Synthesis of Pheromones: Highlights from 2002-2004

Current Organic Chemistry, 2009, 13, 299-338 299 Synthesis of Pheromones: Highlights from 2002-2004

P. H. G. Zarbin1,*, J. A. F. P. Villar1, I. Marchi1, J. Bergmann2 and A. R. M. Oliveira1

1Departamento de Química, Universidade Federal do Paraná, CP 19081, 81531-990, Curitiba-PR, Brazil 2Instituto de Química, Pontificia Universidad Católica de Valparaíso, Avenida Brasil 2950, Valparaíso, Chile

Abstract: This review summarizes the synthesis of pheromones published in the triennium 2002-2004. The syntheses of a total of 66 pheromone compounds (65 from insects, 1 from a crustacean species), belonging to 9 different structural cate- gories, are presented in schemes. New methodologies, but also well-known reactions have been employed to achieve the (in many cases stereoselective) synthesis of the compounds.

1. INTRODUCTION The chemical structures of pheromones identified so far are diverse and their complexity ranges from simple n- Since its very beginnings in the mid 19th century, or- alkanes to highly complex molecules bearing (multiple) cy- ganic chemistry has made advances unimaginable to the clic substructures, double or triple bonds, heteroatoms, early pioneers of the field. Among the experimental key and/or (multiple) stereogenic centers. In many cases, only techniques contributing to these advances are chromatogra- one stereoisomer or a defined mixture of stereoisomers is phy, which made possible the separation of complex mix- biologically active, while the unnatural isomers or a different tures, and spectroscopic (UV, IR, NMR) and mass spectro- ratio of isomers may be inactive or even inhibit the response metric methods, giving organic chemists powerful tools for to the natural compounds. Against this background, methods the structure determination of organic compounds. This, in are required which lead in high yields and with high stereo- turn, stimulated research in organic synthesis, as products selectivity to the desired compounds. Pheromone syntheses and by-products of reactions could be easily isolated and published over the last few decades have been reviewed re- characterized. As once stated by Meinwald, “Organic chem- peatedly. The most comprehensive reviews are probably istry blossomed into a self-contained, inward-looking sci- those written by Mori in 1981 and 1992 [2, 3]. Other ac- ence, bringing order and understanding to the synthesis and counts, relating pheromone synthesis to specific topics [4-6] reactions of millions of compounds” [1]. This order and un- and a partial, nevertheless impressive update [7] were pub- derstanding allowed the development of countless reactions lished by the same author. Most recently, and reflecting a of carbon-carbon bond formation or modification of func- growing branch in organic synthesis, the application of bio- tional groups, applicable to all classes of organic molecules, catalysis to the synthesis of pheromones has been reviewed which would later eventually be modified or improved, e.g. [8]. in terms of scope, yields, reaction conditions, or stereochemical selectivities. Research in chemical communication In this article, we review the syntheses of pheromones has been profiting from these decade-lasting and ongoing published in the triennium 2002-2004. The aim is to provide efforts, as the synthesis of pheromones is of great importance a comprehensive overview of the syntheses, and we sin- in the process of identifying these chemical messengers. cerely apologize to the authors of those articles which may Moreover, a sort of mutualism has been evolving, as many have escaped our attention. The presentation of the syntheses new synthetic methods have been developped with the ex- is done according to the compound class of the respective plicit aim to improve the synthetic route towards a phero- target compound, adopting the style established by Mori [3]. mone. 2. SYNTHESIS OF ALKANES AS PHEROMONES Pheromones are compounds which are produced and lib- erated by an individual, provocing a behavioural or physio- 2.1. 5,9-Dimethylpentadecane (1) logical response in another individual of the same species. The coffee leaf miner, Leucoptera coffeella, is an eco- As pheromones are usually produced in minute amounts, nomically important pest of coffee trees in Brazil. It has been thus preventing crystallographic or extensive NMR experi- demonstrated by Francke and co-workers [9] that the main ments, their independent synthesis is required to confirm the component of the female-produced sex pheromone of this identification and to establish the absolute configuration in species is 5,9-dimethylpentadecane (1), however, the stereo- case of chiral compounds. Furthermore, chemical synthesis chemistry of the natural pheromone remains unknown. of pheromones provides the amounts necessary for the evaluation of their biological activity in the laboratory or in Moreira and Corrêa [10] described an enantioselective the field. synthesis of three stereoisomers of 1, from commercial isopulegol and synthetic neo-isopulegol [11, 12] (Scheme 1). Zarbin et al. [13] described a straightforward synthesis of *Address correspondence to this author at the Departamento de Química, racemic 1 employing an unsymmetrical double Wittig olefi- Universidade Federal do Paraná, CP 19081, 81531-990, Curitiba-PR, Brazil; Tel: +55 41 33613174; Fax: +55 41 33613186; nation as the key reaction to build the carbon skeleton of the E-mail: [email protected]

1) B2H6 1) NaH, BnBr, THF, 83% OH O 2) H2O2, NaOH, OH 2) PCC, CH2Cl2, 93% H O THF, 0 °C, 84% H 3) m-CPBA/NaHCO , 75% OH 3 (-)- isopulegol OBn

1) MeOH, H+(cat), 93% OTs 2) TsCl, Py, 72% n-BuMgBr, Li2CuCl4 3) LiAIH , THF 4 THF, -78 oC, 90% 4) TsCl, Py, 93% OBn OBn

1) H , Pd/C, MeOH, 73% 2 n-PrMgBr, Li2CuCl4

2) MsCl, Py, CH2Cl2, 91% o THF, -78 C, 90%

OMs (5S,9S) - 1

n-BuMgBr, From (+)-neoisopulegol Li2CuCl4 similarly OTs OBn

(5R,9S) - 1 OBn

EtMgBr,

Li2CuCl4 OBn

Scheme 1. (5S,9R) - 1

2.1 equiv PPh3, DMF, 92% Br Br BrPh3P PPh3Br 1) 1.1 equiv n-BuLi, - 90 oC 2) 1 equiv 2-octanone, - 90 oC to rt.

3) 1.1 equiv n-BuLi, -90 oC 4) 1 equiv 2-hexanone, -90 oC to rt., 64%

H2, Pd/C, hexane, 93% 1 54% overall yield Scheme 2. molecule. The bis-phosphonium salt obtained from 1,3- 2.2. (S)-9-Methylnonadecane (2) and meso-13,23- dibromopropane and triphenylphosphine, was reacted con- dimethylpentatriacontane (3) secutively with the ketones 2-octanone and 2-hexanone, af- (S)-9-Methylnonadecane (2) is a sex pheromone compo- fording the asymmetric diene, which was readily hydrogenated over Pd/C, furnishing 1 in 54% overall yield (Scheme nent of the cotton leafworm Alabama argillacea [14], and meso-13,23-dimethylpentatriacontane (3), is the sex phero- 2). Synthetic 1 showed high biological activity when tested mone of the tse tse fly Glossina pallidipes [14]. in field experiments. Synthesis of Pheromones Current Organic Chemistry, 2009, Vol. 13, No. 4 301

H O O H H Ref. [16] CBr4, PPh3, CH2Cl2, 78% H H H H H HO Br O OH O 1) m-CPBA, MgSO4, CH2Cl2 1) NaOEt, NaBH4, EtOH, 77%

2) PTSA, EtOH, 59% overall 2) H2, Pd/C, EtOAc, 83% H Br

O 1) PCC, CH2Cl2, 78% HO + - O 2) [C7H15PPh3] I , n-BuLi, o THF, -78 C, 98% A

1) DIBAL-H, toluene, -78oC, 86% O ( )8 ( )6 + - 2) [C2H5PPh3] I , n-BuLi, THF, O -78oC, 92% 3) H2, Pd/C, EtOAc, 95% 2

1) PCC, CH2Cl2, 78% A ( )7 O + - 2) [C9H19PPh3] I , n-BuLi, THF, -78oC, 89% 3) DIBAL-H, toluene, -78 oC, 80% B

1) TBDPSCl, imidazole, DMAP, DMF, 81% 1) TBAF, THF, 94% A TBDPSO ( ) ( ) o 3 4 2) DIBAL-H, toluene, -78 C, 80% 2) I2, PPh3, imidazole, CH3CN, + - o 3) [C6H13PPh3] I , n-BuLi, Et2O, 0 C to rt. 87% o THF, -78 C, 89% 3) PPh3, toluene, reflux, 80%

1) n-BuLi, THF, B, -78oC

IPh3P ( )4 2) H2, Pd/C, 99%

( )10 ( )10

3 Scheme 3.

Lamers et al. [15] reported the synthesis of these two [20] described the synthesis of a mixture of all isomers of 4 pheromones starting from the readily available (+)- in 6 steps, starting from hepta-1,6-diene. Pure (R,R)-4 was aromadendrene via the chiral intermediate A [16] (Scheme synthesized by hydrolytic kinetic resolution of the bisepox- 3). ide obtained from hepta-1,6-diene using 1.4 % equiv. of [(R,R)-(salen)Co(III)(OAc)]-Z complex (Fig. 1), followed by 2.3. 7,11-Dimethylheptadecane (4) a Grignard reaction and methylation (Scheme 4). The hydrocarbons 7-methylheptadecane and 7,11- dimethylheptadecane (4) have been identified as constituents 3. SYNTHESIS OF ALKENES AS PHEROMONES of the female-produced sex pheromone of the spring hem- 3.1. (6Z,9Z)-Heneicosa-6,9-diene (5), (3Z,6Z,9Z)- lock looper (Lambdina athasaria) and the pitch pine looper heneicosa-3,6,9-triene (6), and heneicosane (7) (L. pellucidaria) [17, 18]. Subsequently, bioassays con- firmed that (S)-7-methylheptadecane and meso-4, that is (6Z,9Z)-Heneicosa-6,9-diene (5), (3Z,6Z,9Z)-heneicosa- (7S,11R), are the bioactive stereoisomers [19]. Chow et al. 3,6,9-triene (6), and heneicosane (7), have been identified as 302 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.

