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Synthesis of acyclic insect pheromones from cycloalkanones via acetylenic lactones

Abstracts

Figure 1 describes a general method for the preparation of insect pheromones. Several members of the title compounds, along with their geometric and/or positional isomers, have been prepared from Z-lactones 2a-d, which are easily available from the corresponding acetylenic lactones 1a-d, prepared earlier from cycloalkanones. The Z to E isomerization of alkenyl acetates 6a-d to 8a-d was carried out both by a catalytic technique (NaNO2, HNO3, D) and the chemical inversion procedure (NBS, TFA; NaI, DMF, D). (E)-6-Decenyl alcohol (7b) was also prepared from the acetylenic ester 15b by the trans reduction with LiAlH4 in refluxing diglyme. decyl acetate (18) and hexadecyl acetate (19), pheromone components of the turnip moth (Agrotis segetum) and the male butterfly Lycorea ceres ceres, respectively, were obtained by the catalytic hydrogenation (Pd, H2) of the corresponding Z-alkenyl acetates.

insect pheromones; Z-lactones; acetylenic lactones; cycloalkanones


A Fig. 1 descreve um método geral para preparação de feromônios de insetos. Vários componentes de feromônios de insetos, junto de seus isômeros geométricos e/ou posicionais, foram preparados a partir de Z-lactonas 2a-d, que são facilmente acessíveis pela hidrogenação estereosseletiva (Lindlar Pd, H2) dos precursores acetilênicos 1a-d, sendo estes já sintetizados a partir de cicloalcanonas. A isomerização de acetatos de Z-alquenilas 6a-d aos respectivos esteres de E-alquenilas 8a-d, foi realizada tanto pela técnica catalítica (NaNO2, HNO3, D) como pelo método de inversão química (NBS, TFA; NaI, DMF, D). O álcool (E)-6-decenílico (7b) foi também preparado diretamente do ester acetilênico (15b) pela redução, em trans, com hidreto de lítio-alumínio (LiAlH4), por refluxo em diglima. Os acetatos de decila (18) e hexadecila (19), componentes dos feromônios de mariposa do nabo (Agrotis segetum; turnip moth) e da borboleta Lycorea ceres ceres, respectivamente, foram obtidos pela hidrogenação catalítica (Pd, H2) dos acetatos de Z-alquenilas correspondentes.


ARTICLE

Synthesis of acyclic insect pheromones from cycloalkanones via acetylenic lactones

Jaswant Rai Mahajan,* Inês Sabioni Resck

Departamento de Química, Universidade de Brasilia, 70.910-900 Brasilia - DF, Brazil

Received: August 28, 1996

A Fig. 1 descreve um método geral para preparação de feromônios de insetos. Vários componentes de feromônios de insetos, junto de seus isômeros geométricos e/ou posicionais, foram preparados a partir de Z-lactonas 2a-d, que são facilmente acessíveis pela hidrogenação estereosseletiva (Lindlar Pd, H2) dos precursores acetilênicos 1a-d, sendo estes já sintetizados a partir de cicloalcanonas. A isomerização de acetatos de Z-alquenilas 6a-d aos respectivos esteres de E-alquenilas 8a-d, foi realizada tanto pela técnica catalítica (NaNO2, HNO3, D) como pelo método de inversão química (NBS, TFA; NaI, DMF, D). O álcool (E)-6-decenílico (7b) foi também preparado diretamente do ester acetilênico (15b) pela redução, em trans, com hidreto de lítio-alumínio (LiAlH4), por refluxo em diglima. Os acetatos de decila (18) e hexadecila (19), componentes dos feromônios de mariposa do nabo (Agrotis segetum; turnip moth) e da borboleta Lycorea ceres ceres, respectivamente, foram obtidos pela hidrogenação catalítica (Pd, H2) dos acetatos de Z-alquenilas correspondentes.

Figure 1 describes a general method for the preparation of insect pheromones. Several members of the title compounds, along with their geometric and/or positional isomers, have been prepared from Z-lactones 2a-d, which are easily available from the corresponding acetylenic lactones 1a-d, prepared earlier from cycloalkanones. The Z to E isomerization of alkenyl acetates 6a-d to 8a-d was carried out both by a catalytic technique (NaNO2, HNO3, D) and the chemical inversion procedure (NBS, TFA; NaI, DMF, D). (E)-6-Decenyl alcohol (7b) was also prepared from the acetylenic ester 15b by the trans reduction with LiAlH4 in refluxing diglyme. decyl acetate (18) and hexadecyl acetate (19), pheromone components of the turnip moth (Agrotis segetum) and the male butterfly Lycorea ceres ceres, respectively, were obtained by the catalytic hydrogenation (Pd, H2) of the corresponding Z-alkenyl acetates.

