Adriano Carpita

A palladium-promoted route to 3-alkyl-4-(1-alkynyl)hexa-1,5-dyn-3-enes and/or 1,3-diynes

Reaction of benzene solutions of arylacetylenes with 1 equiv. of chloroacetone and 2 equiv. of Et3N, using a mixture of (PPh3)4 Pd and CuJ as catalyst, affords 1,4-diaryl-butadiynes in very good yields. Under similar reaction conditions aliphatic 1-alkynes yield mixtures of simmetrically disubstituted 1,4-dialkyl-1,3-butadiynes and of 3-alkyl-4-(1-alkynyl)-hexa-1,5-diyn-3-enes.

Synthesis of 3-arylisocoumarins, including thunberginols A and B, unsymmetrical 3,4-disubstituted isocoumarins, and 3-ylidenephthalides via iodolactonization of methyl 2-ynylbenzoates or the corresponding carboxylic acids

3-Aryl-4-iodoisocoumarins, which were readily and efficiently prepared by regioselective iodolactonization of methyl 2-ynylbenzoates or the corresponding carboxylic acids, were used as precursors either to 3-arylisocoumarins, including naturally-occurring thunberginols A and B, or to unsymmetrical 3,4-disubstituted isocoumarins. On the other hand, (Z)- and (E)-3-iodomethylidenephthalides, which were regioselectively prepared by iodolactonization of methyl 2-ethynylbenzoate, were employed as starting materials for the stereospecific synthesis of (Z)- and (E)-3-ylidenephthalides, respectively. Some 3-arylisocoumarins and unsymmetrical 3,4-disubstituted isocoumarins showed certain cytotoxic activity against human cancer cell lines in vitro.

New procedures for the selective synthesis of 2(2H)-pyranone derivatives and 3-aryl-4-iodoisocoumarins

Abstract 5-Iodo-2(2 H )-pyranone derivatives have been selectively synthesized by reaction of stereodefined methyl 2-en-4-ynoates with iodine in MeCN, CH 2 Cl 2 or C 6 H 6 at 20°C (Method C) or by treatment of these esters with ICl in CH 2 Cl 2 at 20°C (Method B). Methods B and C proved also to be suitable for the preparation of 3-aryl-4-iodoisocoumarins from the corresponding methyl 2-(arylethynyl)benzoates. Interestingly, the high selectivity of iodolactonization of stereodefined methyl 2-en-4-ynoates by Method B allowed preparation in moderate yields of 2(2 H )-pyranone derivatives by a one-pot sequence of iodolactonization and Stille-type reactions.

Synthesis and 13C NMR characterization of some π-excessive heteropolyaromatic compounds

Abstract Several π-excessive heteropolyaromatic compounds, which contain furan and thiophen ring and are possible antifungal agents, have been synthesized in good yields according to two general methods. The first method has been used to prepare compounds possessing thiophens linked by their 2- and 5-positions, such as the ter-aryls 2b , 2d and 2a . Two precursors of these compounds have been obtained either by the Glaser reaction, or using a novel Pd-mediated reaction. The second method,which consists of the Ni-or Pd-catalyzed heteroarylation of heteroarene halides via cross-coupling with heteroaryl Grignard reagents or zinc halides,has been used to prepare the bi-aryls 1a-e , which contain two heteroaromatic units, and the ter-aryl 2c . Compound 1e has been also prepared starting from 2-(2-thienyl) furan ( 1c ) by selective lithiation, followed by bromination. The 13C NMR signals of 1a-e and 2a-d have been assigned on the basis of the literature data and by relaxation measurements. Relaxation data have been also used to obtain qualitative informations on the conformational equilibria of the bi-aryls 1a , 1c and the ter-aryls 2a-d .

Insect sex pheromones: Palladium-catalyzed synthesis of aliphatic 1,3-enynes by reaction of 1-alkynes with alkenyl halides under phase transfer conditions☆☆☆

Abstract Functionalized 1,3-enzynes of general formula 1 have been prepared in good yields by coupling reaction of 1-alkynes or ω-functionalized 1-alkynes halides in the presence of a catalytic amount of (PPh3)4Pd and Cul. The reactions, which were carried out under phase transfer conditions employing benzyltriethylammonium chloride as phase transfer agent, benzene as organic solvent and diluted aq NaOH as base, occurred with 100% stereospecificity when 1-halo-1-alkenes of defined configuration were used. Such coupling reactions have been employed to prepare some pure insect sex pheromone components or their precursors in high overall yield.

Selective synthesis of natural and unnatural 5,6-disubstituted 2(2H)-pyranones via iodolactonization of 5-substituted (Z)-2-en-4-ynoic acids

Abstract Reaction of 5-substituted ( Z )-2-en-4-ynoic acids with iodine and NaHCO 3 in CH 3 CN or with ICl in CH 2 Cl 2 affords mixtures of ( E )-5-(1-iodoylidene)-2(5 H )-furanones and 6-substituted 5-iodo-2(2 H )-pyranones in which these last compounds are the major products. The 5-iodo-2(2 H )-pyranones, which are easily separated chromatographically from the corresponding regioisomers, are able to undergo Stille-type reactions with a variety of organotin compounds to give 5,6-disubstituted 2(2 H )-pyranones in moderate to good yields. One of these compounds, i.e. 5-(1-butynyl)-2(2 H )-pyranone, has been used as direct precursor to two substances produced by fungal culture LL-11G219, which function as androgen ligands, i.e. ( Z )-5-(1-butenyl)-6-methyl-2(2 H )-pyranone and 5-butyl-6-methyl-2(2 H )-pyranone.

