Free radical cyclizations in alkaloid synthesis: (+)-heliotridine and (+)-hastanecine

Thiols, thioethers, and related compounds as sources of C-centred radicals

“…In all cases, non-cyclized desulfurization products are isolated, even under high dilution of tin hydride (Scheme 88, eqn (b)). 202,203 Interestingly, 6-exo cyclizations are more efficient (Scheme 88, eqn (c)). Padwa showed that N-benzyl and N-sulfonyl analogues fail to cyclize in a 5-exo-trig mode and gave only moderate yields in 6-exo-trig cyclizations.…”

Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

“…The high stereoselectivity of the ring-formation step can be explained by the suprafacial addition of the allene to the double bond of the α,β-unsaturated compound 4 , the diastereoselectivity being sterically controlled by the methyl group on the β-face. The transformation of the vinylsilane moiety in 5 into the corresponding carbonyl group ( Scheme 4 ) was carried out by a two-step procedure involving epoxidation of the vinylsilane 5 , followed by a rearrangement of the diastereomeric mixture of epoxides 7 induced by formic acid [ 34 – 35 ]. The resulting ketone 8 was obtained as a 3.5:1 mixture of epimers at C3.…”

Pyrrolizidine alkaloids

“…A different radical-initiated cyclization procedure has been used by Choi and Hart to produce (+)-heliotridine (18) and (+)-hastanecine (20) from (9-malic acid (Scheme 8). 13 The carbinolamide (36) was the major product when the corresponding imide was regioselectively reduced. Acetylation of the silane (36) and replacement of the acetyl group gave the phenylthio-compound (37 ; R = SPh).…”