Unusual Ester‐Directed Regiochemical Control in endo‐Selective Asymmetric 1,3‐Dipolar Cycloadditions of Azomethine Ylides with β‐Sulfonyl Acrylates

Abstract

Scheme 4. Small models A and B to rationalize the regioselectivity.

Stereochemical diversity in pyrrolidine synthesis by catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides

“…16 In 2008 Wang and co-workers reported the first examples of endo selective silver catalyzed cycloaddition of vinyl phenyl sulfone using TF-BiphamPhos 15 as ligand (Scheme 3, Ca). 17 The scope of the sulfonyl dipolarophile was later expanded to -sulfonylacrylates (Scheme 3, Cb) 18 and 1,2-bisphenylsulfonyl ethylene (Scheme 3, Cc). 19 Although -iminoglycinates are the standard, typically used, azomethine precursors (R=H), substituted  iminoesters derived from other aminoacids, such as alanine, phenylalanine, valine, etc.…”

Asymmetric Synthesis of Quaternary α‐Amino Acids and Their Phosphonate Analogues

“…Asymmetric 1,3-dipolar cycloaddition of azomethine ylides generated from imines 109 (Scheme 31) with electron-deficient olefins provides easy access to highly substituted proline derivatives with an a-quaternary stereocenter. [47] In this context, the Wang group reported a highly regio-and endoselective asymmetric 1,3-dipolar cycloaddition of various aryl azomethine ylides (from 109) with (Z)-sulfonyl acrylate 108 in the presence of a chiral TF-BiphamPhos C33-Ag I complex, which provided a-quaternary proline derivatives 110 with contiguous quaternary-tertiary-tertiary-tertiary stereocenters in moderate to excellent yields and enantioselectivities with excellent endo-selectivities (Scheme 31). [47] The high regioselectivity of this reaction was directed by ester functional groups.…”

“…[47] In this context, the Wang group reported a highly regio-and endoselective asymmetric 1,3-dipolar cycloaddition of various aryl azomethine ylides (from 109) with (Z)-sulfonyl acrylate 108 in the presence of a chiral TF-BiphamPhos C33-Ag I complex, which provided a-quaternary proline derivatives 110 with contiguous quaternary-tertiary-tertiary-tertiary stereocenters in moderate to excellent yields and enantioselectivities with excellent endo-selectivities (Scheme 31). [47] The high regioselectivity of this reaction was directed by ester functional groups. Theoretical calculations suggested a stepwise mechanism, and that activation of sulfone and ester groups by hydrogen bonding with the free NH 2 group of C33 was responsible for the high diastereo-and enantioselectivities.…”

“…Theoretical calculations suggested a stepwise mechanism, and that activation of sulfone and ester groups by hydrogen bonding with the free NH 2 group of C33 was responsible for the high diastereo-and enantioselectivities. [47] In 2012, the groups of Carretero and Adrio introduced asilylimines 111 as 1,3-dipoles in an asymmetric 1,3-dipolar cycloaddition for the synthesis of enantioenriched 5-unsubstituted a-quaternary proline derivatives. [48] A Cu I complex of chiral DTBM-SEGPHOS C34 catalyzed the reaction between various alkyl-and aryl-substituted imines (111) and N-phenylmaleimide (61 a) to provide bicyclo a-quaternary proline derivatives 112 as single diastereomers in moderate to good yields with excellent enantioselectivities (Scheme 32).…”

Metal Complex‐Controlled Regio‐, Diastero‐ and Enantioselective 1,3‐Dipolar Cycloaddition of Azomethine Ylides with Benzo[b]thiophene Sulfones

“…It was amazing that the silver/ ThioClickFerrophosc omplex switched regioselectivity and diastereoselectivity.I ts regiochemistry was unusual and opposite that of the copper-catalyzed reaction, [10] and endo diastereoselectivity was consistent with the silver-catalyzed cycloaddition of azomethine ylide with vinyl phenyl sulfone. [11] The structure of 5ag was characterized by NMR spectroscopy and further confirmed by X-ray crystallography;i ts relative and absolute configuration was assigned as (1R,3 R,3aR,8bR). We were interestedi nt his regioselectivity-switch and tried to improvet he regioselectivity for 5ag by optimization experiments.T he resultso ft he optimization experimentsa re shown in Table 3.…”