Keywords: insect pheromones, Z-lactones, acetylenic lactones, cycloalkanones

Introduction

Pheromones are an important and a rapidly growing class of biologically active organic compounds. A large proportion of pheromones isolated from a variety of insects exemplifies diversely functionallized acyclic compounds, which have been synthesized by several routes1-3. While earlier methodologies employed for the construction of the acyclic skeleton involved mainly the acetylenic chemistry and olefin formation by the Wittig or related reactions1. More recently, there has been an increasing emphasis on the use of diverse methods for improved isomeric purity of the E or Z product and for those leading to the optically active pheromones2,3.

We have recently initiated a different approach to these acyclic compounds by the systematic elaboration of cycloalkanones, where the variable size of the starting ketone is exploited to generate the triple or the double bond of the desired product in a regiospecific and stereoselective manner4 (Scheme 1).

We have already reported our preliminary results on the conversion of cyclohexanone, involving the transformation of an a-chloroketone function into an acetylenic linkage (RCHClCOR ® RCºCR), to both the Z and E series of C9 pheromones5. A recent publication6 described the preparation of Z and E macrolides from the acetylenic lactones71a-d, whilst we report their transformation into several members of the title compounds and their geometric or positional isomers, as illustrated in Scheme 2.


Results and Discussion

Methanolysis of the Z-lactones6 2a-d gave the corresponding hydroxy-esters 3a-d, which on mesylation8 furnished the respective mesylates 4a-d. Lithium aluminum hydride reduction of the latter in ether afforded the Z-alkenols 5a-d, which were acetylated to the corresponding acetates 6a-d. Of these, (Z)-5-decenyl acetate (6a) is the pheromone component of the turnip moth (Agrotis segetum)3, while (Z)-8-dodecenyl acetate (6c) constitutes the sex pheromone of the oriental fruit moth (Grapholita molesta)3. These two compounds have been synthesized earlier3.

Both the catalytic isomerization (NaNO2, HNO3)9 and the chemical inversion (TFA, NBS; NaI, DMF, D)10 of the Z alkenyl acetates 6a-d worked well with these acyclic compounds, leading to the corresponding E acetates 8a-d in good (90-95%) yield. Nevertheless, the catalytic technique9 (2M NaNO2 , 2M HNO3 , 70-75 °C, 1 h) is far more convenient and economical. Among the E compounds 8a-d, only (E)-8-dodecenyl acetate (8c) is a minor component of the pheromone of the oriental fruit fly (Grapholita molesta), mentioned earlier3.

We would like to stress here that the alternative route to these E alkenyl acetates 8a-d, through the respective transformations of the E lactones (dashed arrows in Scheme 2-A), is rather limited and less attractive, because the Z to E isomerization works better in the acyclic compounds as compared with the cyclic ones (lactones), as discussed elsewhere6.

Another path was tested with the opening of the acetylenic lactone 1b. However, reduction of the mesiloxy-ester 13b, with LiAlH4 in ether, required a much lower initial reaction temperature (-100 °C as compared with the usual -15 °C), but still gave a mixture of the desired alcohol 14b and the unwanted diol 16b. The latter could be separated by column chromatography of the corresponding acetates 15b and 17b. Despite this drawback, this path has the advantage of leading to both the Z and E isomers directly from the acetylenic precursor. Thus, semi-hydrogenation (H2, Lindlar cat.) of 15b furnished (Z)-6-decenyl acetate (6b), while its trans reduction with LiAlH4 in refluxing diglyme11 gave directly (E)-6-decen-1-ol (7b), which was converted into the respective acetate 8b (Scheme 2-B).

Apart from furnishing the acetylenic intermediates as well as both the Z and E alkenyl alcohols and their esters, the present methodology also opens an access to the saturated pheromones, either by the full hydrogenation of the unsaturated precursores or by the systematic elaboration of the saturated lactones. We chose to prepare decyl acetate (18) and hexadecyl acetate (19), pheromone components of the turnip moth (Agrotis segetum)12 and the male butterfly Lycorea ceres ceres13, respectively, from the corresponding Z-alkenyl acetates (Scheme 2-C).

The infrared and 90 MHz 1H NMR spectra do not clearly differentiate between the Z and E alkenyl acetates (6a-d / 8a-d). Consequently, we resorted to their 200/50 MHz 1H- and 13C- spectra (PND, DEPT, 1H x 1H and 1H x 13C COSY, etc.), where the most evident distinguishing feature, as expected, was the chemical shift of the allylic carbon atoms, which are 4 to 6 ppm upfield in the Z compounds as compared with the respective atoms in the E isomers (Tables 1 and 2)14. Moreover, close examination of the olefinic carbon atoms in the PND spectra revealed that all the E alkenyl acetates (8a-d) were contaminated with 5-10% of the corresponding Z isomer, while only the (Z)-8-dodecenyl acetate (6c) and (Z)-12-hexadecenyl acetate (6d) contained 5-10% of the respective E compound, as also present in the precursor Z-lactones62c,d.