Selective and efficient syntheses of phototoxic 2,2′:5′,2″-terthiophene derivatives bearing a functional substituent in the 3′- or the 5-position

Abstract Efficient and selective procedures have been developed to prepare on a medium scale several phototoxic 2,2′:5′,2″-terthiophene derivatives of general formula 2 and 3, which are characterized by a functional substituent in the 3′- or the 5-position.Most of these procedures, which are based on the construction of the 2.2′:5′,2″-terthiophene moiety and involve palladium-mediated carbon-carbon bond forming reactions, allow to overcome synthetic difficulties that may be found in the synthesis of compounds 2 and 3 starting from 2,2′:5′,2″-terthiophene (1a).

Insect pheromone components: Use of 13C NMR spectroscopy for assigning the configuration of CC double bonds of monoenic or dienic pheromone components and for quantitative determination of Z/E mixtures

Abstract Several insect sex pheromone components and structural analogues have been characterized by 13C NMR spectroscopy. The evaluation of the difference between the chemical shift values of the allytic carbons present in the diunsaturated pheromone components and those of the carbons having the same position on the n-alkane chain of the corresponding saturaated compounds was used to assign the configuration of the CC double bonds present into such dienic compounds. The technique avoids the need to use the nuclear Overhausser effect; it allows quantitative evaluation, with good accuracy, of the stereoisomeric composition of mixtures of synthetic monoenic or dienic pheromone components such as (Z)- and (E)-9-tetraceden-1-yl acetate and (Z)- and (E)-9,11-dodecadien-1-yl acetate.

Dienic sex pheromones : Stereoselective syntheses of (7E,9Z)-7,9-dodecadien-1-yl acetate, (E)-9,11-dodecadien-1-yl acetate, and of (9Z), 11E)-9,11- tetradecadien-1-yl acetate by palladium-catalyzed reactions

Abstract Pure (7E,9Z-7, 9-dodecadien-1-yl acetate (1), the sex pheromone of Lobesia botrana, has been prepared in 21.6% overall yield by a reaction scheme involving; (i) the cross-coupling of (E) - 8 - (2 - tetrahydropyranyloxy) -1 - octenyldisiamylborane with 1 - bromo - 1 - butyne, in the presence of a Pd (O) catalyst and base; (ii) the acetylation of the crude product of this reaction; (iii) the (Z)-stereoselective reduction of the obtained conjugated (E)-enyn-1-yl acetate. (E)-9,11-Dodecadien-1-yl acetate (2), a sex pheromone component of Diparopsis castanea, has been analogously obtained (in 54.3% overall yield) by cross-coupling of (E) - 10 - (2 - tetrahydropyranyloxy) - 1 - decenyl borane with vinyl bromide, in the presence of a Pd (O) catalyst and base, followed by acetylation of the crude product. Compound 2, which was 87.7% chemically pure, was purified by column chromatography over SiO2-AgNO3. Chemically pure (9Z, 11E) - 9,11 - tetradecadien - 1 - yl acetate (3), a sex pheromone component of Spodoptera littoralis, has been prepared (in 30.2% overall yield) by reaction of 10 - (2 - tetrahydropyranyloxy) - 1 - decynylamagnesium bromide with (E)-1-iodo-1-butene, in the presence of a Pd (O) catalyst, followed by acetylation of the crude product and by (Z)-stereoselective reduction of the obtained (E)-enyn-1-yl acetate. The stereoisomeric purity of 1, 2 and 3 has been evaluated by glc analysis on glass capillary columns or by reverse phase hplc analysis.

(Z)-9-tricosene identified in rectal gland extracts of Bactrocera oleae males: first evidence of a male-produced female attractant in olive fruit fly.

It is well-known that Bactrocera oleae (olive fruit fly) females attract conspecific males by using 1,7-dioxaspiro[5,5]undecane (1) as the main component of their sex pheromone, and that 1 is produced in the female rectal gland. Although some authors have claimed that B. oleae males also attract females, to date no male-produced female attractants have been found in this species. In this paper, we report the first identification of a substance unique to males and able to attract females. The findings of the study include the following: (1) females responded in a bioassay to hexane extracts obtained from rectal glands of 15-day-old B. oleae males, (2) the presence of (Z)-9-tricosene (2) was consistently and unambiguously identified in these extracts using gas chromatography (GC) and GC-mass spectrometry methods, (3) in preliminary bioactivity tests, low doses (equivalent to a few males) of chemically and stereoisomerically pure synthetic (Z)-9-tricosene (2) attracted olive fruit fly females. Interestingly, compound 2, commonly called muscalure, is also a well-known component of the house fly (Musca domestica) sex pheromone.