Nickel-Catalyzed Enantioselective Carbamoyl Iodination: A Surrogate for Carbamoyl Iodides

Abstract

This work reports the enantioselective formal transfer of a carbamoyl iodide across a 1,1-disubstituted styrene using Ni-catalysis. Employing an air-stable Ni(II) precatalyst and a commercially available chiral ligand ((S)-tBuPHOX), enantioenriched 3,3-disubstituted iodooxindoles were obtained in up to 90% yield and up to 97:3 e.r. This methodology was applied to the total synthesis of (−)-esermethole and (−)-phenserine.

Recent Strategies for Carbon−Halogen Bond Formation Using Nickel

“…(Scheme 23). [71] Highly enantioenriched iodo-oxindoles were previously unattainable,asthe asymmetric palladium variants were limited to iodo-indolines,d ihydrobenzofurans,a nd indanones. [72,73] This methodology was applied to the total synthesis of (À)-phenserine,aswell as the formal synthesis of (À)-physostigmine.T he mechanism is generally believed to initiate via an oxidative addition to the carbamoyl chloride, followed by an asymmetric migratory insertion and reductive elimination of the C À Ib ond.…”

“…(Scheme 23). [71] Highly enantioenriched iodo‐oxindoles were previously unattainable, as the asymmetric palladium variants were limited to iodo‐indolines, dihydrobenzofurans, and indanones [72, 73] . This methodology was applied to the total synthesis of (−)‐phenserine, as well as the formal synthesis of (−)‐physostigmine.…”

Recent Strategies for Carbon−Halogen Bond Formation Using Nickel

“…(Scheme 23). [71] Highly enantioenriched iodo-oxindoles were previously unattainable, as the asymmetric palladium variants were limited to iodo-indolines, dihydrobenzofurans, and indanones. [72,73] This methodology was applied to the total synthesis of (À)-phenserine, as well as the formal synthesis of (À)-physostigmine.…”

Reversible C–C Bond Formation Using Palladium Catalysis

“…This cycloisomerization reaction proved to be quite general as both the palladium-and nickel-catalyzed carboiodination provided access to a variety of structurally diverse compounds. 32,33,[42][43][44][34][35][36][37][38][39][40][41] In particular, in 2014 we reported the palladium-catalyzed carboiodination reaction to generate syn iodo-dihydroisoquinolones 37 and in 2019 reported the nickel catalyzed variant which gave access to the corresponding anti-iodo-dihydroisoquinolones. 41 With access to both the anti-and syn-diastereomers of the iodinated compounds, we had an ideal opportunity to investigate the reversibility of the carbohalogenation process.…”