Experimental

Reagent grade chemicals and solvents were used as received from the commercial suppliers, unless noted otherwise. All reactions were monitored routinely by thin layer chromatography (TLC: silica gel, revealed by I2 vapours). Organic extracts were dried over anhydrous Na2SO4 and evaporated under reduced pressure on a rotary evaporator. IR spectra of all liquid samples were recorded on a Nicolet 5ZDX-FT spectrometer as neat films. Routine 1H-NMR spectra, reported in the experimental text, were obtained on a Varian EM-390 (90 MHz) instrument as CCl4 solutions, while the high resolution 1H- and 13C- spectra (PND, DEPT, 1Hx1H and 1Hx13C COSY, etc.) for the Z- and E-alkenyl acetates (Tables 1 and 2) were recorded in CDCl3 on a Bruker AC-200 (200/50 MHz) spectrometer. Bransonic ultrasonic cleaner (Model 1210 or 2210; 47 ± 6 KHz) was used to conduct the semi-hydrogenations. Temperatures in the short path distillations refer to the air bath. Other experimental details are given below.

Methanolysis of Z-Lactones 2a-d. General procedure

A solution of 2a-d (5 mmol) in MeOH (20 ml), containing NaOMe (10 mL, 0.13 mM) and protected with a CaCl2 tube, was refluxed (N2) for 20-24 h. After evaporating excess of the solvent, distilled water (20 ml) was added and the mixture extracted with ethyl acetate (3 x 30 ml). The combined extract was washed with water (20 ml) and brine (2 x 20 mL). Drying and evaporation of the solvent furnished the crude hydroxy-esters 3a-d as yellowish liquids (~4.5 mmol; ~90%), practically pure by TLC , which were used in the next step, after the usual spectral identification.

Methyl (Z)-9-Hydroxy-5-decenoate 3a

IR (n): 3419, 1739, 1245, 1220, 1202, 1128 cm-1. 1H-NMR (d): 1.16 (d, J = 6 Hz, 3H, CH3), 1.2-1.9 (m, 4H, 2CH2), 1.9-2,5 (m, 6H, 3CH2), 3,49 (s, 1H, OH), 3.6-3.9 (m, 4H, containing a singlet at 3.65, OCH3 and CH), 5.15-5.65 (m, 2H, olefinic).

Methyl (Z)-9-Hydroxy-6-decenoate 3b

IR (n): 3496, 1740, 1261, 1209, 1120 cm-1. 1H-NMR (d): 1.12 (d, J = 6 Hz, 3H, CH3 ), 1.2-1.9 (m, 4H, 2CH2), 1.9-3.0 (m, 7H, 3CH2 and OH) , 3.5-3.9 (m, 4H, containing a singlet at 3.62, OCH3 and CH), 5.2-5.7 (m, 2H, olefinic).

Methyl (Z)-11-Hydroxy-8-dodecenoate 3c

IR (n): 3425, 1740, 1254, 1201, 1119 cm-1. 1H-NMR (d): 1.13 (d, J = 6 HZ , 3H, CH3), 1.2-1.9 (m, 8H, 4CH2), 1.9-2.5 (m, 6H, 3CH2), 3.3 (s, 1H, OH), 3.6-4.1 (m, 4H, containing a singlet at 3.62, OCH3 and CH), 5.3-5.7 (m, 2H, olefinic).

Methyl (Z)-15-Hydroxy-12-hexadecenoate 3d

IR (n): 3435, 1740, 1253, 1208, 1120 cm-1 . 1H-NMR (d): 1.16 (d, J = 7 Hz, 3H, CH3), 1.2-1.9 (m, 16H, 8CH2), 1.9-2.5 (m, 6H, 3CH2), 2.77 (s, 1H, OH), 3.6-4.0 (m, 4H, containing a singlet at 3.63, OCH3 and CH), 5.25-5.65 (m, 2H, olefinic).

Mesylation of the Hydroxy-Esters 3a-d. General procedure

To a stirred solution of the hydroxy-ester 3a-d (4.5 mmol) and triethylamine (0,95 mL, 690 mg, 6.83 mmol) in CH2Cl2 (20 mL), cooled to -15 °C and under anhydrous conditions, was added slowly a solution of H3CSO2Cl (0.4 mL, 592 mg, 5.17 mmol) in CH2Cl2 (10 mL). The reaction mixture was stirred for 3 h, when it was diluted with more CH2Cl2 (50 mL) and washed with water (3 x 20 mL) and brine (20 mL). Drying and evaporation of solvent gave yellowish, viscous liquids 4a-d (4.0-4.3 mmol; 90-95%), showing one spot on TLC plates. A rapid passage through a small column of Florisil (3-5 g), in CH2Cl2 (20-30 mL), afforded purer samples which were characterized by their spectra and subsequently reduced with LiAlH4.

