Roger C. Hahn

One-pot, one- and multi-carbon homologation of alkyl halides; reaction of Grignard reagents with chloroiodomethane

Abstract Reaction of a Grignard reagent (RMgX) with chloroiodomethane affords the corresponding iodide (RI) and, depending on R, solvent, and temperature, iodides which are one-carbon and multicarbon homologs of RX. Allyl iodide but not allyl bromide can be monohomologated by the combined action of chloroiodomethane and isopropyl Grignard.

(7R,8S)-cis-7,8-EPOXY-2-METHYLOCTADEC-17-ENE: A NOVEL TRACE COMPONENT FROM THE SEX PHEROMONE GLAND OF GYPSY MOTH, Lymantria dispar

Considering the vast Eurasian distribution of gypsy moth, Lymantria dispar (Lepidoptera: Lymantriidae), the many subspecies, and their presence in different lymantriid communities, we tested the hypothesis that L. dispar populations in eastern Asia employ one or more pheromone components in addition to the previously known single component pheromone (7R,8S)-cis-7,8-epoxy-2-methyloctadecane [= (+)-disparlure]. Coupled gas chromatographic–electroantennographic detection (GC–EAD) analyses of pheromone gland extracts of female L. dispar sensu lato (including both AGM and NAGM) on four GC columns (DB-5, DB-23, DB-210, and SP-1000) revealed a new trace component that eluted just before (DB-5; DB-210) or after (DB-23, SP-1000) disparlure, and elicited strong antennal responses. Isolation of this compound by high-performance liquid chromatography and hydrogenation produced disparlure, suggesting that the new component had the molecular skeleton of disparlure, with one or more double bonds. Of all possible monounsaturated cis-7,8-epoxy-2-methyloctadecenes, only cis-7,8-epoxy-2-methyloctadec-17-ene co-chro- matographed with the insect-produced compound on all GC columns and elicited comparable antennal responses. In field experiments in Honshu (Japan) with enantioselectively synthesized compounds, (7R,8S)-cis-7,8-epoxy-2- methyloctadec-17-ene (7R8S-epo-2me-17-ene-18Hy) was weakly attractive to male L. dispar, but was less effective as a trap bait than (+)-disparlure, and failed to enhance attractiveness of (+)-disparlure when tested in blends. The antipode, (7S,8R)-cis-7,8-epoxy-2-methyloctadec-17-ene, was not attractive, and when added to (+)-disparlure and/or 7R8S-epo-2me-17-ene-18Hy reduced attractiveness. Thus, the biological role of 7R8S-epo-2me-17-ene-18Hy remains unclear. It may enhance pheromone attractiveness or specificity in other L. dispar populations within their vast Eurasian distribution.

Sex Pheromone Components of Casuarina Moth, Lymantria xylina

Abstractcis-7,8-Epoxy-2-methyleicosane is a sex pheromone component of the Casuarina moth, Lymantria xylina Swinhoe. The compound was extracted from pheromone glands of female moths and was identified by coupled gas chromatographic–electroantennographic detection (GC-EAD) and GC–mass spectrometry. In field experiments in Taiwan, traps baited with either or both of (7R,8S)-cis-7,8-epoxy-2-methyleicosane (>99% ee) [termed here (+)-xylinalure] and (7S,8R)-cis-7,8-epoxy-2-methyleicosane (>99% ee) [termed here (−)-xylinalure] captured male L. xylina. Addition of further candidate pheromone components to xylinalure did not enhance its attractiveness. Demonstration of whether or not female L. xylina produce both optical isomers of xylinalure, and determination of the ratio, will require pheromone extract analyses on a chiral, enantiomer-separating column (as yet unavailable) or derivatization of epoxides in accumulated gland extracts. Attraction of male L. xylina to either enantiomer of xylinalure contrasts with enantiospecific production of, and/or response to, epoxy pheromones in congeners. With no other nocturnal lymantriid moth known in Taiwan to utilize xylinalure for pheromonal communication, enantiospecific “fine tuning” of xylinalure, or evolution of a more complex pheromone blend, may not have been necessary for L. xylina to maintain specificity of sexual communication. Racemic xylinalure will be appropriate for pheromone-based detection surveys of L. xylina in North America.

A Scalable, Nonenzymatic Synthesis of Highly Stereopure Difunctional C4 Secondary Methyl Linchpin Synthons

In response to the continuing widespread use of heterodifunctional C4 secondary methyl building blocks in asymmetric synthesis, we have developed a mole-scale, two-step synthesis of a 1:1 mixture of the diastereomers of 3-bromo-2-methyl-1-propyl camphorsulfonate (casylate). One isomer (2S) has been crystallized to >99:1 dr in ∼25% yield. Equilibration of the mother liquor (enriched in 2R) to a 1:1 mixture and recrystallization significantly raises the overall yield of 2S. Applications of 2S include chemoselective Grignard coupling, enabling the very short synthesis of highly stereopure long-chain natural products containing remote, methyl-bearing stereogenic centers [e.g., (R)-tuberculostearic acid], with complete control of configuration. Also, Ag-mediated, completely chemoselective Br displacement from 2S leads to a range of >99:1 er difunctional synthons. Both applications incorporate concurrent recovery of CasO. The enantiomer of 2S can be made from commercial (1R)-10-CasOH.

Sex Pheromone Components of Indian Gypsy Moth, Lymantria obfuscata

The Indian gypsy moth, Lymantria obfuscata (Lepidoptera: Lymantriidae), has been recognized as a distinct species since 1865 but closely resembles a diminutive form of gypsy moth, Lymantria dispar. We tested the hypothesis that the sex pheromones of L. obfuscata and L. dispar are similar. In laboratory mate acceptance studies, very few male L. dispar made copulatory attempts when paired with female L. obfuscata, suggesting that female L. obfuscata emit one or more pheromone components antagonistic to male L. dispar. In coupled gas chromatographic–electroantennographic detection (GC–EAD) analyses of pheromone gland extract of female L. obfuscata, (Z)-2-methyloctadec-7-ene (2Me-7Z-18Hy) and (7R,8S)-cis-7,8-epoxy-2-methyloctadecane [(+)-disparlure] were most abundant and elicited the strongest responses from male L. obfuscata antennae. In field experiments near Solan (Himachal Pradesh, India), 2Me-7Z-18Hy and (+)-disparlure in combination attracted more male L. obfuscata than did either component alone. This two-component sex pheromone contrasts with the single-component sex pheromone [(+)-disparlure] of L. dispar. The contrasting composition of the lymantriid communities inhabited by L. obfuscata and L. dispar may explain why 2Me-7Z-18Hy is a pheromone component in L. obfuscata and a pheromone antagonist in L. dispar and why (−)-disparlure reduces pheromonal attraction of male L. dispar but not male L. obfuscata.