1) n-C5H11MgBr, CuI, OO O O m-CPBA, CH2Cl2 Et2O ( ) 5 ( )5 2) Jones Reagent.

1) MeMgI, Et2O ( )4 H2, Pd/C ( )5 ( )5 ( )5 2) DMSO racemic and meso-4

OH OOO OH + OO1) (R,R)-Z, H2O OH OH + HO OH

1) n-C5H11MgBr, CuI OMs OMs OO Me2CuLi, ( )5 ( )5 ( )5 ( ) 2) MsCl, Et3N 5 Et2O (R,R)-4 Scheme 4.

H H H H N H2O N N H2O N Co Co

tBu O O tBu tBu O O tBu OAc OAc

tBu tBu tBu tBu

(R,R)-Z (S,S)-Z Fig. (1).

O NH O O O SOCl , 50oC 2 R N R OH R Cl benzene, 24h CHCl , Py, 16h O 3

1) n-C3H7MgCl, CeCl3, TsHN THF, -78oC, 1.5 h O N TsNH-NH2 ( )4 ( )7

R EtOH, rt., 24h R 2) 10% AcOH ( )4

( )16

5 1) DIBAL-H, CH2Cl2 0oC, 30 min 6 2) 3N NaOH

Scheme 5. pheromone components of Achaea janata, a destructive oli- responding morpholine amides. The resulting propyl ketones gophagus insect for castor crops, especially when young were reduced via their tosylhydrazones (Scheme 5). crops are attacked. 3.2. (9E,11Z)-Hexadeca-9,11-dienal (8) Badioli et al. [21] described the synthesis of these three hydrocarbons from linoleic, linolenic, and stearic acid, re- (9E,11Z)-Hexadeca-9,11-dienal (8) has been identified as spectively, by addition of organocerium reagents to the cor- a female-produced sex pheromone of the pecan nut case- bearer (Acrobasis nuxvorella) [22]. Synthesis of Pheromones Current Organic Chemistry, 2009, Vol. 13, No. 4 303

H O + basic Alumina, MeC(OEt)3, H O OEt benzene OH

o 1) LiAlH4, Et2O, 0 C 1) BrMg(CH ) OTHP, CuI OEt 2 7 OAc 2) Ac2O, Py 2) PTSA, MeOH O

1) tetracyanoetylene, THF O OH

2) P2O5, DMSO, then Et3N H (E,Z:E,E 2:1) 8

OH O H 1) n-BuLi, Et2O MeC(OEt) , H+ 3 OEt 2) acrolein

o 1) BrMg(CH ) OTHP, CuI, -78oC 1) LiAlH4, Et2O, 0 C 2 5 OTs 2) PTSA, MeOH 2) TsCl, Et3N 3) recrystallization

O 1) Zn, C2H4Br2, LiCuBr2 OH 2) P2O5, DMSO, then Et3N H >99% E 8

Scheme 6.

1) Ref. [25] HO Br THPO 2) 2-propyne-1-ol/LiNH , fl. NH OH 2 3 1) LiAlH4, Et2O, rt. [n-BuPPh3]+Br- O THPO NaHMDS, THF, -20oC 2) (COCl)2, DMSO H 3) Et N, CH Cl , -78oC 3 2 2 1) PTSA, MeOH, rt. Separation of (E,E)-isomer by

THPO Diels-Alder reaction with 2) (COCl)2, DMSO o tetracyanoethylene 3) Et3N, CH2Cl2, -78 C H

O 9 Scheme 7.

Two alternative syntheses were described by Passaro and 4. SYNTHESIS OF EPOXY PHEROMONES Webster [23]. The key steps in both sequences is an or- 4.1. (6Z,9Z,11S,12S)-trans-11,12-Epoxyheneicosa-6,9- thoester Claisen rearrangement (Scheme 6). diene (10) (Posticlure) 3.3. (8E,10Z)-8,10-Tetradecadienal (9) Wakamura et al. [26] identified posticlure [(6Z,9Z, Francke et al. described the synthesis of (8E,10Z)-8,10- 11S,12S)-trans-11,12-epoxyheneicosa-6,9-diene, 10] as the tetradecadienal (9), the female produced sex pheromone of female-produced pheromone of the tussock moth Orgyia the horse-chestnut leafminer (Cameraria ohridella) [24]. postica. Fernandes and Kumar [27] described a highly enan- The synthesis of 9 was carried out in 30% overall yield, tioselective synthesis of (+)- and (-)-posticlure employing starting from 7-bromoheptanol. The (8E) configuration was the Sharpless asymmetric dihydroxylation of olefin A or the achieved by stereoselective reduction of an acetylene, while regio- and stereoselective mono-dihydroxylation of the trans the (10Z) configuration results from a stereoselective Wittig olefin bond of the (Z,Z,E)-triene B to obtain the enantiomeri- reaction (Scheme 7). cally pure diols C and D, which were transformed into (+)- 304 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.

OH O

(DHQ) -PHAL or (DHQD) -PHAL, 2 2 ( )8 OEt OsO4, MeSO2NH2, K3Fe(CN)6, O O OH Ph3P=CHCO2Et, K CO , t-BuOH/H O [1:1], 2 3 2 or THF, rt., 12 h, 86% ( )8 H ( )8 OEt OH O o A 24 h, 0 C, 94% ( )8 OEt

OH O 1) (COCl) , DMSO, CH Cl , 1) 2,2-DMP, (CH3)2CO, 2 2 2 O o o PTSA, rt., 8 h, 99% ( )8 OH Et3N, -78 to -60 C ( )8 ( )4

O O 2) [(Z)-C H CH=CHCH CH P+Ph ]I-, 2) LiAlH4, Et2O, 5 11 2 2 3 0oC to rt., overnight, 97% n-BuLi, THF, -80oC, 8 h, 76%

OH OH 3N HCl, MeOH, rt., 12 h, 90% ( ) ( ) ( ) ( ) 8 4 or 8 4 OH OH C D

O o 1) DIBAL-H, Et2O, 0 C, 0.5 h, 90% ( ) ( ) ( ) 8 OEt 8 4 2) PCC, CH Cl , rt., 8 h A 2 2 B + - 3) [(Z)-C5H11CH=CHCH2CH2P Ph3]I , LiHMDS, THF, -80oC, 8 h, 74%

(DHQ)2-PHAL, OsO4, MeSO2NH2, OH K3Fe(CN)6, K2CO3, t-BuOH/H2O [1:1], o B 10 h, 0 C, 78% ( )8 ( )4 OH C

(DHQD)2-PHAL, OsO4, MeSO2NH2, OH K3Fe(CN)6, K2CO3, t-BuOH/H2O [1:1], o 10 h, 0 C, 79% ( )8 ( )4 B OH D

1) CH C(OMe) , PTSA (cat), 3 3 OAc Br CH2Cl2, rt, 30 min ( ) ( ) C or D ( )8 ( )4 + 8 4 2) CH COBr, CH Cl , rt., 4 h Br OAc 3 2 2

K CO , MeOH, rt., 4 h, 2 3 H H ( )4 86 - 88% overall ( )4 or ( ) H ( )8 H 8 O O (-) - 10 (+) - 10 Scheme 8. and (-)-10 via the respective acetoxybromides in a one-pot female-produced sex pheromone of the Satin moth, Leucoma reaction (Scheme 8). salicis [28]. Muto and Mori [29] employed the lipase PS- C(Amano)-catalyzed asymmetric acetylation of (±)-4-(tert- 4.2. (3Z)-cis-6,7-cis-9,10-Diepoxyheneicos-3-ene (11) (leu- butyldiphenylsilyloxy)-cis-2,3-epoxybutan-1-ol, which af- comalure) forded the (2R,3S)-epoxy alcohol A and the (2S,3R)- Gries et al. identified leucomalure [(3Z)-cis-6,7-cis-9,10- epoxyacetate B as optically active building blocks to prepare diepoxyheneicos-3-ene, 11] as the major component of the all isomers of 11 (Scheme 9). Synthesis of Pheromones Current Organic Chemistry, 2009, Vol. 13, No. 4 305