Methyl (Z)-9-Mesyloxy-5-decenoate 4a

IR (n): 1736, 1354, 1174 cm-1. 1H-NMR (d): 1.38 (d, J ~ 6 Hz, 3H, CH3), 1.4-1.9 (m, 4H, 2CH2), 1.9-2.5 (m, 6H, 3CH2), 3.0 (s, 3H, SO3CH3), 3.62 (s, 3H, OCH3), 4,75 (sextet, J ~ 6 Hz, 1H, CH), 5.2-5.6 (m, 2H, olefinic).

Methyl (Z)-9-Mesyloxy-6-decenoate 4b

IR (n): 1737, 1355, 1207, 1177 cm-1. 1H-NMR (d): 1.1-1.9 (m, 7H, containing a doublet at 1.39, J ~ 6 Hz, CH3 and 2CH2), 1.9-2.7 (m, 6H, 3CH2), 2.97 (s, 3H, SO3CH3), 3.63 (s, 3H, OCH3), 4.75 (sextet, J ~ 6 Hz, 1H, CH), 5.2-5.8 (m, 2H, olefinic).

Methyl (Z)-11-Mesyloxy-8-dodecenoate 4c

IR (n): 1737, 1357, 1253, 1176 cm-1. 1H-NMR (d): 1.1-1.9 (m, 11H, containing a doublet at 1.4, J ~ 6 Hz, CH3 and 4CH2), 1.9-2.7 (m, 6H, 3CH2), 2.95 (s, 3H, SO3CH3), 3.63 (s, 3H, OCH3), 4,75 (sextet, J ~ 6 Hz, 1H, CH), 5.2-5.8 (m, 2H, olefinic).

Methyl (Z)-15-Mesyloxy-12-hexadecenoate 4d

IR (n): 1738, 1358, 1252, 1176 cm-1. 1H-NMR (d): 1.1-1.9 (m, 19H, containing a doublet at 1.37, J ~ 7 Hz, CH3 and 8 CH2), 1.9-2.7 (m, 6H, 3CH2), 2.97 (s, 3H, SO3CH3), 3.6(s, 3H, OCH3), 4.75 (sextet, J ~ 6 Hz, 1H, CH), 5.2-5.8 (m, 2H, olefinic).

Reduction of Mesyloxy-esters 4a-d. General procedure

To a stirred suspension of LiAlH4 (608-646 mg, 16-17 mmol) in ether (40-50 mL), cooled to -15 °C, was added dropwise a solution of the mesyloxy-ester 4a-d (4.0-4.3 mmol) in the same solvent (10 mL). The reaction mixture was stirred until it attained r. t. (2-3 h), when it was gently refluxed for 14-16 h. After cooling, it was carefully decomposed with small pieces of ice and extracted with ethyl acetate (3 x 30 mL), the combined extract being successively washed with dil. HCl (20 mL), satd. solution of NaHCO3 (20 mL) and brine (20 mL). Drying and evaporation furnished yellowish liquids (3.6-3.8 mmol; 90-95%), which were acetylated after spectral characterization.

(Z)-5-Decenol 5a

IR (n): 3336, 1056 cm-1. 1H-NMR (d): 0.94 (deformed t, 3H, CH3), 1.1-1.8 (m, 8H, 4CH2), 1.8-2.4 (m, 4H, 2CH2), 3.56 (t, J = 6 Hz, 2H, CH2O), 4.5 (br. s, 1H, OH), 5.15-5.60 (m, 2H, olefinic).

(Z)-6-Decenol 5b

IR (n): 3338, 1054 cm-1. 1H-NMR (d): 0.88 (t, J = 7 Hz, 3H, CH3), 1.1-1.8 (m, 8H, 4CH2), 1.8-2.3 (m, 4H, 2CH2), 3.5 (t, J = 6 Hz, 2H, CH2O), 3.8 (br. s, 1H, OH), 5.1-5.5 (m, 2H, olefinic).

(Z)-8-Dodecenol 5c

IR (n): 3332, 1058 cm-1. 1H-NMR (d): 0.90 (t, J = 7 Hz, 3H, CH3), 1.1-1.8 (m, 12H, 6CH2), 1.8-2.3 (m, 4H, 2CH2), 3.52 (t, J = 6 Hz, 2H, CH2O), 4.0 (br. s, 1H, OH), 5.15-5.55 (m, 2H, olefinic).

(Z)-12-Hexadecenol 5d

IR (n): 3334, 1056 cm-1. 1H-NMR (d): 0.92 (t, J~7 Hz, 3H, CH3), 1.1-1.8 (m, 20H, 10CH2), 1.8-2.3 (m, 4H, 2CH2), 3.52 (t, J = 6 Hz, 2H, CH2), 3.93 (br. s, OH), 5.1-5.5 (m, 2H, olefinic).

