Preparation of Conformationally Constrained α₂‐Antagonists: The Bicyclo[3.2.0]heptane Approach

Abstract

The aim of this research was to discover α 2 -receptor antagonist subtypes that are more selective than known compounds. We focused on rigid molecules possessing a benzofused bicyclo[3.2.0]heptane skeleton. The synthetic route used relied upon the intramolecular [2+2] cycloaddition of styrylketene precursors. The cycloaddition was remarkably efficient and delivered multigram quantities of the cycloadduct 2. Studies of the removal of the ketone group in 2 revealed a facile opening of the four-membered ring. Upon thermal elimination of TCI-13-endo (TCI = thiocarbonylimidazole) and TCI-13-exo, different products were obtained depending on the stereochemistry of the OH function of the precursor. Distinct mechanisms were proposed to account for

Total Synthesis of Debromoflustramines B and E Based on the Intramolecular Carbamoylketene–Alkene [2 + 2] Cycloaddition

“…To improve the yield of 23d , treatment of a mixture of the carboxylic acids with ethyl chloroformate and triethylamine in THF at room temperature produced cleanly a separable mixture of 23d and the cyclized product 24d in 60% and 2% yield, respectively (entry 5). Thus, we were able to develop an alternative and mild procedure (condition B) for the generation of the carbamoylketene (Table ).…”

Synthetic Studies on Cyclobuta[a]indanes: Stereocontrolled Access to C9-Substituted Derivatives

“…This transformation was best achieved by masking first the ketone as its Li-enolate then reducing the ester group with LAH . Although the yield of 9 was modest (50%), this variant represents a substantial improvement over our previous work, avoiding the need for tedious oxidation level adjustments at C9 and protection−deprotection at C11. Reaction of 9 with dimethylallylchlorosilane followed by Wittig methylenation of the resulting ether ( 10 ) provided the RCM precursor 8 .…”

“…The most straightforward preparation of compound 5 involves hydrogenation of substrate 3 or 6 (Scheme ). Both were assembled from the known cyclobutanone 1 . Thus, compound 1 was converted to the ethyl cyclobutene derivative 3 through a Negishi-type coupling between the enol triflate 2 and diethylzinc.…”

“…Before our work, polycyclic systems of this type had been rarely documented in the literature . Herein, we present the progress made toward the construction of the model compound 5 using different, complementary routes.…”

Thiocarbonyl Ylide Chemistry Enables a Concise Synthesis of (±)-Hippolachnin A

“…12 from the convex side to 10, followed by Wittig olefination 13 and hydrolysis of the enol ether, 14 gave rise to ketone 14 as a 10:1 mixture of Z-and Eisomers (major isomer shown). Homologation of ketone 14 was then achieved by formation of the vinyl triflate 15 and subsequent carbomethoxylation. 16 The stage was now set for the introduction of the two remaining ethyl groups.…”