Lipase PS-C, 1) NaH, TBDPSCl, THF, 92% O HO OH TBDPSO OH CH2=CHOAc, Et2O

2) m-CPBA, CH2Cl2, 94% O O TBDPSO OH TBDPSO OAc +

(2S,3R)-B (2R,3S)-A 48%, 98.1% e.e. O 49%, 99.5% e.e. TBDPSO OH K2CO3, MeOH, 99% (2S,3R)-A

98.1% e.e.

n-BuLi, Tf O; then Me(H C) C CLi O 2 2 10 O ( )10 TBDPSO OH THF, HMPA, 77% TBDPSO

(2R,3S)-A

- + O O O O 1) H2, Pd/CaCO3 Pb2 , cyclohexane TBDPSO + TBDPSO ( )10 ( )10

2) m-CPBA, CH2Cl2; then MPLC (2S,3R,5R,6S)-C 58% separation. (2S,3R,5S,6R)-C 23% 1) TBAF, THF, 81%

2) n-BuLi, Tf O; then Me(H2C)10C CLi 2 THF, HMPA, 77%

- + O O H2, Pd/CaCO3 Pb2 , Et O O cyclohexane Et ( )10 ( ) 10 (3Z,6S,7R,9S,10R)-11

Similarly O O O O

TBDPSO Et ( )10 ( )10 (3Z,6S,7R,9R,10S)-11 (2S,3R,5R,6S)-C O O

Et ( )10 Similarly O TBDPSO OH (3Z,6R,7S,9R,10S)-11

(2S,3R)-A O O

Et ( )10

(3Z,6R,7S,9S,10R)-11 Scheme 9.

All four isomers of 11 have also been synthesized by 4.3. (6Z)-cis-9,10-Epoxyheneicos-6-ene (12) and (6Z)-cis- Wimalaratne and Slessor, using D-xylose as the optically 9,10-epoxyeicos-6-ene (13) pure starting material [30]. The epoxy alcohol A was trans- The pure enantiomers of epoxide A used in Mori’s syn- formed to chain-elongated epoxy alcohols B and C, respec- thesis of 11 [29] (Scheme 9) were also the key intermediates tively, which were subsequently epoxidized by the method for the synthesis of the enantiomers of (6Z)-cis-9,10- of Sharpless and finally alkenylated to give the pure isomers epoxyheneicos-6-ene (12) and (6Z)-cis-9,10-epoxyeicos-6- of 11 (Scheme 10). ene (13) [31] (Scheme 11). 306 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.

OH SEt OH O + 1) LiAlH4 HO 1) EtSH/H SEt CHO HO O O OH O 2) TBDMSCl OH 2) acetone/I2 . O 3) HgO/BF Et O 3) t-BuOK 3 2

OTBDMS OH OH + - 1) [Me(CH2)8PPh3] Br CHO 1) TsCl ( ) O HO 10 ( )10 2) K2CO3 O O 2) H2, Pd/C, OH 3) TFA, aq. THF A A

1) TsCl 1) TBDMSCl 2)TBDMSOCH CC-Li+, - + 2 2) TBDMSOCH2CC Li , BF3. Et2O BF3 .Et2O 3)K2CO3 3) TsCl OTBDMS O TBDMSO ( )10 TBDMSO ( )10 OTs

1) TBAF 1) TBAF 2) P2-Ni, H2 2) P2-Ni, H2 O O

OH HO ( )10 ( )10

B C B

1) (+)-(L)-DET 1) (-)-(D)-DET 2) TsCl 2) TsCl

3) (C4H7)2CuLi 3) (C4H7)2CuLi

O O O O

( ) 10 Et ( )10 Et (Z)-3-(6S,7R,9S,10R)-11 (Z)-3-(6R,7S,9S,10R)-11 C

1) (+)-(L)-DET 1) (-)-(D)-DET

2) TsCl 2) TsCl 3) (C H ) CuLi 4 7 2 3) (C4H7)2CuLi OO OO

Et ( )10 Et ( )10

(Z)-3-(6R,7S,9R,10S)-11 (Z)-3-(6S,7R,9R,10S)-11

Scheme 10.

5. SYNTHESIS OF NON-ISOPRENOIDAL PHERO- cies [32, 33]. Baraldi et al. [34] reported the enantioselective MONE ALCOHOLS AND THEIR ESTERS synthesis of (R)- and (S)-14 starting from isovaleryl chloride. 5.1. 2-Methyl-4-octanol (14) The key step of this synthetic route is the asymmetric reduction of ethyl 5-methyl-3-oxohexanoate with Saccharo- 2-Methyl-4-octanol (14) has been described as a compo- myces cerevisiae to the corresponding hydroxyester (S)-A in nent of the aggregation pheromones of several weevil spe- high enantiomeric excess (Scheme 12). The (S) isomer was Synthesis of Pheromones Current Organic Chemistry, 2009, Vol. 13, No. 4 307

O O n-BuLi, Tf O LiC C(CH2)4Me, THF TBDPSO OH 2 TBDPSO OTf

A HMPA, 74% overall

4 O O ( ) H , Pd/CaCO -Pb + 1) TBAF, THF, 99% 2 3 2 TBDPSO TBDPSO ( )4 cyclohexane, quant. 2) TsCl, Py, 77% O

(n-C10H21)2CuLi, Et2O, 80% ( )10 ( )4 O (9S,10R)-12 TsO ( )4 O (n-C9H19)2CuLi, Et2O, 80%

( )9 ( )4

O (9S,10R)-13

Similarly O ( )10 ( )4 TBDPSO OH (9R,10S)-12 A O

( )9 ( )4 (9R,10S)-13 Scheme 11.

O OH LiCH CO Et, 85% O S. cerevisiae 2 2 CO Et CO Et 2 Cl 2 allyl alcohol (S) - A 1) p-NO2C6H6CO2H 50%, 99% e.e. OH Ph3P, DEAD CO2Et

2) NaOH, EtOH (R) - A 70%, 99% e.e.

OH OH 1) LiAlH4, THF, 85% (R) - A or (S) - A or

2) TsCl, Et3N, 80% (R) - 14 (S) - 14 3) EtMgBr, Li2CuCl4, 70% Scheme 12. prepared in five steps and 20% overall yield, while the (R) Scolytus scolytus and S. multistriatus [37-40]. Recently, enantiomer was obtained in six steps and 14% overall yield. (3S,4S)-15 was tentatively identified as the main component The key step of the synthesis of (R)-14 described by of the aggregation pheromone of the almond bark beetle, Dhotare et al. [35] is the K-selectride reduction of the inter- Scolytus amygdali, along with (3S,4S)-4-methyl-3-hexanol, mediate ketone A obtained from D-mannitol. The reduction which functions as a synergist. Substitution of the pure proceeded with absolute syn selectivity (Scheme 13). (3S,4S) isomer with racemic 4-methyl-3-heptanol in field D-mannitol was also used by Zarbin et al. [36] to obtain tests resulted in a lower trap catch of beetles in the field, (S)-14 by a new and higly enantioselective approach, involv- indicating the possibility that one or more of the unnatural stereoisomers has an inhibitory effect [41]. ing the known (R)-glyceraldehyde acetonide A as key intermediate (8.8% overall yield) (Scheme 14). Zada et al. [42] described the synthesis of all four stereoisomers of 15. Key steps included preparation of enan- 5.2. 4-Methylheptan-3-ol (15) tiomerically pure (R)- and (S)-4-methyl-3-heptanone (A) by the SAMP/RAMP method, reduction to the corresponding (3S,4S)-4-Methylheptan-3-ol [(3S,4S)-15] is the major alcohols, and stereospecific transesterification with vinyl component of the aggregation pheromone of the bark beetles acetate by lipase AK catalysis (Scheme 15). In field tests, 308 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.

Steps 1) n-BuMgBr, THF K-selectride, OO D-Mannitol OO THF, -78oC

2) PCC, CH2Cl2 CHO O A

OO OH 1) NaH, BnBr, THF 1) NaIO4, aq. MeCN HO

2) NaH, DMSO, OH 2) TFA, H2O, CH2Cl2 OBn [Me CHPPh +]Br-, THF 2 3 H2, Pd/C, EtOH OH

OBn (R) - 14 Scheme 13.

MeO OMe 1) [n-C H PPh +Br]-, OH OH 3 7 3 1) SnCl2, , 55% O n-BuLi, THF, 88% HO O H OH 2) NaIO4, NaHCO3, CH2Cl2, 61% OH OH O 2) H2, Pd/CaCO3, hexane, 81% A 1) acidic DowexÆ W , 50 OH O OH i-C3H7MgBr, H2O, 79% O TsO CuI, THF, 78% 2) TsCl, Py, 60% (S)-14

8.8% overall yield; 99.5% e.e. Scheme 14.