Acetylation of Z-Alkenols 5a-d. General procedure

A solution of 5a-d (3.6-3.8 mmol) in acetic anhydride (3.2-3.4 mL, 3.5-3.7 g, 34-36 mmol), containing 6-7 drops of pyridine and protected with a CaCl2 tube, was heated on a water bath (80-90 °C) for 3 h, after which water (15-20 mL) was added and the cooled reaction mixture extracted with hexane (3 x 30 mL). The combined extract was washed with dil. HCl (10 mL), satd. solution of NaHCO3 (10 mL), and brine (20 mL). Drying and evaporation gave the desired acetates 6a-d, as colorless liquids, possessing pleasant odor. Short path distillation (6a-c: 110-120 °C/5 Torr; 6d: 110-120 °C/0.5 Torr) furnished the pure samples in 85-90% yield.

(Z)-5-Decenyl Acetate3 6a

Colorless liquid (641 mg; ~90% yield). IR (n): 1745, 1234 cm-1. 1H-NMR (d): 0,9 (deformed t, J ~ 6 Hz, 3H, CH3), 1.1-1.8 (m, 8H, 4CH2), 1.8-2.5 (m, 7H, containing a singlet at 1.96, AcO and 2CH2), 4,0 (t, J = 6 Hz, 2H, CH2O), 5.15-5.55 (m, 2H, olefinic).

(Z)-6-Decenyl Acetate 6b

Colorless liquid (652mg; 90%). IR (n): 1743, 1236 cm-1. 1H-NMR (d): 0.92 (t, J ~ 6 Hz, 3H, CH3), 1.1-1.9 (m, ~10H, 5CH2), 1.9-2.4 (m, ~5H, containing a singlet at 2.0, AcO and CH2), 4,0 (t, J = 6 Hz, 2H, CH2O), 5.1-5.6 (m, 2H, olefinic).

(Z)-8-Dodecenyl Acetate3 6c

Colorless liquid (691mg; 85%). IR (n): 1743, 1240 cm-1. 1H-NMR (d): 1.0 (t, J = 6 Hz, 3H, CH3), 1.2-1.8 (m, ~12H, 6CH2), 1.8-2.5 (m, ~7H, containing a singlet at 2.05, AcO and 2CH2), 4,05 (t, J = 6 Hz, 2H, CH2O), 5.2-5.6 (m, 2H, olefinic).

(Z)-12-Hexadecenyl Acetate 6d

Colorless liquid (873 mg; 86%). IR (n): 1743, 1237 cm-1. 1H-NMR (d): 0.89 (t, J ~ 7 Hz, 3H, CH3), 1.1-1.8 (m, 20H, 10CH2), 1.8-2.6 (m, 7H, having a singlet at 1.95, AcO and 2CH2), 4,0 (t, J ~ 7 Hz, 2H, CH2O), 5.15-5.60 (m, 2H, olefinic).

200/50 MHz spectra of these acetates are shown in Table 1.

Catalytic Isomerization of Z Acetates 6a-d into E Isomers 8a-d. General procedure

Sodium nitrite solution (2M, 0.1mL) and 2M HNO3 (0.2 mL) were added to the Z acetate 6a-d (1 mmol), kept under N2 atmosphere. The resulting yellowish mixture was stirred vigorously and heated to 70-75 oC for 1 h. After cooling and dilution with water (10 mL), it was extracted with hexane (3 x 20 mL), the combined extract being washed with satd. soln. of NaHCO3 (10 mL) and brine (10 mL). Drying and evaporation gave yellowish liquids in 95-100% yield. Short path distillation (8a-c: 110-120 °C/5 Torr; 8d: 110-120 °C/0.5 Torr) afforded colorless liquids (90-95%).

(E)-5-Decenyl Acetate 8a

IR (n): 1744, 1240, 970 cm-1. 1H-NMR (d): 0.90 (deformed t, J ~ 6 Hz, 3H, CH3), 1.1-1.9 (m, 8H, 4CH2), 1.9-2.3 (m, 7H, having a singlet at 2.03, AcO and 2CH2), 4.0 (t, J = 6 Hz, 2H, CH2O), 5.15-5.65 (m, 2H, olefinic).

(E)-6-Decenyl Acetate 8b

IR (n): 1743, 1238, 969 cm-1. 1H-NMR (d): 0.86 (t, J ~ 7 Hz, 3H, CH3), 1.1-1.8 (m, 8H, 2CH2), 1.8-2.3 (m, 7H, showing a singlet at 1.95, AcO and 2CH2), 3.98 (t, J ~ 6 Hz, 2H, CH2O), 5.1-5.6 (m, 2H, olefinic).

(E)-8-Dodecenyl Acetate3 8c

IR (n): 1743, 1240, 969 cm-1. 1H-NMR (d): 0.94 (t, J ~ 7 Hz, 3H, CH3), 1.20-1.85 (m, 12H, 6CH2), 1.85-2.5 (m, 7H, having a singlet at 2.02, AcO and 2CH2), 4.04 (t, J = 6 Hz, 2H, CH2)), 5.2-5.6 (m, 2H, olefinic).

