The geometric isomers of methyl-2,4,6-decatrienoate, including pheromones of at least two species of stink bugs

All eight geometric isomers of methyl 2,4,6-decatrienoate were synthesized from readily accessible starting materials by fully exploiting Wittig-type olefinations, and taking advantage of an easy separation of 2E and 2Z unsaturated esters. The aggregation pheromone of the brown-winged green bug, Plautia stali, methyl (E,E,Z)-2,4,6-decatrienoate (also a cross-attractant for the brown marmorated stink bug, Halyomorpha halys), was expediently produced in two easy steps from (E)-4,4-dimethoxy-2-butenal in 55% yield. The sex pheromone of the red-shouldered stink bug, Thyanta pallidovirens, methyl (E,Z,Z)-2,4,6-decatrienoate, was conveniently synthesized from 2,4-octadiyn-1-ol in 32% yield using in situ manganese dioxide oxidation-Wittig condensation in a key step.     

Expedient synthesis of bisabolenol stink bug pheromones via stereodefined cyclohex-2-enones

We recently synthesized all stereoisomers of 1,10-bisaboladien-3-ol and 10,11-epoxy-1-bisabolen-3-ol, including three stink bug pheromones, via a rhodium-catalyzed asymmetric addition of trimethylaluminum to diastereomeric mixtures of cyclohex-2-enones. However, yields of trans isomers were low, and scaling reactions using expensive catalysts were cumbersome. Now we describe a new synthesis of bisabolenol stink bug pheromones via (S)- and (R)-4-((R)-6-methylhept-5-en-2-yl)cyclohex-2-enones prepared by enantioselective Michael additions of methyl vinyl ketone to (S)- and (R)-citronellals and lithium hydroxide monohydrate-catalyzed stereoselective cyclizations of intermediate ketoaldehydes. Addition of methyllithium to these enones provided cis- and trans-1,10-bisaboladien-3-ols, which were separated by chromatography on silica and further converted to 10,11-epoxy-1-bisabolen-3-ols. Thus, we developed more convenient syntheses of pheromones of the rice stink bug, the harlequin bug, and brown marmorated stink bug.     

Synthetic studies aimed at the elucidation of the stereostructure of the aggregation pheromone, 2-methyl-6-(4′-methylenebicyclo[3.1.0]hexyl)hept-2-en-1-ol,produced by the male stink bug Erysarcoris lewisi

The male-produced aggregation pheromone of the stink bug Erysarcoris lewisi Distant was shown to be one of the two diastereomers of (2Z,6R)-2-methyl-6-(4′-methylenebicyclo[3.1.0]hexyl)hept-2-en-1-ol by synthesizing and bioassaying (2E,6R)-, (2E,6S)-, (2Z,6R)-, and (2Z,6S)-isomers. These were synthesized from the enantiomers of citronellal by employing an intramolecular α-ketocarbene addition to a double bond and the E-selective or Z-selective olefination of a formyl group as the key steps. A reliable method was developed for the preparation of ethyl 2-(di-o-tolylphosphono)propanoate, Ando’s reagent for Z-selective olefination.     

Synthesis and properties of <Emphasis Type="Italic">N</Emphasis>-(alkenylidene)trifluoromethanesulfonamides

N-Alkenylidenetrifluoromethanesulfonamides TfN=CH–CR=C(Me)R′ (R, R′ = H, Me) have been synthesized by reaction of N-sulfinyltrifluoromethanesulfonamide TfNSO with (E)-but-2-enal, (E)-2-methylbut- 2-enal, and 3-methylbut-2-enal. Despite greater stability of N-alkenylidenetrifluoromethanesulfonamides relative to their propargyl isomers TfNHCH₂C≡CR, no rearrangement of the latter into the former occurs due to the presence of an acidic NH proton, which hampers formation of carbon-centered anion.     

Synthesis of spiro[4.5]decane and bicyclo[4.3.0]nonane ring systems by self-cyclization of (Z)- and (E)-2-(trimethylsilylmethyl)pentadienal derivative

The two title carbon frameworks were synthesized utilizing a new type of iron-induced cyclization reaction of 2-(trimethylsilylmethyl)pentadienal. 2-Methylspiro[4.5]dec-2-en-1-one was obtained from (Z)- and (E)-4-cyclohexylidene-2-(trimethylsilylmethyl)but-2-enal. It was found that the (Z)-substrate isomerized to (E)-intermediate followed by cyclization to afford the initial product, 2-methylenespiro[4.5]dec-3-en-1-ol, which was isomerized to the above product. The cyclization of 4-(4-alkyl)cyclohexylidene-2-(trimethylsilylmethyl)but-2-enal proceeded stereoselectively. While, (E)-3-(cyclohex-1-en-1-yl)-2-(trimethylsilylmethyl)prop-2-en-1-al cyclized immediately affording 8-methylenebicyclo[4.3.0]non-9-en-7-ol. The corresponding (Z)-isomer gave several cyclization products as a complex mixture.     