O o Ref. 43 LiAlH4, Et2O, 25 C Lipase AK, vinyl acetate

O (S) - A OH

KOH, MeOH +

OH OAc OH

(3S,4S)-15 (3R,4S)-15

OH Similarly (3R,4R)-15

O (R) - A OH (3S,4R)-15 Scheme 15. only (3S,4S)-15 attracted beetles in combination with the precursor isolated from some pine sawflies of the genus Gil- synergist (3S,4S)-4-methyl-3-hexanol, whereas the (3R,4S) pinia. The enantiomers of 2-methyl-3-(phenylsulfanyl)pro- and (3R,4R) isomers were inhibitory. panal [(S)-A or (R)-A] were prepared from readily available (S)- and (R)-3-hydroxy-2-methylpropanoic acid methyl ester 5.3. (2S,3R)-3-Methylpentadecan-2-ol (16) and were reacted with dimethylzinc to give the isomers Larsson et al. [44] described the synthesis of (2S,3R)-3- (2S,3S)-B or (2R,3R)-B, respectively, both of high d.e. and e.e. These products were further purified by lipase catalysed methylpentadecan-2-ol [(2S,3R)-16], a putative pheromone Synthesis of Pheromones Current Organic Chemistry, 2009, Vol. 13, No. 4 309

O 1) (PhS) , (n-Bu) P, DMF, 1) DMSO, oxalyl chloride, -78oC O 2 3 OH o o 0 C, rt., 95% 2) DIPEA, CH2Cl2, -78 C HO OMe PhS H PhS

2) LiAlH4, THF, 96% 3) extractive workup with KH2PO4 (R)-A or (S)-A

o CH2Cl2, -78 C, OH OH OH OH TiCl (1.0 equiv), 4 PhS + PhS + PhS + PhS

10 min, Me2Zn (1.0 equiv) 75% 2 steps (2S,3S)-B (2R,3S)-B (2R,3R)-B (2S,3R)-B

From (S) - A 91,5% 7% 1.4% 0.1% From (R) - A 2.9% 0.2% 92% 4.9%

Mixture of the OH OTBDMS stereoisomers CAL-B 9% 1) TBDMSCl, DMF, imidazole, 99% PhS of B obtained O2SPh from (S)-A 2) m-CPBA, CH2Cl2, 88% >1000/1 d.r. >99.9% e.e. 90% yield 1) THF, DMPU, -40oC, n-BuLi (2.1 equiv), PhSO2 OTBDMS up to 0oC, cool to -40oC

2) 1-Iodoundecane (1.2 equiv), THF, up to 20oC (96%)

OH 1) 10% Na/Hg, MeOH, Na2HPO4, rt., 94%

2) i) TBAF, THF, reflux

ii) acetylchloride, Py, CH2Cl2, 84% 16 3) i) Raney Ni, EtOH, H2. ii) KOH/MeOH, rt., 82%

Scheme 16. acylation to give the enantiomerically and diastereomerically 5.5. (2S,3R,7RS)-3,7-Dimethyltridec-2-yl acetate (21) and highly pure enantiomers (>99% d.e., >99.9% e.e.). Pure propanoate (22) (2S,3S)-B was transformed to (2S,3R)-16 in 54% yield over 3,7-Dimethyltridec-2-yl acetate (21) and propanoate (22) eight steps (Scheme 16). are sex attractants of the sawfly Diprion pini [48]. 5.4. 3-Methylpentadecan-2-ol (16), 3,7-dimethyltridecan- Bekish et al. [50] described a synthesis of a mixture of 2-ol (17), 3,7,11-trimethyltridecan-2-ol (18), 3,7,9- the diastereomers (2S,3R,7S)- and (2S,3R,7R)-21, as well as trimethyltridecan-2-ol (19), and 3,7-dimethyltetradecan- (2S,3R,7S)- and (2S,3R,7R)-22 by cyclopropanation of the 2-ol (20) ethoxycarbonyl group in O-THP protected ethyl (S)-lactate with ethylmagnesium bromide in the presence of tita- Hedenström et al. [45] reported the synthesis of precur- nium(IV) isopropoxide, and subsequent C2–C3 ring opening sors of the sex pheromones of females of pine sawfly species of the resulting cyclopropanol (Scheme 18). The resulting [46-49]. The key reaction sequence in the syntheses was the (S) configured bromoalkenol A (stereoisomeric purity 98%) ring opening of either cis- or racemic trans-2,3-epoxybutane was chain-elongated and hydrogenated. The (3R) configura- using a higher order cyanocuprate as nucleophile, obtained tion was established by esterification with phthalic anhydride from iodides or chlorides E – I, followed by a highly effi- followed by salt formation with pure (S)-1-phenylethylamine cient lipase catalysed stereoselective acylation of the result- and several recrystallisations of this salt to give the alcohol ing 3-methylalkan-2-ols (Scheme 17). with 92 % e.e. at C-3. 310 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.

1) (Ph P) NiCl , benzene 1) t-BuLi, THF 3 2 2

2) MeMgBr O O 3) add 2-hexyl-4,5-dihydrofuran, 2) 1-iodohexane 80 oC 5 h

Pd/C, H2 MeOH OH OH

1) Na(s), EtOH O PPh3, Br2, CH2Cl2 2) CH (CO Et) ROH 2 2 2 RBr R OH 3) KOH, EtOH R = 1-hexyl S or R 4) 180 - 200 oC R = 2-hexyl

R = 1-(3-methylpentyl)

B R = 1-hexyl S or R LiAlH4, Et2O R OH C R = 2-hexyl D R = 1-(3-methylpentyl)

1) Li, hexane PPh3, CCl4 or A, B, C, or D R X

R' 2) add to MeCu(CN)Li, PPh3, I2, imidazole, Et O, -78 oC THF/MeCN 2 3) add cis- or racemic trans-epoxybutane E R = 1-pentyl, R' = CH3, X = I

F R = 1-hexyl, R' = CH3, X = I, S or R G R = 2-hexyl, R' = CH , X = Cl or I 3 H R = 1-(3-methylpentyl), R' = CH3, X = I and I - 1-Chlorododecane

OCOR'' * R'' = Me, Pr, or Bu R OH lipase, vinyl ester, * heptane, 3 Å. R' R threo-(2R,3R) or erythro-(2R,3S) esters R' + threo or erythro 16-20 OH

* 17 R = 1-pentyl, R' = CH3, R * 18 R = 1-hexyl, R' = CH , S or R 3 R' 19 R = 2-hexyl, R' = CH3, threo-(2S,3S) or erythro-(2S,3R)

20 R = 1-(3-methylpentyl), R' = CH3, 16 R = 1-heptyl, R' = H

Scheme 17.

5.6. 3,7-Dimethyltridec-2-yl propanoate (23) quasi isomers were mixed and subjected to reactions, and finally demixed by fluorous silica chromatography, making Dandapani et al. described a synthesis of all 16 stereoi- use of the different fluorine tag of each isomer. In the first somers of 3,7-dimethyltridec-2-yl propanoate (23), the sex step of the reaction sequence, each of the cuasi isomer in the pheromone of the pine sawfly Microdiprion pallipes, by a mixture M-1 was reduced, partially oxidized, then the mix- fluorous mixture-synthesis approach [51]. Each of the four ture was split and each part chain-elongated using the chiral stereoisomers of 2-methyl-1,3-butanediol was marked sepa- building block (S)-E or (R)-E. Each mixture obtained [M-2 rately with a different fluorine-containing group, then the (R) and M-2 (S)] was split again and chain-elongated sepa- Synthesis of Pheromones Current Organic Chemistry, 2009, Vol. 13, No. 4 311

1) DHP, PPTS (5 mol %), OTHP OH OH 1) MsCl, Et N, Et O. CH2Cl2, 89% 3 2 Br CO2Et 2) MgBr , CHCl /Et O 2) EtMgBr, Ti(Oi-Pr)4, OH 2 3 2 59% (3 steps) Et2O/THF A OTHP 1) DHP, PPTS (5 mol %), CH Cl , 96% 2 2 1) MeOH, PPTS (5 mol %.), 95%

2) 3-methylnonylmagnesium bromide, . 2) NaBH4, NiCl2.6H2O, MeOH, 86% CuI (5 mol %), 91%

OH OH 1) phthalic anhydride, Et3N, benzene

2) (S)-(-)-1-phenylethylamine, acetone 3) four recrystallizations from acetone 4) KOH, MeOH, 33% overall yield