(E)-12-Hexadecenyl Acetate 8d

IR (n): 1743, 1238, 967 cm-1. 1H-NMR (d): 0.88 (deformed t, 3H, CH3), 1.1-1.8 (m, 20H, 10CH2), 1.8-2.6 (m, 7H, having a singlet at 1.97, AcO and 2CH2), 4.0 (t, J = 6 Hz, 2H, CH2O), 5.15-5.65 (m, 2H, olefinic).

Higher field spectra of these acetates are shown in Table 2.

Chemical Inversion of Z Acetates (6a-d) to E Isomers (8a-d). General procedure

Compound 6a-d (0.5 mmol) was added slowly to a cold (0 °C) and stirred solution of NBS (107 mg, 0.6 mmol) in TFA (0.75 mL, 1.1 g, 9.74 mmol), protected with a drying tube. After stirring for 30 min, the reaction mixture was diluted with water (10 mL) and extracted with hexane (3 x 10 mL), the extract being washed with water (5 x 10 mL) and brine (10 mL). Usual work-up furnished the crude adducts, in almost quantitative yield, showing characteristic absorptions around 1785 and 1740 cm-1.

The crude product dissolved in DMF (2 mL) and containing NaI (338 mg, 2.25 mmol) was heated at 90 °C for 20-22 h. After cooling, a dil. solution of NaHSO3 (10 mL) was added and the whole extracted with hexane (3 x 10 mL). Usual work-up gave brown liquids, which on short path distillation furnished the E acetates 8a-d, in 90-95% yield, as colorless liquids, identical (IR and 1H-NMR) with the respective products obtained earlier by the catalytic procedure.

Methanolysis of the Acetylenic Lactone 1b

A solution of 1b (830 mg, 5 mmol) in MeOH (20 mL), containing NaOMe (0.13 mM, 10 mL), was refluxed for 2-3 h, when it was worked-up as described earlier for the methanolysis of Z lactones, obtaining the hydroxy-ester 12b, a yellowish liquid, in 90% yield (891 mg). IR (n): 3433, 1739, 1283, 1264, 1216, 1177 cm-1. 1H-NMR (d): 1.2 (d, J = 6 Hz, 3H, CH3), 1.3-2.0 (m, 4H, 2CH2), 2.0-2.6 (m, 6H ,3CH2), 3.2-4.2 (m, 5H, having a singlet at 3.64, OCH3, CH,OH).

The crude product (~890 mg) was mesylated with MsCl (0.4 mL, 592 mg, 5.17 mmol) and Et3N (0.95 mL) in CH2Cl2 (30 mL), as described earlier, to obtain the mesyloxy-ester 13b as a yellowish liquid (1.24 g; 100%). After a quick passage through a small column of Florisil® (3-5 g) in CH2Cl2 (20-30 mL), it was characterized by its spectra. IR (n): 1736, 1354, 1212, 1176 cm-1. 1H-NMR (d): 1.3-2.0 (m, 7H, showing a doublet at 1.52, J = 6 Hz, CH3 and 2CH2), 2.0-2.5 (m, 4H, 2CH2), 2.5-2.8 (m, 2H, CH2), 3.08 (s, 3H, SO3CH3), 3.68 (s, OCH3), 4.8 (sextet, J = 6 Hz, 1H, CH).

Reduction of the Mesyloxy-Ester 13b

A solution of ester 13b (1.2 g; 4.5 mmol) in anhydrous ether (40 mL) was added slowly to a stirred suspension of LiAlH4 (684 mg, 18 mmol) in ether (10 mL), kept at -100 °C (liquid N2 and EtOAc). After allowing the reaction mixture to attain r. t. (2-3 h), it was gently refluxed for 14-16 h. Usual work-up, as described in the earlier cases, furnished a yellowish liquid (770 mg), showing two principal spots on TLC plate. Spectral analysis revealed these as the desired alcohol 14b and unwanted diol 16b. IR (n): 3349, 1161, 1073, 1052 cm-1. 1H-NMR (d): 0,97 (t, J ~ 7 Hz, H3C-CH2), 1.2 (d, J ~ 6 Hz, H3C-CH-O) 1.2-2.0 (m, methylenes), 2.0-3.0 (m, methylenes), 3.53 (~t, CH2O), 3.7-4.0 (m, having a singlet at 3.8, OH and CH).

The above mixture was acetylated with Ac2O (4.3 mL) and pyridine (8 drops), under the usual conditions, and the resulting product (1.1 g) chromatographed, under reduced pressure,15 over silica gel 60G (15 g), eluted with hexane-EtOAc (98:2), obtaining the acetylenic monoacetate 15b (690 mg; 70%) and diacetate 17b (340 mg; 27%).

