Catalysis

In Tandem Enantioselective Intramolecular Heck-Matsuda Reactions directly from anilines

Authors

Abstract

A new enantioselective intramolecular strategy for the synthesis of enantioenriched bridged benzoxacines, unsaturated spirobenzofurans, methyl-2,3-dihydrobenzofuran acetates, and methyl-2,3-indoline acetate scaffolds in a tandem-like diazotization/Heck Matsuda process directly from anilines has been developed. The process combines the in situ diazotization of the aniline, followed by the intramolecular Heck-Matsuda reaction, thus skipping the isolation and purification of unstable or hard-to-synthesize aryldiazonium salts. The practicality and robustness of the sequence were demonstrated by the synthesis of 26 examples of complex structural motifs with yields up to 91% and enantiomeric ratio (er) up to 97:3, including quaternary stereocenters. The in-tandem processes from anilines were compared to conventional Heck Matsuda reactions using pre-synthesized aryldiazonium salts. With few exceptions, the reactions starting directly from the anilines afforded better overall yields and er, demonstrating the efficiency of this method.

Content

Thumbnail image of In Tandem Enantioselective Intramolecular Heck preprint 5b 14_09.pdf

Supplementary material

Thumbnail image of ESI preprint Sep 14 - Part 1-min.pdf
supplementary material 1
General experimental and synthesis of the substrates, General procedure for the one-pot enantioselective Eliminative intramolecular Heck-Matsuda; General procedure for enantioselective eliminative intramolecular Heck-Matsuda; General procedure for the one-pot enantioselective eliminative intramolecular Heck-Matsuda; General procedure for enantioselective eliminative intramolecular Heck-Matsuda; General procedure for the enantioselective carbonylation intramolecular Heck-Matsuda; Determination of the absolute configuration of key compounds; Characterization of Compounds, including chromatograms; References.
Thumbnail image of ESI preprint Sep 14 - Part 2.pdf
supplementary material 2
spectra of the Heck products. Part 2
Thumbnail image of ESI preprint Sep 14 - Part 3.pdf
supplementary material 3
spectra of the Heck products. Part 3
Thumbnail image of ESI preprint Sep 14 - Part 4.pdf
supplementary material 4
spectra of the Heck products. Part 4
Thumbnail image of ESI preprint Sep 14 - Part 5.pdf
supplementary material 5
spectra of the Heck products. Part 5
Thumbnail image of ESI preprint Sep 14 - Part 6.pdf
supplementary material 6
spectra of the Heck products. Part 6
Thumbnail image of ESI preprint Sep 14 - Part 7.pdf
supplementary material 7
spectra of the Heck products. Part 7
Thumbnail image of ESI preprint Sep 14 - Part 8.pdf
supplementary material 8
spectra of the Heck products. Part 8
Thumbnail image of ESI preprint Sep 14 - Part 9.pdf
supplementary material 9
spectra of the Heck products. Part 9
Thumbnail image of ESI preprint Sep 14 - Part 10.pdf
supplementary material 10
spectra of the Heck products. Part 10
Thumbnail image of ESI preprint Sep 14 - Part 11.pdf
supplementary material 11
spectra of the Heck products. Part 11