CH3COCl or C2H5COCl, OR Et3N, Et2O, 85 - 90%

(2S, 3R, 7RS)-21 R=COMe (2S, 3R, 7RS)-22 R=COEt Scheme 18. rately with the same reagent (S)-E or (R)-E, giving rise to pheromone found in the ants Crematogaster castanea and C. four mixtures M-3. After hydrogenation, each mixture was liengmei [53, 54]. (R)-2-Dodecanol (25) is a component of separated by HPLC and the fluorine-containing group was the hind leg tibial gland secretion of worker ants of C. au- removed to give the target compounds (Scheme 19). berti [55]. (R)-2-Methyl-4-heptanol (26) and (R)-2-methyl-4- octanol (14) were identified as the male-produced aggrega- 5.7. (R)-2-Methyl-4-octanol (14), (R)- and (S)-3-octanol tion pheromones of the West Indian sugarcane weevils (24), (R)-2-dodecanol (25), and (R)-2-methyl-4-heptanol Metamasius hemipterus [32, 56]. Scheme 20 shows the syn- (26) thesis of the optically active insect pheromones 14 and 24-26 described by Cho and Kim, starting from enantiomerically (R)-3-Octanol [(R)-24] is the sex attractant pheromone of pure -hydroxy sulfides [57]. The -hydroxy sulfides were the ant Myrmica scabrinodis [52] while (S)-24 is an alarm

OH OH C6H4-p-O(CH2)3Rf 1) TMSCl, ET3N O O 2) TMSOTf,

Rf(CH2)3OC6H6CHO (A-D), 4 isomers 3) Mix in equimolar amts A: Rf = C4F9 (S,S)

B: Rf = C6F13 (R,S) M-1 (4 quasi isomers) C: Rf = C7F15 (S,R)

OFPAB D: Rf = C8F17 (R,R) Ph O (S) - E N S

OTBS N OTBS NaHMDS O N N 1) DIBAL-H M-2 (R), 90% (S) - E M-1 Ph O 2) Dess - OFPAB N S (R) - E N OTBS Martin O N periodinane OTBS N NaHMDS (R) - E M-2 (S), 89% 312 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.

Scheme 19. Contd…. 1) TBAF OFPAB OFPAB (S) - E 2) Dess-Martin OTBS periodinane NaHMDS 1) TBAF M-3 (R,R), 75% 3) CH2=PPh3 M-2 (R) M-4 (R,R), 77% 4) NH=NH

2) Dess - OFPAB OFPAB (R) - E Martin OTBS periodinane NaHMDS

M-3 (R,S), 75% M-4 (R,S), 77%

OFPAB OFPAB (S) - E OTBS NaHMDS 1) TBAF M-3 (S,R), 80% M-4 (S,R), 77% M-2 (S)

2) Dess - OFPAB (R) - E OFPAB Martin periodinane OTBS NaHMDS M-3 (S,S), 80% M-4 (S,S), 77% O 1) HPLC separation O M-4 (R,R)

2) Pd/C, H2, 97% 3) EtCOCl (8 equiv.) Then PS-trisamine (97%) 23 - 4 individual isomers M-4 (R,S) Similarly M-4 (S,R) 23 - 12 individual isomers

M-4 (S,S)

Scheme 19. prepared by enantioselective reduction of the corresponding 5.9. (-)-(R)- and (+)-(S)-10-Methyldodecyl acetate (28) -keto sulfides, catalyzed by oxazaborolidine (R)- or (S)-X (R)- and (S)-10-Methyldodecyl acetate (28) are compo- with 74 – 81% e.e. Recrystallization of the acylated - hydroxy sulfides in appropriate solvents increased the enan- nents of the pheromone of the lesser tea tortrix moth, Adoxo- tiomeric purity to 96 – 99% e.e. The sulfides were deacy- phes spp. [60, 61]. Chow and Kitching [59] described the lated, oxidized to the sulfoxides, alkylated if necessary, and synthesis of both enantiomers. Benzyl ether A was epoxi- reduced with Raney-Ni to furnish the target compounds. dized with m-CPBA and the enantiomers of the resulting epoxide B were kinetically resolved by stirring with 0.5 5.8. (-)-(2R,6Z)-Undec-6-en-2-ol (27) (nostrenol) mol% of (R,R)-Z and 0.55 mol equiv. of H2O at room temperature (22°C) for ca. 24 h, giving (R)-epoxide B and (S)- Nostrenol [(2R,6Z)-undec-6-en-2-ol, 27] was identified diol C, which were straightforwardly converted to (R)-28 from thoracic glands of the ant-lion species Euroleon nostras and (S)-28, respectively (Scheme 22). and Grocus bore [58]. Chow and Kitching [59] described the synthesis of this and other insect pheromones (sections 5.9., 5.10. 6-Acetoxy-19-methylnonacosane (29) and 7-acetoxy- 5.11., 5.12., and 6.4.) by hydrolytic kinetic resolution (HKR) 15-methylnonacosane (30) of functionalised epoxides, using (salen)Co(OAc) complexes (R,R)-Z and (S,S)-Z (Fig. 1), providing enantiomerically In 1993, Pomonis et al. reported the identification of six- enriched epoxides and diols. The synthesis of 27 started from teen compounds in a pheromonally active HPLC fraction undec-1-en-6-yne (A), which was epoxidised with m- extracted from the females of the screw-worm fly Cochlio- chloroperbenzoic acid in dichloromethane [59]. HKR of the myia hominivorax [62]. In 2002, Furukawa et al. synthesized resulting epoxide furnished the (S)-epoxide B and diol C. five possible pheromone candidates [63], and a bioassay of (S)-B was further transformed to 27 (Scheme 21) these five compounds showed activity for 6-acetoxy-19- Synthesis of Pheromones Current Organic Chemistry, 2009, Vol. 13, No. 4 313

C m-CPBA, CH Cl , O OH 2 2 rt. 95%. S-p-tolyl (R) or (S)-MeCBS (X, 0.1 equiv.) S-p-tolyl R R O R = n-C H , 74% e.e. N-ethyl-N-isopropylaniline- 5 11 R = n-C5H11 R = i -Bu, 81% e.e. Ar O O borane complex (Y, 1.0 equiv.), R = i-Bu R = n-C H , 79% e.e. S-p-tolyl THF, 25oC 98 - 99% 10 21 R R = n-C10H21 C' H 3,5-(NO2)2C6H3COCl, Ph Et TMEDA, CH2Cl2, 97 - 99% N Ph O O N B Ph Pr-i Ar O Me BH3 S-p-tolyl (S) - X (Y) R A, 96% e.e. A R = n-C5H11, 74% e.e. recrystallization B R = i -Bu, 81% e.e. B, 98% e.e. C R = n-C H , 79% e.e. O 10 21 C', 99% e.e. O Ar O 1) 2N, NaOH, OH O 2N, NaOH, MeOH, rt. Ar O O S-p-tolyl R MeOH, rt., 98 - 99% S-p-tolyl R S-p-tolyl R

D R = n-C5H11, 96% e.e. A R = n-C H , 96% e.e. 5 11 2) m-CPBA, CH2Cl2, C' R = n-C10H21 E R = i-Bu, 98% e.e. B R = i-Bu, 98% e.e. rt. 95% F R = n-C10H21, 79% e.e.

OH O n-BuLi(2.8 eq.), R' I, OH O o o S-p-tolyl THF, -78 - 20 C, 72 - 93% R S-p-tolyl R R' D R = n-C5H11, 96% e.e. E R = i-Bu, 98% e.e. G R = n-C5H11, R' = Me H R = i-Bu, R' = Et I R = i-Bu, R' = n-Pr

OH OH

(R)-24 (S)-24 G Raney Ni, MeOH, OH OH ent-G rt., 89 - 92% H (R)-26 (R)-14 I OH

(R)-25 Scheme 20. methylnonacosane (29) and 7-acetoxy-15-methylnonacosane (Scheme 23) were synthesized with high stereochemical pu- (30). rities (more than 90% e.e. at C-6; about 97% e.e. at C-19). Mori et al. described a synthesis of all possible stereoi- The stereoisomers of 30 (Scheme 24) were obtained somers of 29 [64] and 30 [65]. Starting from the enantiomers starting with the pure enantiomers of citronellal. The (R) and of citronellal and oct-1-yn-3-ol, all four stereoisomers of 29 (S) configuration, respectively, was carried through to C-15, 314 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.

( )3

3 0.5% equiv. (S,S)-Z, m-CPBA, CH2Cl2 ( ) O 0.55 equiv. H2O

A 3 ( ) ( )3 OH O + OH

B C

( ) 3 + 3 NaBH4, EtOH ( ) OH 1) DHP, H B

2) Ti(Oi-Pr)4, i-PrMgBr, Et O then H O OH 2 2 3) MeOH, H+ 27 Scheme 21.