Repetition of chemistry from a recently retracted paper. A cautionary note

The base-catalyzed condensation reaction between (E)-4-phenylbut-2-enal and phenylpropargyl aldehyde recently reported in the literature to provide formylcyclobutadiene was repeated under the published conditions. The product obtained was identified as (E)-5-phenyl-2-((E)-styryl)pent-2-en-4-ynal rather than the reported 2-phenyl-3-styrylcyclobutadiene-1-carboxaldehyde. The structure assignment is supported by NMR and IR data and a x-ray structure of the crystalline alcohol obtained by Luche reduction.     

A new enantioselective synthesis of the four stereoisomers of pallantione,the male-produced sex pheromone of Pallantia macunaima (Heteroptera: Pentatomidae)

In a previous study we reported the identification of the first ketone found in the Pentatomidae family, the sex attractant pheromone of the male stink bug Pallantia macunaima, (6R,10S)-6,10,13-trimethyltetradecan-2-one. Here we describe an efficient enantioselective route for the synthesis of the four stereoisomers of this pheromone. The synthesis was conceived as the connection of two chiral building blocks, employing (R)- or (S)-citronellol and methyl (S)-3-hydroxy-2-methylpropionate as the source of chirality.     

Applications of remote stereocontrol using allylstannanes: an approach to the stereoselective synthesis of aliphatic polyols

(4R,2E)-4-Benzyloxy-octa-2,7-dienyl(tributyl)stannane was transmetalated by tin(IV) chloride to generate an allyltin trichloride, which reacted with aldehydes to give (3Z)-1,5-syn-5-benzyloxynona-3,8-dien-1-ols with useful 1,5-stereocontrol. O-Benzylation, hydroboration and oxidation of the terminal double-bond of the product from 2-methylpropanal gave (5R,9S,6Z)-5,9-dibenzyloxy-10-methylundec-6-enal. Further reactions with 4-alkoxyalk-2-enylstannanes proceeded with useful 1,5-stereocontrol to give open-chain products with hydroxy or benzyloxy substituents stereoselectively disposed at remote positions along the chain.     

Absolute configuration of (-)-biflora-4,10(19),15-triene,a diterpene from a termite soldier,as determined by the synthesis of its (1R, 6S, 7S, 11R)-(+)-isomer

(1R, 6S, 7S, 11R)-(+)-Biflora-4, 10(19),15-triene was synthesized starting from (r)-(+)-citronellic acid. This enabled us to assign (1S), 6R, 7R, (11S)-stereochemistry to the naturally occurring (-)-enantiomer isolated from soldiers of the termite species Cubitermes umbratus.     

Reactions of Enone Ethylene Ketals with Methyl Diazomalonate/Bis(acetylacetonato)copper(II)

Several cyclic and acyclic enones and their ethylene ketals/acetals were reacted with dimethyl diazomalonate under bis(acetylacetonato)copper(II) catalysis. Cyclohex-2-en-1-one ( 1 ) yielded only C–H insertion products 2 and 3 , whereas but-3-en-2-one gave a cyclopropane albeit in very low yield. The ethylene ketals 6 of cyclopent-2-en-1-one and cyclohex-2-en-1-one gave the corresponding cyclopropanes 7 , which were in turn cleaved to the ketones 8 . The acetals 9 and 10 of crotonaldehyde ((E)-but-2-enal) and cinnamaldehyde ((E)-3-phenylprop-2-enal), respectively, yielded C–O insertion and [2,3]-sigmatropic rearrangement products 11b, c and 12b, c , as well as cyclopropanes 11a and 11b , all of which are polyfunctional and synthetically useful compounds.     

