Stereochemistry of the reaction of cyclopropanes with mercuric trifluoroacetate

Abstract

The various stereoisomers of 1,2,3-trimethyl-1 -phenylcyclopropane, 2,3-dimethyl-l-phenylcyclopropane, and 2,3-dimethylcyclopropanol methyl ether have been reacted with mercuric trifluoroacetate in methanol and the stereochemistry of both electrophilic and nucleophilic attack has been determined. The electrophilic mercury reacts at the least substituted ring bond (for bonds of equal substitution attack at a cis-substituted bond is preferred over attack at a trans-substituted one). Ring opening occurs in the direction of the more stable carbonium ion, which can lead to either retention or inversion at the site of electrophilic substitution. The opening occurs with substantially complete inversion of configuration at the site of nucleophilic attack. If all ring bonds are identically substituted, as is c«-l,2,3-trimethylcyclopropane, the ring-opened product arises from 62% inversion and 38% retention of configuration at the site of mercury attack and 100% inversion by the methanol. The results seem best to be accounted for by the formation, in the rate-determining step, of a corner-mercurated cyclopropane which ring opens by nucleophilic substitution by solvent.

Synthesis and stereochemistry of 23,24-dihydrocalysterol: implications for marine sterols of a unified biosynthetic scheme involving protonated cyclopropanes

“…Cleavage of the C(23)-C(24) bond with concomitant bond formation between C-24 and C-27 as depicted gives rise to the protonated petrosterol species (7a),(7b), which can lose a proton to give petrosterol (7) or undergo further isomerization, as shown, to the dehydroaplysterol derivative (21), viu (21a),(21b). First, 24-methylenecholesterol (2), rather than epicodisterol (24), codisterol (25), or the diene (26), should be the immediate biosynthetic precursor of (7) (Scheme 4).24 Second, this mechanism predicts an extensive and specific rearrangement of the cholesterol side-chain carbon atoms [note side-chain carbon numbering in (7), Scheme 41-a prediction which is testable by the feeding of specifically labelled precursors.c Scheme 5 depicts our proposed biosynthesis of ficisterol (22) l 7 and the recently isolated hebesterol (23).' First, 24-methylenecholesterol (2), rather than epicodisterol (24), codisterol (25), or the diene (26), should be the immediate biosynthetic precursor of (7) (Scheme 4).24 Second, this mechanism predicts an extensive and specific rearrangement of the cholesterol side-chain carbon atoms [note side-chain carbon numbering in (7), Scheme 41-a prediction which is testable by the feeding of specifically labelled precursors.c Scheme 5 depicts our proposed biosynthesis of ficisterol (22) l 7 and the recently isolated hebesterol (23).'…”

“…Scheme 3 has several implications in regard to petrosterol biosynthesis. First, 24-methylenecholesterol (2), rather than epicodisterol (24), codisterol (25), or the diene (26), should be the immediate biosynthetic precursor of (7) (Scheme 4).24 Second, this mechanism predicts an extensive and specific rearrangement of the cholesterol side-chain carbon atoms [note side-chain carbon numbering in (7), Scheme 41-a prediction which is testable by the feeding of specifically labelled precursors.c Scheme 5 depicts our proposed biosynthesis of ficisterol (22) l 7 and the recently isolated hebesterol (23).' Ob It follows a course similar to that of Scheme 3 except that, now, the proton labilizes the C(24)-C(28) bond and nucleophilic attack occurs from C-26 [see (%),@I) Scheme 51.…”

“…The choice of (11) over (IIa) and (IIb) as the reacting conformer was made on the basis of its being the conformer of lowest potential energy. While we recognized that this conformation might not have been that existing at the enzyme active site we were gratified that it indeed provided the basis for interrelating the structures and absolute stereochemistries of the sterols (l), ( 7), ( 8), (21), (22), and (23). It should be noted that invoking conformer (Ha) in Scheme 3 or conformer (IIb) in Scheme 5 would result in cyclopropanes having a cis substituted ring system.…”

“…While we recognized that this conformation might not have been that existing at the enzyme active site we were gratified that it indeed provided the basis for interrelating the structures and absolute stereochemistries of the sterols (l), (7), (8), (21), (22), and (23). While we recognized that this conformation might not have been that existing at the enzyme active site we were gratified that it indeed provided the basis for interrelating the structures and absolute stereochemistries of the sterols (l), (7), (8), (21), (22), and (23).…”

“…of dihydrocalysterol(1) with petrosterol(7), ' 26-dehydroaplysterol (21),16 and ficisterol (22) l 7 in P.Jiciforrnis; with nicasterol (8) in C. niceuensis; and with hebesterol (23) l o b in P. hebes; and the question as to whether there is a biosynthetic relationship among these unusual sterols. Since dihydrocalystersl (1) is a common denominator, our analysis started with this sterol.…”