OH 1) m-CPBA, CH2Cl2 O ( )7 OBn ( )7 OBn HO ( )7 OBn + A 2) 0.5% equiv (R,R)-Z, B C 0.55 equiv. H2O, rt. 24 h

o 1) O , Me S 1) Me2CuLi, Et2O, 0 C 7 3 2 ( ) OBn ( )7 OAc B

2) MsCl, Et N, 2) K CO , MeOH 3 2 3 (R)-28 o 3) Me2CuLi, Et2O, 0 C 3) Ac2O, Py

1) MsCl, Et3N OH 1) MsCl, Et3N C ( )7 OBn ( )7 OBn

2) K2CO3, MeOH 2) Me CuLi, Et O, 0oC o 2 2 3) Me2CuLi, Et2O, 0 C

1) H2, Pd/C ( )7 OAc

2) Ac2O, Py (S)-28

Scheme 22. while a lipase-catalyzed asymmetric acetylation defined the Similarly, HKR of a stereoisomeric mixture of diepoxide absolute configuration at C-7. C afforded pure (2R,12R)-C, which was transformed to (2S,12S)-32 [59] (Scheme 26). 5.11. (2S,11S)-2,11-Diacetoxytridecane (31) and (2S,12S)- 2,12-diacetoxytridecane (32) 5.12. (1R,7R)-1,7-Dimethylnonyl propanoate (33) (2S,11S)-2,11-Diacetoxytridecane (31) and (2S,12S)- Various isomers of 1,7-dimethylnonyl propanoate (33) exhibit attractancy for males of corn rootworms, with the 2,12-diacetoxytridecane (32) are two of the three active western corn rootworm (Diabrotica virgifera virgifera) and components identified by coupled gas chromatography– the northern corn rootworm (D. barberi) responding strongly electroantennography of extracts from the pheromone glands to the (1R,7R)-isomer [68]. The synthesis of this isomer is of female pea midges (Contarinia pisi) which are serious shown in Scheme 27. The racemic bisepoxide A obtained by pests of commercial peas [67]. The key step in the synthesis m-CPBA epoxidation of 1,8-nonadiene was treated with of diester 31 was the HKR of a stereoisomeric mixture of the 1.0% equiv. of (R,R)-Z and 0.8 equiv. of H2O, providing a diepoxide A affording the epoxi-diol (2R,11S)-B, which was mixture of the (S,S)-bisepoxide, the (S,S)-epoxydiol B and transformed to (2S,11S)-31 [59] (Scheme 25). the (S,S)-tetraol. After column chromatography, epoxydiol B Synthesis of Pheromones Current Organic Chemistry, 2009, Vol. 13, No. 4 315

1) THPO(CH2)7MgBr, Ref. [66] Li CuCl , THF OHC OTs 2 4 ( )9

2) PTSA, MeOH (69%, 2 steps) 1) TsCl, Py OH ( ) ( ) I 9 10 ( )9 ( )10 2) NaI, DMF (77%, 2 steps) (S)-A

Similarly OHC I ( )9 ( )10 (R)-A

OH OH 2.2 eq. n-BuLi, THF/HMPA,

then (S)-A 68% ( )4 ( )4 ( )9 ( )10 (S)-B

1) H , PtO , EtOAc 2 2 OAc (15 min at rt. 85%)

( )9 ( )12 ( )4

2) Ac2O, DMAP, Py, (6S,19S)-29 CH2Cl2 (98%)

OAc

(R)-A + (S)-B ( )9 ( )12 ( )4 (6S,19R)-29

OAc (R)-A + (R)-B ( )9 ( )12 ( )4 (6R,19R)-29

OAc (S)-A + (R)-B ( )9 ( )12 ( )4

(6R,19S)-29

Scheme 23. was transformed to (1R,7R)-33 in nine steps [59] (Scheme (4R,8S) was about 10 times more active than (4R,8R)-35 27). alone. Ismuratov and co-workers [76] described a synthesis of 6. SYNTHESIS OF NON-ISOPRENOIDAL ALDE- 34 and 35 starting from (S)-3,7-dimethyl-1,6-octadiene. The HYDES, KETONES, ACIDS, AND ESTERS AS hydroxyketone B, obtained by ozonolysis of the unsaturated PHEROMONES ketone A followed by reductive workup, was either trans- 6.1. (R)-4-Methylnonan-1-ol (34) and (4R,8RS)-4,8- formed to (R)-34 or (4R,8RS)-35 (Scheme 28). dimethyldecanal (35) 6.2. (E)-2-(4-Methyl-3-pentenylidene)butanedial (36) (- (R)-4-Methylnonan-1-ol (34) was identified as a sex at- acaridial) tractant of the yellow mealworm Tenebrio molitor by Tanaka [69, 70] et al. In 1980, Suzuki identified 4,8-dimethyldecanal -Acaridial [(E)-2-(4-methyl-3-pentenylidene)butanedial, (35) as the aggregation pheromone of the red flour beetle 36] is known as the sex pheromone [78] and aggregation (Tribolium castaneum) and of the confused beetle (Tribolium pheromone [79] of Caloglyphus polyphyllae and as the alarm confusum), notorious pests of various stored products [71, pheromone [80] of Tyrophagus longior. 72] Mori and co-workers [73, 74] established the absolute Shimizu et al. [81] described the synthesis of 36 in five configuration of natural 35 as (4R,8R). Suzuki et al. [75] steps from 1,2,4-butanetriol with 19 % overall yield (Scheme later found that a 8:2 mixture of the isomers (4R,8R)- and 29). Z-selective Wittig reaction allowed the preparation of 316 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.

1) Me(CH ) MgBr, Li CuCl , THF 1) LiAlH4, Et2O, 96% 2 11 2 4 OHC TsO 2) TsCl, Py 2) OsO4, NMO, tert-BuOH, Me2CO, H2O, 3 d., rt. then Na2SO4, 94% (3 Steps) 1) HIO H O, THF, (quant.) OH 4.2 2 5 1) MsCl, CH Cl , Py ( ) ( ) 2 2 13 ( )13 OTHP 2) THPO(CH ) MgBr, THF, 64% OH 2 5 OH 2) LiAlH4, THF 1) PTSA, THF, EtOH, 39 % (3 Steps) O LiC CTMS, THF, 86% OTHP ( )13 ( )8 ( )13 ( )7 H 2) PCC, NaOAc, MS 4Å, OH CH2Cl2, 72% OAc K CO , MeOH 2 3 ( )13 ( )7 OH ( ) ( ) Lipase PS-D, 13 7 99.5% e.e. 92.5% e.e. TMS ( )13 ( )7 CH2=CHOAc, (3R,11R) (3R,11R)-D TMS OH OH (i-Pr) O, 14 d., rt. (3RS,11R)-C 2 K CO , MeOH ( )13 ( )7 2 3 ( )13 ( )7

(3S,11R) TMS 98% e.e. 98.5% e.e. (3S,11R)-D OH

OH ( ) ( ) 13 7 Similarly Similarly ( )13 ( )7 OHC 97.5% e.e. 79% e.e. TMS (3R,11S)-D (3RS,11S)-C OH

( )13 ( )7 98% e.e. 94% e.e. (3S,11S)-D 1) TBSCl, imidazole, DMF, 76% OH 1) H2, PtO2, EtOAc, 15 min, rt. (3R,11R)-D ( )13 ( )7 2) n-BuLi, n-BuI, THF, HMPA, 75% 2) TBAF, THF, 92% (2 steps) ( )3 Ac2O, DMAP, OH OAc CH2Cl2, Py, 83% ( ) ( ) ( ) ( )13 ( )7 ( )5 13 7 5 98.5% e.e. 91% e.e. (7S,15R)-30 OAc Similarly ( )13 ( )7 ( )5 (3S,11R)-D 98% e.e. 97% e.e. (7R,15R)-30

OAc Similarly ( ) ( ) ( ) (3R,11S)-D 13 7 5 98% e.e. 83% e.e. (7S,15S)-30 OAc Similarly ( ) ( ) ( ) (3S,11S)-D 13 7 5 98% e.e. 96% e.e. (7R,15S)-30 Scheme 24. Synthesis of Pheromones Current Organic Chemistry, 2009, Vol. 13, No. 4 317

1.0% equiv. (S,S)-Z 1) Allyl MgBr, THF OO Br 6 0.6 equiv. H2O Br ( )

2) m-CPBA, CH Cl 2 2 OH OH OH OOO ( )6 ( )6 OH 6 + + HO ( ) OH A (2R,11S)-B

1) 2,2-DMP, H+ OR O 1) MeOH, H+ 6 O (2R,11S)-B ( ) o 2) MeMgBr, CuI, Et2O, 0 C 2) MsCl, Et3N 3) Ph3P, p-chlorobenzoic (R = p-ClPhCO) 3) K2CO3, MeOH acid, DEAD, THF OAc OAc OR 1) LiAlH4, Et2O O ( )6 ( )6

2) Ac O, Py 2 (2S,11S)-31 Scheme 25.

1.0% equiv. (R,R)-Z OO OH OH OH 7 0.6 equiv. H2O O ( ) 7 7 + ( ) OH HO ( ) OH C OO + 7 ( ) (2R,12R)-C 1) NaBH4, EtOH OAc OAc (2R,12R)-C ( )7 2) Ac2O, Py (2S,12S)-32 Scheme 26.

1.0% equiv.

