Highly functionalized donor–acceptor cyclopropanes applied toward the synthesis of the Melodinus alkaloids

Abstract

A series of highly substituted vinylcyclopropanes were prepared and examined as reaction partners in a palladium-catalyzed (3 + 2) cycloaddition with nitrostyrenes. Described herein are our efforts to synthesize an elusive 1,1-divinylcyclopropane by several distinct approaches, and to apply surrogates of this fragment toward the synthesis of the Melodinus alkaloids.

Synthetic Strategy toward the Pentacyclic Core of Melodinus Alkaloids

“…19b To a stirred solution of aniline (27.3 g, 293.5 mmol) and ethyl glyoxalate (30 g, 293.5 mmol) in MeCN (250 mL) were added CAN (5.3 g, 14.7 mmol) and cyclopentadiene (29.1 g, 441.0 mmol) at 0 °C, and the resulting mixture was stirred at rt for 5 h. After completion of the reaction, the reaction mixture was diluted with water and extracted with CH 2 Cl 2 . The organic layer was separated and washed with brine and then dried over anhydrous Na 2 SO 4 and concentrated to get crude product, which was subjected to column chromatography on silica gel (10% EtOAc in hexane) to afford 6 (48.4 g, 68%) as a white solid: mp = 56−58 °C; Ethyl 5-Acetyl-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-4-carboxylate (10). Compound 6 (23.0 g, 94.6 mmol) was dissolved in CH 2 Cl 2 (250 mL) at room temperature under nitrogen atmosphere.…”

Diastereoselective Synthesis of Spiro and Chlorocyclopropanes from Camphorpyrazolidinone derived -Unsaturated Amides

“…The -bromo substituents 2k gives inseparable multiple products. This method is supervisor over reported method where direct substitution of halogen from gem-dihalocyclopropanes is limited 22 and dialkylation with a new 'cyclocuprate' species to yield spiro compounds is possible if the reaction is performed in the presence of a lithium acetylide 23 .…”

Synthetic Applications and Methodological Developments of Donor−Acceptor Cyclopropanes and Related Compounds

“…Unfortunately, despite significant effort, the synthesis of divinyl cyclopropane 55 proved elusive . A revised retrosynthesis was developed, beginning with a monovinyl cyclopropane in the (3+2) reaction, and relying on a late‐stage C−H vinylation to install the second vinyl group.…”

“…Unfortunately, despite significant effort, the synthesis of divinyl cyclopropane 55 proved elusive. [34] A revised retrosynthesis was developed, beginning with a monovinyl cyclopropane in the (3 + 2) reaction, and relying on a late-stage C–H vinylation to install the second vinyl group. The use of stable vinylcyclopropane 56 (Scheme 12) relied upon the known reactivity of such compounds to unveil their donor–acceptor reactivity upon treatment with palladium(0) complexes.…”