6-Decynyl Acetate 15b (Colorless liquid)

IR (n): 1742,1238 cm-1. 1H-NMR (d): 0.98 (t, J = 6 Hz, 3H, CH3), 1.2-1.9 (m, 8H, 4CH2), 1.9-2.5 (m, 7H, containing a singlet at 2.0, AcO and 2CH2), 4.03 (t, J = 6 Hz, 2H, CH2O).

1,9-Diacetoxy-6-decyn 17b (Colorless liquid)

IR (n): 1740, 1242 cm-1. 1H-NMR (d): 1.32 (t, J = 6 Hz, 3H, CH3), 1.4-1.9 (m, 6H, 3CH2), 1.9-2.7 (m, 10H, showing a singlet at 2.03, 2AcO and 2CH2), 4.05 (t, J = 6 Hz, 2H, CH2O), 4.9 (sextet, J = 6 Hz ,1H, CH).

Semi-hydrogenation6 of 6-Decynyl Acetate (15b)

Compound 15b (196 mg, 1 mmol), Lindlar catalyst (60 mg) and hexane (10 mL) were put in a pear-shaped flask, which was connected to a balloon filled with H2 (~500 mL). After the usual purging with H2 (3 times) the reaction flask was placed in the center of an ultrasound bath and irradiated for 4 h, when there was no more starting alkyne 15b, as detected by GC analysis (FFAP column, 200 °C). Filtration of the catalyst and evaporation of the solvent gave a colorless liquid, which on short path distillation (110-120 °C/5 Torr) furnished an analytical sample (194 mg; 98%), identical in all respects (TLC, IR, 1H-NMR) with (Z)-6-decenyl acetate (6b), prepared earlier by an alternative route.

Reduction of 6-Decynyl Acetate (15b) to (E)-6-Decenyl Alcohol (7b)

A solution of compound 15b (196 mg, 1 mmol) in diglyme (5 mL) was added dropwise to a magnetically stirred suspension of LiAlH4 (152 mg, 4 mmol) in diglyme (10 mL), cooled to 0 °C. After attaining r. t., the reaction mixture was refluxed gently for 24 h, when it was cooled and decomposed carefully with small pieces of ice. Extraction with hexane (3 x 20 mL) and usual work-up afforded the (E)-6-decenol (7b), which was acetylated to the corresponding acetate under the usual conditions descrided earlier. Short path distillation (110-120 °C/5 Torr) gave the pure compound 8b (190 mg; 95%), identical (TLC, IR, 1H-NMR) with the product obtained earlier by the isomerization of Z isomer 6b.

Decyl Acetate12 (18)

A solution of (Z)-6-decenyl acetate (6b: 198 mg, 1 mmol) in hexane (10 mL), containing 10% Pd-C (20-30 mg), was subjected to hydrogenation (2 atm) in a Parr apparatus for 2-3 h, when there was no more of the starting material. Usual work-up furnished the product in a quantitative yield, while short path distillation (110-120 °C/5 Torr) afforded an analytical sample. IR (n): 1744, 1238 cm-1. 1H-NMR (d): 0.92 (deformed t, J ~ 6 Hz, 3H, CH3), 1.1-1.8 (m, 16H, 8CH2), 1.97 (s, 3H, AcO), 4.0 (t, J = 6 Hz, 2H, CH2O).

Hexadecyl Acetate13 (19)

Was obtained from (Z)-12-hexadecenyl acetate (6d), exactly in the manner described above. IR (n): 1744, 1237 cm-1. 1H-NMR (d): 0.89 (deformed t, 3H, CH3), 1.28 (~s, 28H, 14CH2), 1.97 (s, 3H, OAC), 4.0 (t, J~6 Hz, 2H, CH2O).

Acknowledgments

We thank the Brazilian National Research Council (CNPq), the University of Brasília (UnB) and the "Fundação de Amparo à Pesquisa - DF" (FAP-DF) for partial support of this work. We also thank Professors R. Braz-Filho and M.G. Carvalho (UFRRJ) for the high resolution and 2D spectra of these compounds.

References

1. a) Rossi, R. Synthesis 1977, 817; b) Henrick, C.A. Tetrahedron 1977, 33, 1845.

2. Mori, K. Tetrahedron 1989, 45, 3223.

3. Mori, K. In The Total Synthesis of Natural Products, Vol. 9; Apsimon, J.; Ed.; Wiley; New York, 1992, and the pertinent references cited therein.

4. a) Mahajan, J.R. In Organic Synthesis in Brazil: An Overview; Comasseto, J.V.; Ferreira, J.T.B.; Ed.; DOT Editoração Eletrônica & Multimídia; São Carlos - SP, 1994; pp 79-87; b) Mahajan, J.R. ICOS 10, Bangalore-India, 1994; ABSTRACTS: ISP-27, P 81; c) Mahajan, J.R.; Resck, I.S.; 6th BMOS, USP-SP, 1994; ABSTRACTS: p 94; d) Mahajan, J.R.; J. Braz. Chem. Soc. 1996, 7, 297.

