Cyclopropyl ring-opening

The most frequently encountered examples of cyclopropyl ring opening reactions in the steroid field are usually associated with angular or side chain methylation sequences. In fact, isotope labeling of the C-19 angular methyl group is the only reported application of this reaction for deuteration or tritiation pui poses. 

Deuteration by cyclopropyl ring opening Ijas been used also for the stmcture elucidation of a photolysis product (241) of cholesta-3,5-diene. This bicyclobutyl derivative is very reactive and readily hydrolyzed by aqueous dioxane. When the ring opening is carried out in the presence of deuterium oxide, a deuterium is incorporated in the 4y -position of the resulting 6jS-hydroxy-3a,5a-cyclocholestane (242). ... 

Addition of PhPdl to the allene triggers cyclopropyl ring opening to generate a cr-palladium species, which readily leads to a 1,3,5-triene through /3-elimination. From the observed diastereoselectivities, the reaction seemingly proceeds stepwise via the well-stabilized zwitterionic intermediate. 

On the other hand, a recent crystallographic study revealed that the trans-2-phenylcyclopropylamine (8a) forms a cyclopropyl ring-opened adduct with MAO B at the flavin C(4a), and no evidence was obtained for inhibitor binding at Cys-365 [70,127]. From this observation, Edmondson and coworkers suggested [70] that the inhibition mechanism might be accommodated by a mechanism similar to that proposed by Sayre et al. for the quinone-mediated oxidative cleavage of cyclopropylamines [128]. 

Cyclopropyl groups have been used to probe for ketyl anion intermediacy in reactions of Sml2 with ketones. In 1991, Molander reported that treatment of cyclopropyl ketone 15 with Sml2 yields ring-opened product 16 in 81% overall yield (equation 10)56 Timberlake and Chen reported that several cyclopropyl-ring-opened products result from treatment of 17 with Sml2 (Scheme 17)57. 

The tandem cyclopropyl ring-opening/nitrilium ring-closing reaction in the presence of triflic acid results in the stereoselective formation of cyclic imines 161 (Scheme 5.67).699... 

Cyclopropyl ketones (19, R1 = Me, Et, cyclopentyl) have been converted to enamines (20 R2N = Me2N, Et2N, pyrrolidino, morpholino), but when R = aryl or cyclopropyl, ring opening occurs153. 

A well designed simple cyclopropyl ring opening is a key step of a new total synthesis of ( )-estrone by Pattenden (Scheme 22). An initial 2-endo-trig macrocyclization was followed by the ring opening. Two additional cy-clizations stereoselectively assembled the estrone skeleton 66, albeit in low yield [81]. 

Cyclopropyl ring opening at the C3 —C4 carbon bond results in the formation of a primary carbenium ion ... 

The presence of an aromatic substituent is not a necessary condition for cyclopropyl ring-opening. Such a process was found to take place also in the anodic oxidation of alkyl substituted cyclopropanes (cf. entries b) and (c) in Table 12). It is noteworthy that the structures or distributions of the products obtained from the anodic oxidation of... 

The cis-enriched fraction was purified in 5 g batches by ion exchange chromatography on Dowex 50-X8 resin with 1.5 N hydrochloric acid as eluent. Under these conditions, the cis-isomer eluted first (11). Both amino acids 15 and 16. were obtained as analytically pure, crystalline hydrochlorides upon evaporation of the acid eluates. No evidence ( H NMR) of any cyclopropyl ring opening was noted. 

In contrast to the formation of covalent adducts at flavin or at an amino acid residue by A -cyclopropyl-Af-arylalkylamines and 2-phenylcyclopropylamine, respectively, inactivation of MAO by 1-phenylcyclopropylamine leads to both types of adducts 100). Both inactivation pathways are proposed to originate from an initial one-electron oxidation by flavin to produce a common intermediate, the amine radical cation 33 in Scheme 22 (compounds 33-39). Homolytic cyclopropyl ring opening would lead to the reactive primary alkyl radical 34, which could be captured by the active site radical, either flavin semiquinone or amino acid centered. Subsequent hydrolysis of the imine, pathway (a), forms a... 

Silverman and Zieske have rationalized how a protein nucleophile other than flavin is involved in MAO inactivation reactions, and why different inactivator compounds specifically react with flavin, protein amino acids, or both (100). Hydrogen atom donation from a cysteine residue to the flavin semiquinone radical would produce a thiyl radical, which could then capture the primary or secondary alkyl radical generated on cyclopropyl ring opening from the amine radical cation of the inactivator. The hydrogen atom abstraction reaction between the flavin and active site amino acid may be an equilibrium process such that either species could be present at any turnover. Hence, a combination of steric constraints and proximity to either the flavin semiquinone radical or the thiol radical will determine the site of adduct formation for a particular inactivator structure. A two-dimensional representation is shown in Scheme 23 (compounds 40-42), which illustrates the proposed equilibrium between the flavin semiquinone radical and amino acid as well as the proposed intermediates for the inactivation of MAO by A-(l-methylcyclopropyl)benzylamine 40 (104), rrradical center relative to the particular protein radical is consistent with proposed site of attachment of inactivator to protein 40 is near the flavin radical, such that exclusive flavin attachment occurs, 41 is positioned closer to the amino... 

Scheme 12. Examples of cyclopropyl ring opening by TMM diyls...

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