Studies on the Diastereoselective Preparation of Bis-cyclopropanes

Abstract

The identification of two natural products, FR-900848 and U-106305, has stimulated interest concerning the relationship between configurational isomerism, conformational isomerism, and biological activity of polycyclopropanes. Efforts to investigate the relationship between configurational and conformational isomerism through molecular modeling suggest that significantly different three-dimensional structures will result from unique primary structures. Any effort to address these issues demands that stereoselective methods for the preparation of polycyclopropanes be developed. We have investigated the application of zinc-carbenoid cyclopropanation in the presence of chiral dioxaboralanes to the preparation of eight stereochemically unique bicyclopropanes. The trans-vinylcyclopropane starting materials demonstrated very little substrate-induced stereoselectivity, while the cis-vinylcyclopropane demonstrates modest to excellent stereocontrol. A model for the substrate-based stereocontrol is proposed. We also used the spectroscopic data gathered in this investigation to probe the substrate-mediated stereocontrol in the rhodium(II)-catalyzed cyclopropanation of vinylcyclopropanes with ethyl diazoacetate.

Determination of the rate constant for ring opening of an α-cyclopropylvinyl radical

“…The alkene was identified by co-injection with an authentic sample prepared by a Wittig reaction of the corresponding aldehyde. 11 No evidence for the formation of the regioisomeric allene, 4phenylpenta-1,2-diene, was found.…”

“…No evidence for the formation of cis-2-phenylcyclopropylethene was observed during the course of these studies as noted by the comparison of GC retention times with an authentic sample. 11 The reversibility of the ring opening rearrangement of 4 to 6 does not affect the rate constant of the forward reaction. The rate constant of the reverse reaction was estimated to be 1.6 × 10 4 s −1 .…”

“…Cyclohexane was distilled from LiAlH 4 , and then purged with Ar prior to use. Tributyltin hydride was purchased from Aldrich Chemical Co. trans-2-Phenylcyclopropylethyne 8 and trans-2-phenylcyclopropylethene 11 were prepared according to the literature procedures. A mixture of cis/trans-2phenylcyclopropylethene was prepared by initial formation of the isomeric ethyl 2-phenylcyclopropylcarboxylates by CuSO 4catalyzed cyclopropanation of styrene with ethyl diazoacetate, reduction of the esters to the alcohols using LiAlH 4 and oxidation to the aldehydes using Swern oxidation conditions.…”

Xenognosin sensing in virulence: is there a phenol receptor in Agrobacterium tumefaciens?

“…Confirmation of the absolute stereochemical assignment was obtained using both coupled oscillator analysis of the dibenzoates [44,45] of the trans-CP isomers as well as an alternate enantioselective synthesis. Charrette et al [46,47] and Theberge et al [48] have demonstrated predictable stereoselective cyclopropanation using dioxaboralane enantiomers as directing groups in the Furukawa reaction [49][50][51][52]. Cyclopropanation of the protected trans-4-benzyloxy-3-methoxy cinnamyl alcohol via this stategy indeed resulted in the efficient, enantioselective (89%-92% ee) preparation of trans-CP isomers, further establishing the absolute stereochemical assignment.…”

A DFT Study on the Mechanism of Samarium (II)-catalyzed Cyclopropanation Synthesis with α,β -unsaturated Carboxylic Acids, Alcohols and Amides

“…Since the reported use of diiodomethane and a Zn/Cu couple to react with olefins to form cyclopropane units by Simmons and Smith, the cyclopropanation reaction were catalyzed by transition metals to form active reagents similar to the SimmonsSmith reagent that can make cyclopropane-containing products from olefins with high efficiency and stereoselectivity. To our best knowledge, many transition metals such as Rh, Ru, Pd, Pt, Ni, Cu, Zn, Sm, Al and Li are found to be able to catalyze cyclopropanation via a metal-carbene complex [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. Zhao and co-workers have studied the reaction mechanism of samarium (II) carbenoid promoted cyclopropanation reaction with ethylene and the effect of THF solvent [34].…”