Asymmetric induction in the ene reaction of glyoxylate esters of 8-phenylmenthol

Synthesis of (+)-9-Demethyl-7,8-dideoxycalopin as a Model for the Determination of the Absolute Stereochemistry of a New Group of Fungal Metabolites

“…The observed selectivity is explained by a transition state in which the aromatic residue adopts an equatorial orientation, as described before. [3] The absolute configuration of 9 was confirmed as (2S,3R) by a single-crystal X-ray diffraction analysis ( Figure 1). Scheme 2.…”

“…The latter compound should be available by means of an enantio-and diastereoselective glyoxylate-ene reaction between compounds 6 and 7. [2,3] Scheme 1. Retrosynthetic analysis of model compound 3…”

“…The glyoxylate-ene reaction developed by Whitesell et al [2,3] would fulfill these requirements, although there has been no reported application to β,β-disubstituted styrenes. In the event, phenylmenthyl glyoxylate 8 [2,3] reacted with β,β-dimethylstyrene (7) in the presence of SnCl 4 to yield the desired α-hydroxy ester 9 as the only detectable diastereomer (as judged by GC/MS), in 81% yield (Scheme 2). The observed selectivity is explained by a transition state in which the aromatic residue adopts an equatorial orientation, as described before.…”

“…[12,13] Independent evidence for the same absolute configuration of synthetic (ϩ)-9-demethyl-7,8-dideoxycalopin (3) and (ϩ)-calopin (1b) was obtained from the similarity of the CD spectra of both compounds ( Figure 3). (؊)-8-Phenylmenthyl (2S,3R)-2-Hydroxy-4-methyl-3-phenylpent-4-enoate (9): SnCl 4 (1.64 mL, 13.93 mmol) was added to a solution of freshly prepared glyoxylate 8 [2,3] (prepared by ozonolysis of 4.65 mmol of the corresponding acrylate) and β,β-dimethylstyrene (7, 685 µL, 4.66 mmol) in dry CH 2 Cl 2 (45 mL), maintained at Ϫ78°C…”

“…[1] However, their absolute configurations could not be determined unambiguously. To solve this problem we carried out an asymmetric synthesis of the calopin analogue (2S,3R,4S)-9-demethyl-7,8-dideoxycalopin (3) and then compared the 1 H NMR properties of the corresponding Mosher esters. …”