Synthesis of α‐Chlorolactams by Cyanoborohydride‐Mediated Radical Cyclization of Trichloroacetamides

Abstract

A cyanoborohydride-promoted radical cyclization methodology has been developed to access α-chlorolactams in a simple and efficient way using NaBH CN and trichloroacetamides easily available from allylic and homoallylic secondary amines. This methodology allowed the synthesis of a library of α-chlorolactams (mono- and bicyclic), which were tested for herbicidal activity, trans-3-chloro-4-methyl-1-(3-trifluoromethyl)phenyl-2-pyrrolidinone being the most active.

Boryl Radicals Enabled a Three-Step Sequence to Assemble All-Carbon Quaternary Centers from Activated Trichloromethyl Groups

“…Indeed, treatment of 2a with boryl radical precursors 1 in the presence of a radical initiator led to the sole formation of 3a in good yields, and the further reduction of 3a to form 4a was observed only to a slight extent (Table S1, entries 1−7). It should be noted that the reduction reactions of 2a using Bu 3 SnH, 56 (Me 3 Si) 3 SiH, 57 or NaBH 3 CN 58 as promoters led to a mixture of 3a and 4a with inferior selectivity (Table S1, entries 8−11). In addition, the quenching of boryl radicals I-IV by 4a was not detectable at 25 °C, indicating the lower reactivity of this monochloride.…”

Synthesis of Azabicyclic Building Blocks for Daphniphyllum Alkaloid Intermediates Featuring N‐Trichloroacetyl Enamide 5‐endo‐trig Radical Cyclizations

“…This may have been generated by a cyclization upon the isomerized trisubstituted enamide (not shown) coming from a thermal isomerization of tetrasubstituted enamide 2c , followed by reduction of a dichlorolactam intermediate, and further oxidation by the initiator AIBN . Radical cyclization of 2c was also carried out under conditions we recently reported involving NaCNBH 3 and AIBN in acetonitrile. Again, the isolated azabicyclic compound 3cb (25 %) came from an initial isomerization, but here the α ‐carbamoyl radical would have been intercepted by AIBN incorporating the 2‐cyano‐2‐propyl moiety in 3cb .…”