Synthesis of Angularly Fused Carbocycles via Tandem Radical Cyclization of α‐Carbonyl Radicals

Abstract

An α-carbonyl radical cyclization approach towards the synthesis of angularly fused tricyclic systems is described. On reduction with tributyltin hydride, bromo ketones yield a α-carbonyl radical that undergoes successive 5-exo-dig/trig cyclizations, resulting in two or four contiguous stereocenters.

Polyaromatic Ribbons from Oligo-Alkynes via Selective Radical Cascade: Stitching Aromatic Rings with Polyacetylene Bridges

“…As expected from general trends in alkyne cyclizations, , both intramolecular radical attacks at the triple bonds proceed via an exoclosure leading to the selective formation of substituted 1-benzylidene-2-phenyl-3,4-dihydro-1H-5-oxa-acenaphthylenes 2 . Literature examples of two consecutive ring closures in bis-TMS-acetylenes are scarce. The 87% yield for the cyclization of bis-TMS-enediyne 2e is a particularly convincing illustration for the efficiency of this radical cascade.…”

Cyclizations of Alkynes: Revisiting Baldwin’s Rules for Ring Closure

“…Medium-sized groups ( i -Pr and n -Pr) gave mixtures with the 5-exo/6-endo ratio correlating with the steric bulk of the substituents (∼2:1 and ∼5:4, respectively, Scheme ) . Carbamoylmethyl radicals, (both C-allylendo2 and C-allylexo, Scheme ) also undergo selective 5-exo-dig cyclizations with terminal and TMS-substituted alkynes, respectively.…”

The Wieland-Miescher Ketone: A Journey from Organocatalysis to Natural Product Synthesis

“…At the beginning of the project very little literature on the enantioselective preparation of C-8a Wieland-Miescher ketone analogues was available, 54 and consequently, there had been little utilization of these types of compounds in total synthesis. 55 Key to accessing these types of ana-logues is the synthesis of the corresponding 2-substituted cyclohexane-1,3-dione starting materials for which there are three main approaches (Scheme 5): (a) direct alkylation of cyclohexane-1,3-dione (33) with activated alkyl groups (such as methyl or allyl halides) using bases such as KOH 56 or Triton B; 57 (b) coupling of cyclohexane-1,3dione (33) with an aldehyde followed by trapping with thiols 58 or pyrrolidines, 59 or reduction with the Hantzsch ester; 54e or (c) alkylation of the dimethoxy compound 34 with unactivated alkyl halides utilizing t-BuLi in HMPA. 60 Scheme 5 Methods for the preparation of 1,3-diketone starting materials When deciding which substituent to introduce, we reflected on our model work 61 in which stepwise elaboration of an abridged side chain had proved lengthy and problematic.…”