A Facile Synthesis of the Basic Steroidal Skeleton Using a Pauson−Khand Reaction as a Key Step

Abstract

A high-yield synthesis of steroid-type molecules under mild reaction conditions is achieved in two steps involving nucleophilic addition of alkynyl cerium reagent to an easily enolizable carbonyl compound (beta-tetralone) followed by an intramolecular Pauson-Khand reaction.

Synthesis of 1,8,9,16-Tetrakis(trimethylsilyl)tetra-cata-tetrabenzoquadrannulene

“…Organocerium reagents are known to enhance nucleophilicity and decrease the basicity of organolithium and Grignard reagents . The organocerium reagents promote 1,2-addition to carbonyls and suppress enolization in many reactions. − This methodology worked, providing the tetraols 7 …”

Transition‐Metal‐Mediated or ‐Catalyzed Syntheses of Steroids and Steroid‐Like Compounds

“…One such example is a synthesis of estrone-like compounds with modified D rings by Chung et al [21] The synthesis of the enynes 4 (Scheme 3), which were prepared from the commercially available β-tetralone, yielded suitable precursors for the Pauson-Khand reaction. The Pauson-Khand reaction was also used for modification of the steroid D ring.…”

Synthesis of an (±)‐Estrone Precursor: The Scope of Zr‐ and Co‐Mediated Cycloannulations

“…The best results were obtained with the classical procedure (method A), relying on the use of a stoichiometric amount of Co 2 (CO) 8 , followed by decomplexation of the formed complex with DMSO instead of N-methylmorpholine N-oxide (NMO). [33] Under these conditions, the corresponding estratetraenes 11a, 11b, 11d-f were isolated in high yields (84-95 %; Table 1, Entries 1, 2, 4-6). Only in the case of enyne 5c did cyclocarbonylation afford the corresponding product 11c in mediocre 41 % isolated yield.…”

“…[31] Interestingly, despite its synthetic scope it has found just one application in the synthesis of steroids: [32] cyclocarbonylation of steroidal enynes having different spatial arrangement of the double and triple bonds in comparison with 5b. [33] The Pauson-Khand reaction of prepared enynes 5 was studied under various reaction conditions ( Table 1). The best results were obtained with the classical procedure (method A), relying on the use of a stoichiometric amount of Co 2 (CO) 8 , followed by decomplexation of the formed complex with DMSO instead of N-methylmorpholine N-oxide (NMO).…”