3 m-CPBA, CH2Cl2 OO(R,R)-Z, 0.8 equiv. H2O ( ) 3 ( ) OH OH OH OOO 3 3 ( ) ( ) OH + HO ( )3 OH + B

o 2,2-DMP, H+ O 1) Me2CuLi, Et2O, 0 C O O B ( )3 O ( )3 O

2) MsCl, Et N 3 3) Me CuLi, Et O, 0oC 2 2 1) MeOH, H+ OCOEt O 1) NaBH4, EtOH ( )3 ( )3

2) MsCl, Et3N 2) (EtCO)2O, Py 33 3) K2CO3, MeOH

Scheme 27. the geometric isomer, (Z)-36 (-(Z)-acaridial), which was 6.3. (R)-10-Methyl-2-tridecanone (37) detected as a trace component in the secretion of C. poly- 10-Methyl-2-tridecanone (37) is the sex pheromone of phyllae, together with the (E)-configured hydroxy aldehyde the southern corn rootworm (Diabrotica undecimpunctata B. howardi), and biological evaluation of the enantiomers indi- 318 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.

O AcCH2CO2Et LiI Ref. [77] Br NaH DMF

CO2Et O N H , H O 1) O O 2 4 2 3 KOH OH OH 34 A 2) NaBH(OAc)3 B

MeCH=PPh3 H , Pd/C B 2 OH OH

O PCC

H 35 Scheme 28.

OH TBSCl, DMAP, OH O PDC, CH2Cl2 OH Et3N, CH2Cl2 OTBS OTBS HO TBSO TBSO A + - P Ph3Br OH H O OTBS Dess-Martin periodinane, O

CH2Cl2 TBAF, THF H

OTBS OH n-BuLi, Et2O H O

(E)-36

PDC, CH2Cl2 OH

P+Ph Br- 3 H B OTBS O 1) TBAF, THF H A OTBS 2) Dess-Martin periodinane, O NaHMDS, THF CH Cl 2 2 (Z)-36 Scheme 29.

o O O 1) EtMgBr, CuI 1) n-BuLi, THF, -78 C 7 ( )7 OBn 7 ( ) OBn ( )

2) MsCl, Et3N 2) PdCl , CuCl, DMF/H O, O 2 2 2 (R)-37 B o 3) Me2CuLi, Et2O, 0 C

Scheme 30. cated that the (R) enantiomer was preferred by males [82]. 6.4. (6R,12R)-6,12-Dimethylpentadecan-2-one (38) The epoxide (R)-B from scheme 22 was converted to (R)-37 (6R,12R)-6,12-Dimethylpentadecan-2-one (38) is the fe- in five steps (Scheme 30). male produced sex pheromone of the banded cucumber bee- Another synthesis took a similar approach as shown in tle (Diabrotica balteata), the larvae of which are serious scheme 3, starting from (+)-aromadendrene [16] (Scheme pests of crops such as cucurbits and sweet potatoes [83]. 31). Synthesis of Pheromones Current Organic Chemistry, 2009, Vol. 13, No. 4 319

O H H O H Ref. 16 CBr , PPh , CH Cl , 78% 4 3 2 2

H H H H H OH Br O OH 1) m-CPBA, MgSO4, CH2Cl2 1) NaOEt, NaBH , EtOH, 77% OEt 4

2) PTSA, EtOH, 59% overall H 2) H2, Pd/C, EtOAc, 83% Br

1) TsCl, Py, 79% OEt HO I O 2) LiAlH4, THF, 95%

A 3) I2, PPh3, imidazole, CH2Cl2, 91%

1) allylMgCl, THF, 83%

2) PdCl2, CuCl, O2, DMF O (wet) (100%). 37

Scheme 31.

1.0% equiv. 3 OO(R,R)-Z, 0.8 equiv. ( ) m-CPBA, CH2Cl2 3 ( ) H2O

OH OH OH OOO 3 ( ) ( )3 OH HO ( )3 OH + + B

o O 1) EtMgBr, CuI, Et2O, 0 C O DMP, H+ O 3 O B ( )3 O ( ) ( )2 2) MsCl, Et3N C o 3) Me2CuLi, Et2O, 0 C

1) MeOH, H+ O 1) H C=CH(CH ) MgBr, CuI, Et O, 0oC ( )3 2 2 2 2 ( ) 2 2) MsCl, Et3N 2) MsCl, Et3N 3) K CO , MeOH 2 3 o 3) Me2CuLi, Et2O, 0 C

1) PdCl , CuCl, O ( )3 2 3 ( )2 ( ) ( )2 DMF/H2O, O2 38 Scheme 32.

Chow and Kitching [59] described the synthesis of (6R,12R)- [84]. Addionally, 39 has been identified as a major sex 38 from epoxy-acetonide C (Scheme 32). pheromone component of O. vetusta [85] and was also found in the painted apple moth (Teia anartoides) [86]. 6.5. (6Z,8E)-Heneicosa-6,8-dien-11-one (39) and (Z)-6- Jury et al. [87] reported the synthesis of 39 in seven steps heneicosen-11-one (40) from 1,2-epoxydodecane in an overall yield of 25% (Scheme (6Z,8E)-Heneicosa-6,8-dien-11-one (39) and (6Z)- 33). (E)-Vinyl iodide B was obtained as a single stereoiso- heneicos-6-en-11-one (40) are sex pheromone components mer in good yield by the hydrozirconation–iodination of of the Douglas-fir tussock moth (Orgyia pseudotsugata) acetylene A with Schwartz’s reagent and freshly sublimed 320 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.

1) LiC CH:H NCH CH NH 2 2 2 2 OTBS 1) Cp2ZrHCl, benzene, rt., OTBS O DMSO, rt., 86% dark, 48 h ( ) ( )9 I 9 ( )9 2) TBDMSCl, imidazole, A 2) I2, 65% B DMF, 0oC, 97%

4 OTBS ( ) o 1-heptyne, PdCl2(CH3CN)2, 1) Ni(OA )2 .4H2O, NaBH4, EtOH, 0 C

( )9 CuI, piperidine, rt., quant. C 2) H2NCH2CH2NH2, H2, rt., 69%

O OTBS 1) TBAF, CH2Cl2, rt., 78%

( )9 ( )4 ( )9 ( )4 2) PCC, K2CO3, rt., CH2Cl2, 87% 39

Scheme 33.

O 1) NaBH , THF, 74% 4 OTBDMS 1) DIBAL-H, to uene, 94% MeO2C ( )9 MeO2C 2) TBDMSC , imidazo e, ( )9 2) PPh3 = CHCO2Me, DMF, 98% to uene, 96%

OTBDMS 1) DIBAL-H, to uene, 94% OTBDMS 1) CBr4, Ph3P, CH2C 2, 88% MeO C 2 OHC ( )9 ( )9 2) MnO2, CH2C 2, 96% 2) Pd(PPh3)3, (n-Bu)2SnH, benzene, quant.

1) n-C5H11MgBr, OTBDMS OH NiC 2, Et2O, 86% ( ) 9 ( )9 Br 2) TBAF, THF, quant.

Dess-Martin periodinane, O

CH2C 2, 79% ( )9

Scheme 34. iodine. The (E,Z)-diene system was obtained in good yield 6.6. (4S,6S,7S)-7-Hydroxy-4,6-dimethyl-3-nonanone (41) by the partial reduction of C in the presence of catalytic P2- (Serricornin) Ni under a hydrogen atmosphere. Serricornin [(4S,6S,7S)-7-hydroxy-4,6-dimethyl-3- Muto and Mori [31] described the synthesis of 39, em- nonanone), (4S,6S,7S)-41] is the sex pheromone produced by ploying a Wittig reaction for the formation of the (8E) dou- female cigarette beetle, Lasioderma serricorne.[90-95]. Zlo- ble bond, while the conjugated (6Z) double bond was estab- kazov and Veselovsky [96] developed a synthesis of 41 start- lished by Uenishi’s procedure (CBr4, PPh3) [88] (Scheme ing from (4S,5E)-4-methylhept-5-enenitrile [97] (Scheme 34). 37). Comeskey et al. [89] described the stereospecific synthesis of all four isomers of 39, using the Suzuki coupling of 6.7. (4R,6S,7R)-7-Hydroxy-4,6-dimethyl-3-nonanone (41) vinylic boronic acids A and C and vinylic iodide intermedi- and (3R,5S,6R)-6-hydroxy-3,5-dimethyl-2-octanone (42) ates B and D (Scheme 35). In 1999, Francke et al. found a stereoisomer of serri- Muto and Mori [31] described the synthesis of (Z)-6- cornin as a pheromone component of the beetle Dinoderus heneicosen-11-one (40), starting from 2-dodecanone in three bifoveolatus [98]. The synthesis of (4R,6S,7R)-41 and steps and 65% overall yield (Scheme 36). (3R,5S,6R)-6-hydroxy-3,5-dimethyl-2-nonanone (42) and Synthesis of Pheromones Current Organic Chemistry, 2009, Vol. 13, No. 4 321

I ( ) t2O, NaOH, I2, 53% 4 catecholborane 70oC, 55% (E)-B B(OH)2 ( )4 ( )4

(E)-A I t2O, THF, I2, 37% ( )4 (Z)-B

Br B(OH)2 AgNO , acetone, NBS, 46% HBBr2 then KIPBH, 78% 3 ( )4 ( ) ( )4 4 (Z)-A OH O lithium acetylide/ DA OH complex, DMSO, 82% catecholborane 70oC, 29% ( ) ( )9 9 B(OH)2 ( )9 OH t2O, THF, I2, 46% (E)-C

( )9 I (Z)-D

O 1) Pd(PPh3)4, NaO t, 36% (E)-C (E)-B ( )4 + ( ) 2) Dess - Martin periodinane, 72% 9 (E,E)-39 O 1) Pd(PPh3)4, NaO t, 66% (E)-C + (Z)-B ( )9 ( )4 2) Dess - Martin periodinane, 66% (E,Z)-39

O 1) Pd(PPh3)4, NaO t, 40% ( ) ( ) (Z)-D + (E)-A 9 4 2) Dess - Martin periodinane, 64% (Z,E)-39

O 1) Pd(PPh3)4, NaO t, 8% 4 ( ) (Z)-A ( )9 (Z)-D + 2) Dess - Martin periodinane, 78% (Z,Z)-39

Scheme 35.

