Cyclization of vinyl radicals: a versatile method for the construction of five- and six-membered rings

Is There No End to the Total Syntheses of Strychnine? Lessons Learned in Strategy and Tactics in Total Synthesis

“…Reductive radical-chain cyclization of 61 proceeded in good yield to give a 1:1 mixture of TBS-protected isostrychnine 69 and double bond isomer 68 , with the loss of configuration of the C19–C20 double bond arising from rapid isomerization of the vinyl radical intermediate. [70c,76] Alternatively, Heck cyclization of 61 provided pyridone 70 , which could be reduced to isostrychnine derivative 69 using lithium aluminum hydride, but the overall yield of the two-step stereoselective process was lower than the yield of pure 69 obtained from radical cyclization. It is noteworthy that the LiAlH 4 reduction yielded the correct configuration at C2 without the presence of a directing group, remarkable selectivity the authors attributed to hydride attack from the less-hindered Si face of the pyridone.…”

Synthetic Strategies Directed Towards 5a‐Carbahexopyranoses and Derivatives Based on 6‐endo‐trig Radical Cyclizations

“…On the other hand, it was intended to generate the vinyl radical by tributyltin hydride addition to a terminal alkyne (Scheme 2, R = SnBu 3 ). [22] The enynes 20a and 20b, based on d-glucose and d-galactose diacetonides, were chosen as our test candidates, and their preparation is outlined in Scheme 3. The synthesis of the alkynes 17a and 17b was carried out by the procedure of Toma and co-workers, [23] though with some modifications.…”

Radical Reactions

“…One of the earliest examples of vinyl radical cyclization to generate a quaternary center was reported by Stork and coworkers [8]. Under standard photolytic conditions, using tributylstannane and azobis(isobutyronitrile) (AIBN), the achiral cyclohexenol substrate 1 was transformed to cis product 2 by 5-exo-trig cyclization (Scheme 11.1).…”