S- and P-Stereogenic heterocycles were synthesized by a remarkably simple enantioselective Heck desymmetrization reaction based on the unprecedented noncovalent directing effect of S=O and P=O functionalities. Selected prochiral symmetric substrates were efficiently arylated using the recently disclosed chiral PyraBOx ligand under mild and open-flask reaction conditions. Several five-membered aryl- sulfones, sulfoxides, and phosphine oxides were synthesized in good to excellent yields, in good to high diastereoselectivity, and enantiomeric ratios up to 98:2. Theoretical calculations also support the noncovalent directing effect of the S=O and P=O functionalities during the arylation process.
A new enantioselective intramolecular strategy for the synthesis of enantioenriched bridged benzoxacines, unsaturated spirobenzofurans, 2,3‐dihydrobenzofuran and 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 potentially unstable or hard‐to‐synthesize aryldiazonium salts. The practicality and robustness of the sequence were demonstrated by the synthesis of 30 complex motifs in yields up to 91% and enantiomeric ratios 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 enantioselectivity, demonstrating the efficiency of the method.
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.
Arenediazonium salts represent an important class of aromatic organic compounds widely used as building blocks in academia and industry. Due to the high energy associated with the diazonium group, many of these salts are reported as thermally unstable and/or unsafe to work with. However, most of the tetrafluoroborate arenediazonium salts, are fairly stable to handle at room temperature both in solution and when dry. Nevertheless, some of these salts, especially those containing heteroatoms in the aromatic moiety, present difficulties in their synthesis, and some are indeed highly unstable. To bring some light to this controversial subject, the thermal stability and potential hazards of the 57 most common arenediazonium tetrafluoroborate salts used in our laboratory over the last two decades were evaluated under careful conditions. These results are expected to guide important decisions on the use of arenediazonium tetrafluoroborates in organic synthesis.
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