Benzyne Insertion onto β-Keto Esters of Polycyclic Natural Products: Synthesis of Benzo Octacyclo Scaffolds

Abstract

Benzyne insertion to build the privileged scaffold of a [6.8.6]-tricyclic framework on polycyclic and sp 3 -rich natural products has been developed. The formation of the [6.8.6]-tricyclic ring system is solvent dependent.

sp3‐Rich Glycyrrhetinic Acid Analogues Using Late‐Stage Functionalization as Potential Breast Tumor Regressing Agents

“…C‐arylation and ring‐expansion studies : We have earlier extended the A‐ring of 1 by aryne insertion and thereby creating new skeletons . In this process, 8 new analogues, wherein the late stage arylation/A‐ring expansion was achieved to build the diversity around A‐ring of 1 (Scheme ).…”

“…We have earlier extended the A-ring of 1 by aryne insertion and thereby creating new skeletons. [17] In this process, 8 new analogues, wherein the late stage arylation/A-ring expansion was achieved to build the diversity around A-ring of 1 (Scheme 1). Molecule 1 was modified to get the required β-keto ester which allowed a solvent-dependent C-arylation or A-ring expansion.…”

Advances in the Semi-Synthesis of Triterpenoids

“…41 Scheme 17 Synthesis of 97 via BAR In addition, benzyne species could trigger the rearrangement of A-ring of GA derivatives, providing triterpenoids with expanded A-ring fused to an extra phenyl ring (Scheme 18). 42 GA was subjected to Jones oxidation and methyl esterification to provide 98 (85%, 2 steps), which was then exposed to C2methoxycarbonyl group incorporation with dimethyl carbonate to give 99 (75%). With 99 in hand, the conditions for the desired benzyne-initiated A-ring rearrangement was carefully optimized, and were finally fixed as CsF in THF media at 80 o C. Under these conditions, the GA-derivative 100 with an expanded and phenyl ring-fused A-ring was obtained regioselectively and stereoselectively (45%).…”

“…In addition, benzyne species can trigger rearrangement of the A ring of glycyrrhetinic acid (GA) derivatives, providing triterpenoids with an expanded A ring fused to an additional phenyl ring (Scheme 18). 42 GA was subjected to Jones oxidation and methyl esterification to provide 98 (85%, 2 steps), which was then exposed to C2-methoxycarbonyl group incorporation with dimethyl carbonate to give 99 (75%). With 99 in hand, the conditions for the desired benzyne-initiated A-ring rearrangement were carefully optimized, and were finally fixed as CsF in THF at 80 °C.…”

Cascade aryne insertion/vinylogous aldol reaction of vinyl-substituted β-keto/enol carbonyls

“…With this assumption, cycloheptenone 5 15 was subjected to carbomethoxylation with NaH as a base, and dimethyl carbonate ( 6 ) as an electrophile in anticipation of the formation of 4 . 16 With 1 H NMR and mass spectroscopic analysis revealing the introduction of a –CO 2 Me group, the Stoltz protocol was initiated with aryne 3a in the presence of CsF. Disappointingly, the desired tricyclic intermediate 2 was not observed.…”