A Free-Radical and Protecting-Group-Free Approach to (–)-Boschnialactone and γ-Lycorane

Abstract

The protecting-group-free (PGF) and free-radical-based synthesis of two structurally different natural products, (–)-boschnialactone and γ-lycorane, is reported. The key step in both syntheses is a radical–ionic sequence for construction of the principal structure (a six-membered lactone and a 1,4-dicarbonyl compound, respectively), allowing short and rapid access to these natural products through a PGF route.

Hydroamination of Dihapto‐Coordinated Benzene and Diene Complexes of Tungsten: Fundamental Studies and the Synthesis of γ‐Lycorane

“…The product was purified by flash chromatography on silica gel, eluting with AcOEt, then 1 % Et 3 N in AcOEt, yielding 27 (8 mg, 0.031, 84 % yield) as an oil. Proton NMR data match those of title compound 27 [24–37] …”

“…The first asymmetric synthesis of γ‐lycorane was reported by Mori in 1995, [23] and its structure is considered prototypical for this important class of alkaloids. In just the past five years, well over a dozen new syntheses of the lycorine family have appeared [24–37] . Of these, only one uses a benzene ring as the source of the C ring, which contains all of the stereocenters.…”

Progress towards the Total Syntheses of Amaryllidaceae Alkaloids γ‐Lycorane

“…γ-Benzyloxy vinylogous A similar strategy to Tu's work was exploited by Cordero-Vargas et al that took advantage of the freeradical and protect-group-free approach to access (�)γ-lycorane (�)-6 (Scheme 19). [49] In this protocol, the synthesis commenced with the conversion of known ketone 71, which was prepared in two steps from cyclohexene oxide 96, [42] into enol acetate 97 by enolate formation with LDA and trapping with Ac 2 O. The radical addition of enol acetate 97 with iodoacetonitrile was carried out in the presence of dilauroyl peroxide (DLP) to provide keto nitrile 23 as a separable mixture of 1, 3-cis-23 (81 %, major) and 1, 3-trans-23 (3 %, minor) diastereoisomers.…”

Evolution of Strategies in Protecting‐Group‐Free Synthesis of Natural Products: A Recent Update

“…Boschnialactone ( 94 ) was isolated by Sakan and co‐workers from Boschniakia rossi ca. [ 41 ] In 2019, Cordero‐Vargas and co‐workers [ 42a ] reported a free radical and PGF‐synthesis of boschnialactone ( 94 ) and γ‐lycorane ( 101 ) in a handful of steps (Scheme 11). The synthesis started from ( R )‐citronellal ( ent ‐ 1 ), which on α‐methylenation delivered 92 .…”

“…The simple structures and not many functional groups allowed the conventional PGF synthesis of boschnialactone (5 steps) accomplished in 17.6 % overall yield and that of γ‐lycorane (6 steps) in 34 % overall yield. All the earlier asymmetric syntheses of boschnialactone ( 94 ), except that by Nangia [ 42e ] involved protecting groups and hence were less step‐economic and had lower overall yields.…”