Asymmetric synthesis and Lewis acid mediated type II carbonyl ene cyclisations of (R)-2-isopropyl-5-methylhex-5-enal

The asymmetric synthesis of (R)-2-isopropyl-5-methylhex-5-enal in 98% ee is described. It was discovered that the key alkylation step employing an Evans chiral auxiliary and 3-methylbut-3-en-1-yl trifluoromethanesulphonate as the alkylating agent led to significant competing O-alkylation, a phenomenon not previously reported. Type II carbonyl ene cyclisation of the aldehyde with a range of Lewis acids led to either the (R,R)- or (R,S)-5-methylidenecyclohexanols without concurrent racemisation of the alpha stereogenic centre of the aldehyde. Conditions for effecting the easy racemisation of a model enantiomerically pure aldehyde, (S)-2-methylbutanal, were developed. In an effort to secure a dynamic kinetic resolution procedure, these conditions were applied to (R)-2-isopropyl-5-methylhex-5-enal. However, a competing and dominant Prins cyclisation occurred instead leading to a mixture of all possible cycloadducts, all of which were obtained in 98% ee. Any unreacted aldehyde was found to be enantiomerically pure.     

A convenient approach to (S)-2-ethylhexan-1-ol mediated by baker’s yeast

The baker’s yeast (Saccharomyces cerevisiae) mediated asymmetric bioreduction of 2-ethylhex-2-enal (1) went smoothly under a mild condition and afforded a high yield of (S)-2-ethylhexan-1-ol (2a) with excellent enantioselectivity in biphasic system.     

Synthesis of optically active forms of (Z)-14-methylhexadec-8-enal : The pheromone of female dermestid beetle

The both enantiomers of (Z)-14-methylhexadec-8-enal were synthesized starting from (R)-(+)-citronellol. The (R)-(?)enantiomer (1) was about 250 times more active than its antipode (1') when tested on dermestid beetle.     

Convenient preparation of (Z)-α-halo-α,β-unsaturated aldehydes: synthesis of a Laurencia flexilis toxin

The CrCl₂-mediated two-carbon halo-homologation of aryl, alkenyl, and aliphatic aldehydes with chloral ethyl hemiacetal or bromal affords (Z)-α-chloro- and (Z)-α-bromo-α,β-unsaturated aldehydes, respectively, in good to excellent yields and high stereoselectivity. The utility of this methodology was illustrated by a synthesis of 2-chloropentadec-2(Z)-enal, a toxin isolated from the marine red alga Laurencia flexilis.     

Determination of the absolute configuration of the male aggregation pheromone, 2-methyl-6-(4′-methylenebicyclo[3.1.0]hexyl)hept-2-en-1-ol, of the stink bug Erysarcoris lewisi (Distant) as 2Z,6R,1′S,5′S by its synthesis

Lipase-catalyzed asymmetric acetylation of a mixture of (6R,1′S,4′S,5′R)- and (6R,1′R,4′R,5′S)-7′-norsesquisabinen-4′-ol (3) afforded a separable mixture of the recovered former and the acetate of the latter. The recovered alcohol was oxidized to (6R,1′S,5′R)-sesquisabina ketone (2), whose absolute configuration could be assigned by its CD comparison with (1R,5S)-sabina ketone (4). Conversion of (6R,1′S,5′R)-sesquisabina ketone (2) to the bioactive pheromone revealed the stereostructure of the male aggregation pheromone of the stink bug Erysarcoris lewisi (Distant) to be (2Z,6R,1′S,5′S)-2-methyl-6-(4′-methylenebicyclo[3.1.0]hexyl)hept-2-en-1-ol (sesquisabinen-1-ol, 1).     

Matrix effect in the analysis of drugs of abuse from urine with desorption atmospheric pressure photoionization-mass spectrometry (DAPPI-MS) and desorption electrospray ionization-mass spectrometry (DESI-MS)

We have studied the matrix effect within direct analysis of benzodiazepines and opioids from urine with desorption electrospray ionization-mass spectrometry (DESI-MS) and desorption atmospheric pressure photoionization-mass spectrometry (DAPPI-MS). The urine matrix was found to affect the ionization mechanism of the opioids in DAPPI-MS favoring proton transfer over charge exchange reaction. The sensitivity for the drugs in solvent matrix was at the same level with DESI-MS and DAPPI-MS (LODs 0.05–6 μg mL⁻¹) but the decrease in sensitivity due to the urine matrix was higher with DESI (typically 20–160-fold) than with DAPPI (typically 2–15-fold) indicating better matrix tolerance of DAPPI over DESI. Also in MS/MS mode, DAPPI provided better sensitivity than DESI for the drugs in urine. The feasibility of DAPPI-MS/MS was then studied in screening the same drugs from five authentic, forensic post mortem urine samples. A reference measurement with gas chromatography-mass spectrometry (GC–MS) (including pretreatment) revealed 16 findings from the samples, whereas with DAPPI-MS/MS after sample pretreatment, 15 findings were made. Sample pretreatment was found necessary, since only eight findings were made from the same samples untreated.     

