opportunities for reaction design to target previously inaccessible product architectures. [5] Seminal work by Fu first demonstrated the feasibility of this concept in af ormal [3+ +2] cycloaddition using a,bunsaturated acyl fluorides as the a,b-unsaturated acyl ammonium precursor (Scheme 1b).…”

“…Acyl ammonium and ammonium enolate intermediates have been extensively studied and applied in enantioselective acyl transfer processes and formal cycloadditions,respectively. [2,3] Aless studied but equally powerful reactivity mode is that of a,b-unsaturated acyl ammonium intermediates.…”