5. a) Mahajan, J.R.; Tresvenzol, L.M.F. J. Braz. Chem. Soc. 1993, 4, 179; b) Mahajan, J.R.; Resck, I.S.; Aspesi, G.H. 17th Annual Meeting of SBQ 1994; Abstracts: QO-041.

6. Mahajan, J.R.; Resck, I.S. Synth. Commun. 1996, 26, 3809.

7. a) Mahajan, J.R.; Resck, I.S. J. Chem. Soc., Chem. Commun. 1993, 1748; b) Resck, I.S. PhD Thesis 1995; QUI-IE-UNB.

8. Crossland, R.K.; Servis, K.L. J. Org. Chem. 1970, 35, 3195.

9. Sonnet, P.E. J. Org. Chem. 1974, 39, 3793.

10. Sonnet, P.E. J. Org. Chem. 1980, 45, 154.

11. Schwarz, M.; Graminski, G.F.; Waters, R.M. J. Org. Chem. 1986, 51, 260.

12. Olsson, A.-M.; Jonsson, J.A.; Thelin, B.; Liljefors, T. J. Chem. Ecol. 1983, 9, 375.

13. a) Meinwald, J.; Meinwald, Y.C. J. Am. Chem. Soc. 1966, 88, 1305; b) Meinwald, J.; Meinwald, Y. C.; Wheeler, J.W.; Eisner, T. Science 1966, 151, 583.

14. Mahajan, J.R.; Resck, I.S.; Braz-Filho, R.; Carvalho, M.G. 5th Meeting of NMR Users (V-AUREMN), Angra dos Reis-RJ, 1995; Abstracts: p 38; , pp 123-132.

  • 1. a) Rossi, R. Synthesis 1977, 817;
  • b) Henrick, C.A. Tetrahedron 1977, 33, 1845.
  • 2. Mori, K. Tetrahedron 1989, 45, 3223.
  • 3. Mori, K. In The Total Synthesis of Natural Products, Vol. 9; Apsimon, J.; Ed.; Wiley; New York, 1992, and the pertinent references cited therein.
  • 4. a) Mahajan, J.R. In Organic Synthesis in Brazil: An Overview; Comasseto, J.V.; Ferreira, J.T.B.; Ed.; DOT Editoração Eletrônica & Multimídia; São Carlos - SP, 1994; pp 79-87;
  • b) Mahajan, J.R. ICOS 10, Bangalore-India, 1994; ABSTRACTS: ISP-27, P 81;
  • c) Mahajan, J.R.; Resck, I.S.; 6th BMOS, USP-SP, 1994; ABSTRACTS: p 94;
  • d) Mahajan, J.R.; J. Braz. Chem. Soc 1996, 7, 297.
  • 5. a) Mahajan, J.R.; Tresvenzol, L.M.F. J. Braz. Chem. Soc 1993, 4, 179;
  • b) Mahajan, J.R.; Resck, I.S.; Aspesi, G.H. 17th Annual Meeting of SBQ 1994; Abstracts: QO-041.
  • 6. Mahajan, J.R.; Resck, I.S. Synth. Commun 1996, 26, 3809.
  • 7. a) Mahajan, J.R.; Resck, I.S. J. Chem. Soc., Chem. Commun. 1993, 1748;
  • b) Resck, I.S. PhD Thesis 1995; QUI-IE-UNB.
  • 8. Crossland, R.K.; Servis, K.L. J. Org. Chem 1970, 35, 3195.
  • 9. Sonnet, P.E. J. Org. Chem 1974, 39, 3793.
  • 10. Sonnet, P.E. J. Org. Chem. 1980, 45, 154.
  • 11. Schwarz, M.; Graminski, G.F.; Waters, R.M. J. Org. Chem 1986, 51, 260.
  • 12. Olsson, A.-M.; Jonsson, J.A.; Thelin, B.; Liljefors, T. J Chem. Ecol 1983, 9, 375.
  • 13. a) Meinwald, J.; Meinwald, Y.C. J Am. Chem Soc. 1966, 88, 1305;
  • b) Meinwald, J.; Meinwald, Y. C.; Wheeler, J.W.; Eisner, T. Science 1966, 151, 583.
  • 14. Mahajan, J.R.; Resck, I.S.; Braz-Filho, R.; Carvalho, M.G. 5th Meeting of NMR Users (V-AUREMN), Angra dos Reis-RJ, 1995; Abstracts: p 38; , pp 123-132.

Publication Dates

  • Publication in this collection
    01 Dec 2010
  • Date of issue
    1997

History

  • Received
    28 Aug 1996
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