Electrophysiological Responses of Bactrocera kraussi (Hardy) (Tephritidae) to Rectal Gland Secretions and Headspace Volatiles Emitted by Conspecific Males and Females

Pheromones are biologically important in fruit fly mating systems, and also have potential applications as attractants or mating disrupters for pest management. Bactrocera kraussi (Hardy) (Diptera: Tephritidae) is a polyphagous pest fruit fly for which the chemical profile of rectal glands is available for males but not for females. There have been no studies of the volatile emissions of either sex or of electrophysiological responses to these compounds. The present study (i) establishes the chemical profiles of rectal gland contents and volatiles emitted by both sexes of B. kraussi by gas chromatography–mass spectrometry (GC–MS) and (ii) evaluates the detection of the identified compounds by gas chromatography–electroantennogram detection (GC–EAD) and –electropalpogram detection (GC–EPD). Sixteen compounds are identified in the rectal glands of male B. kraussi and 29 compounds are identified in the rectal glands of females. Of these compounds, 5 were detected in the headspace of males and 13 were detected in the headspace of females. GC–EPD assays recorded strong signals in both sexes against (E,E)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane, 2-ethyl-7-mehtyl-1,6-dioxaspiro[4.5]decane isomer 2, (E,Z)/(Z,E)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane, and (Z,Z)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane. Male antennae responded to (E,E)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane, 2-methyl-6-pentyl-3,4-dihydro-2H-pyran, 6-hexyl-2-methyl-3,4-dihydro-2H-pyran, 6-oxononan-1-ol, ethyl dodecanoate, ethyl tetradecanoate and ethyl (Z)-hexadec-9-enoate, whereas female antennae responded to (E,E)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane and 2-methyl-6-pentyl-3,4-dihydro-2H-pyran only. These compounds are candidates as pheromones mediating sexual interactions in B. kraussi.     

Synthesis and oxidation of (E)-1,2-diphenyl-2-(arylimino) ethanol derivatives

The compounds (E)-1,2-diphenyl-2-(phenylimino)ethanol, (E)-1,2-diphenyl-2-(p-tolylimino)ethanol, and (E)-2-((4-chlorophenyl)imino)-1,2-diphenylethanol) were synthesized by reaction of a p-substituted aniline with benzoin then oxidized with chromium trioxide–triethylamine in chloroform to give (E)-1,2-diphenyl-2-(phenylimino)ethanone, (E)-1,2-diphenyl-2-(p-tolylimino)ethanone, and (E)-2-((4-chlorophenyl)imino)-1,2-diphenylethanone in very high yield. The products were characterized by IR and NMR spectral analysis.     

Synthesis of (±)‐Trinervitadiene‐2,3‐diol

The first synthesis of trinervita‐1(15),8(19)‐dien‐2β,3α‐diol ( 2a ) and its 2α‐isomer 2b , which have been isolated from termite soldiers, where they are used as defense chemicals, is documented starting from geranylgeranioic acid in 33 steps. The route for construction of the key intermediate of the trinervitane skeleton 8 has been developed previously (Scheme 1). Noteworthy features include the efficient construction of the trinervitane framework from the corresponding bicyclic 7(16)‐secotrinervitane skeleton and Me₃SiCl (TMSCl)‐induced ring‐opening of tetrasubstituted epoxide to give the corresponding allyl alcohols (Scheme 7). The synthetic route developed in the present study seems applicable to the syntheses of other trinervitane‐type natural products.     

Asymmetric synthesis of (+)-trachyspic acid

Aldol reaction of di-tert-butyl 4-(4-methoxybenzyloxy)-2-oxobutanoate with pent-4-enal using (S)-1-(3,5-bis(trifluoromethyl)phenyl)-3-(pyrrolidin-2-ylmethyl)thiourea hydrochloride as a catalyst, followed by Pinnick oxidation and tert-butyl esterification, gave (2S,3S)-di-tert-butyl 2-(2-(4-methoxybenzyloxy)ethyl)-3-allyl-2-hydroxysuccinate in high optical purity (85% ee), from which the total synthesis of (+)-trachyspic acid, a tumor cell heparanase inhibitor, was accomplished.