Asymmetric Synthesis of New Chiral β-Amino Acid Derivatives by Mannich-type Reactions of Chiral N-Sulfinyl Imidates with N-Tosyl Aldimines

Abstract

New chiral beta-(sulfonylamino)sulfinylimidates are synthesized in high overall yield and excellent diastereomeric excess via highly anti-selective Mannich-type reactions of chiral N-tert-butanesulfinyl imidates with N-tosyl aldimines. Deprotection of the beta-(sulfonylamino)sulfinylimidates gave access to enantiopure imidate hydrochlorides in high yields, as useful intermediates for an easy transformation to new chiral beta-sulfonylamino amides upon simple heating in chloroform. Hydrolysis of the imidate hydrochlorides afforded the corresponding chiral beta-sulfonylamino esters with >98% ee as new chiral beta-amino acid derivatives.

Asymmetric Synthesis of δ‐Chloro‐β‐amino‐N‐sulfinyl Imidates as Versatile Chiral Building Blocks for the Synthesis of 2,3‐Disubstituted Piperidines

“…In conclusion, we have demonstrated that δ‐chloro‐β‐amino‐ N ‐sulfinyl imidates can be readily prepared by highly anti ‐selective Mannich‐type reactions of δ‐chloro‐ N ‐sulfinyl imidates across aromatic N ‐sulfonyl aldimines. The complete anti diastereoselectivity of this reaction to give δ‐chloro‐β‐amino‐ N ‐sulfinyl imidates is consistent with the stereochemical outcome observed for α‐methyl‐substituted imidates 15f. Subsequent cyclization and deprotection reactions led to the formation of various chiral 2,3‐disubstituted piperidines such as 3‐amino‐2‐arylpiperidines and 2‐arylpiperidine‐3‐carboxylic acid derivatives, which belong to a class of compounds with potent biological activity or are of interest as valuable building blocks.…”

“…The observed 2,3‐ anti diastereoselectivity of the addition reaction of N ‐sulfinyl imidate 8 across N ‐sulfonyl aldimines 9 can be rationalized by using a model in which the reaction proceeds via transition states TS‐1 and TS‐2 (Figure 2) with poor facial selectivity. Upon deprotonation of imidate 8 ,14c,15f the E ‐enolate, with the chloropropyl group and the N ‐ tert ‐butylsulfinyl group on opposite sides of the C–C double bond, will be preferentially formed. The N ‐sulfonyl aldimines (i.e., 9 ) adopt an E configuration.…”

“…In particular, N ‐( tert ‐butanesulfinyl)imidates are very useful chiral enolate precursors for Michael addition,16 α‐alkylation,17 and aldol addition 18. Recently, our group demonstrated asymmetric, highly anti ‐selective Mannich‐type reactions of α‐methyl‐ and α‐chloro‐ N ‐sulfinyl imidates across N ‐tosyl aldimines 15f,15g. These imidates were used in the synthesis of enantiopure β‐sulfonylamino amides and esters as new chiral β‐amino acid derivatives.…”

A simple and highly efficient solvent- and catalyst-free synthesis of novelN-sulfamoyl imines

“…As a consequence, N-sulfonyl imines have been widely used in various transformations in organic synthesis for access at biologically active compounds (6). They are excellent substrates in nucleophilic additions (7), Aza Diels-Alder reaction (8), reductions (9), oxaziridine (10) synthesis, asymmetric synthesis of β-amino acids derivatives (11), and reactive alkenes in ene reactions (12). In addition, they are excellent precursors for the preparation of optically active 2-imidazolines (13).…”

Solvent-free synthesis of N-sulfonyl imines using WCl6 as a novel, highly efficient and reusable catalyst

“…As a consequence, N-sulfonyl imines have been widely used in organic transformations. 2 Furthermore, they are excellent substrates in nucleophilic additions, 3 reductions, 4 aza Diels-Alder reactions, 5 alternative aziridine synthesis involving nucleophilic addition across N-sulfonyl aldimines, 6 asymmetric synthesis of b-amino acid derivatives, 7 and oxaziridine synthesis, 8 as well as ene reactions. 9 Several kinds of synthetic routes toward N-sulfonyl imines have been developed namely via the Lewis and protic acid catalyzed reactions of sulfonamides with aldehyde precursors, [10][11][12][13][14][15][16][17][18][19][20][21][22] rearrangement of oxime O-sulfinates, 23 tellurium mediated reaction of aldehydes with chloramine T by utilization of in situ generated N,N9-ditosyltellurodiimide, 24 application of N-sulfinyl sulfonamides instead of sulfonamides to generate sulfonyl imines in situ via a [2 + 2] cycloaddition and extrusion of sulfur dioxide, 25 generation of sulfonamidosulfones and basic elimination, 26,27 and catalyzed isomerization or rearrangement of N-sulfonyl aziridines.…”