O O NaH, CO(OMe) , (Z)-3-nonenyl iodide 2 ( )9 MeO2C ( )9 toluene, heat, 93% K2CO3, MeCOEt, 83%

O O

KOH, MeOH/H2O, 84% ( )9 ( )9 CO2Me 40 Scheme 36. their stereoisomers was performed by Masuda et al. [99]. 6.8. (E)-2,4-Dimethyl-2-hexenoic acid (43) The starting chiral building block A was obtained by lipase (E)-2,4-Dimethyl-2-hexenoic acid (43) is a caste-specific AK-catalyzed asymmetric acetylation of meso-2,4-dimethyl- substance present in the mandibular glands of male ants in 1,5-pentanediol. Asymmetric acetylation with vinyl acetate the genus Camponotus [100]. Fernandes et al. [101] de- and lipase PS-D (Amano) furnished the acetate (2R,4S,5R)-B scribed a synthesis of 43 with high stereoselectivity and 39% and the alcohol (2R,4S,5S)-C, which were further trans- overall yield, by zinc-promoted reduction of the 2-(bromo- formed to the target compounds (Scheme 38). 322 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.

I I + NaOH E,OH, 1) NIS, DMF, 20 C + HO O O CN sealed ,ube, 200+C 2) )hr+ma,+graphy O O O A 4 3:2

+ 1) n-Bu3SnH AIBN, benzene, 80 C + 4 E,MgBr, THF, - 40 C O 2) (TMS) NLi, THF HMPA, 2 OH O + + + -78 C ,+ 10 C, ,hen MeI, -78 C O (4S,6S,7S)-41 Scheme 37.

CH2 =CHOAc, lipase AK, 86% HO OH OOO

1)TB MSCl, imidazole, MF, 95% HO OAc

A 2) K2CO3, MeOH, 96%

3) TPAP, NMO, CH2Cl2

4) EtMgBr, THF, (2 steps, 73%) TB MSO

OAc CH2 =CHOAc, TB MSO lipase PS- (2R,4S,5R)-B, 27%

TB MSO

OH (2R,4S,5S)-C, 64%

EtMgBr, THF

OOH

1) TBAF, THF, %uant. (4R,6S,7R)-41

(2R,4S,5R)-B OO 2) KOH, MeOH, 87% MeMgBr, THF 3) TPAP, NMO, CH2Cl2, 79% OOH (3R,5S,6R)-42

EtMgBr, THF

OOH 1) TBAF, THF, 92% (2R,4S,5S)-C (4R,6S,7S)-41 OO 2) TPAP, NMO, CH2Cl2, 78% MeMgBr, THF

O OH (3R,5S,6S)-42 Scheme 38. Synthesis of Pheromones Current Organic Chemistry, 2009, Vol. 13, No. 4 323

O O OH O HBr, H SO , 75% DABCO, 72% 2 4 + OCH H 3 OCH3 A O O

OCH 1) Zn/A%OH, 88% 3 OH

Br 2) N OH, MeOH/H2O, 83% B 43 39% ) / er ll yield Scheme 39.

1) (CH3)2CH2I, O O o O 1) AD-mix- , H2O/t-BuOH, 0 C O t-BuOK, DMSO P O O O 2) KOH, H2O/ tOH 2) LiHMDS, CH3CHO, THF, -78 oC

O O OH O MsCl, Py, 0 oC HO OH OH (S,S)-44

O AD-mix- , H O/t-BuOH, 0 oC O 2 O Similarly O OH

(R,R)-44

1) (CH3)2CH2I, O O t-BuOK, DMSO O O CF3 NaHMDS, 18-crown-6, O O P P CF3 CH CHO, THF, -78 oC O O 3 o O O 2) PCl5, 75 C

3) CF3CH2OH,

toluene, t N 3 O O O OH O O 1) AD-mix- , H O/t-BuOH, 0 oC 2 HO MsCl, Py, 0 oC

2) LiOH, H O/i-PrOH OH 2 OH

O (S,S)-45 O o O AD-mix- , H2O/t-BuOH, 0 C Similarly O OH

(R,R)-45 Scheme 40. methyl) alkenoate B derived from the corresponding Baylis– ture of compounds containing alkaloids, aromatics, terpe- Hillman adduct A (Scheme 39). noids, hydrocarbons, and lactones, during courtship. 7. SYNTHESIS OF LACTONES AS PHEROMONES The pure (S,S) and (R,R) enantiomers of the -lactones 2- hydroxy-2-(1-methylethyl)-3-butanolide (44) and 2-ethyl-2- 7.1. 2-Hydroxy-2-(1-methylethyl)-3-butanolide (44), 2- hydroxy-3-butanolide (45) were synthesized based on a con- ethyl-2-hydroxy-3-butanolide (45), 7-hydroxy-5- trolled C-C coupling by a Horner-Wadsworth-Emmons ap- dodecanolide (46) proach, followed by asymmetric dihydroxylation (Scheme 40). The absolute configuration of the natural lactones was Schulz and Nishida [102, 103] reported that males of the determined to be (S,S) by enantioselective gas chromatogra- giant white butterfly Idea leuconoe release a complex mix- phy [104]. 324 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.

OO O O 1) SnC 2, N2CH2COOEt, CH2C 2

O H 2) Mg(OEt)2, C CO(CH2)3COOMe, Et2O

3) NaC , D, DMSO/H2O

OH OH O 1) H , (R)-Ru-BINAP, MeOH OH OH O 2 o( o( NaBH4, MeOH, O O

O O

O OH O OH PTSA, CHC 3 o( O

(R,R) - 46 rac - 46

1) PPh3, DEAD, O benzoic acid, CH2C 2 O OH 2) NaOMe, MeOH

(R,S) - 46 Scheme 41.

SiMe O HO 3 1% HF aq., rt., 1.5 h, 96% LDA, -78 oC, then SiMe3O O O 2% TBDPSCl, imidazole, O CH3CH2CHO, 3 h, 93% OH DMF, rt., 12 h, 94% OTBDPS

1% CAN, acetonitrile, o OTBDPS OTBDPS 1% MsCl, Et3N, 0 C, 3h 0oC, 20 min, 92% NC HO o 2% NaI, acetone, reflux. 12 h 2% BH3 THF, 0. C, 3% NaCN, DMSO, rt., then rt., 4 h, 95% 12 h, 80% overall

1% NaOH, 2-methoxyethanol, reflux, 21 h, then HCl, 90% O O

2% TBAF, THF, rt., 4 h, 86% R%-47 Scheme 42.

The -lactone 7-hydroxy-5-dodecanolide (46) was syn- Arceo et al. [107] described the synthesis of 47 with 45% thesized as a mixture of stereoisomers and as the pure (R,R) overall yield in high enantiomeric purity using a chiral auxil- isomer, the latter by enantioselective reduction of the methyl iary derived from (S)-camphor (Scheme 42). dioxoalkanoate precursor employing Ru-BINAP catalyst. The (R,S) isomer was obtained by Mitsunobu inversion of 7.3. (4R,9Z)-Octadec-9-en-4-olide (48) the (R,R) isomer (Scheme 41). The natural product was Cossé et al. [108] reported the occurrence of a female- shown to be a mixture of all stereoisomers [104]. specific compound from the currant stem girdler (Janus inte- ger), which they identified as the chiral lactone (Z)-octadec- 7.2. (R)-4-Hexanolide (47) 9-en-4-olide (48). The structure was proven by synthesis of (R)-4-Hexanolide (47) was identified as a component of the racemic compound. Upon chiral GC analysis, only one the sex pheromone of females of the dermestid beetle Tro- enantiomer was detected to be produced by the insects, but goderma glabrum [105, 106]. the absolute configuration was not determined. Synthesis of Pheromones Current Organic Chemistry, 2009, Vol. 13, No. 4 325

DHP, CH C PDC, CH2C 2 OH 2 2 H OH THPO HO THPO O 0,1N HC , rt. MgSO4, rt. B A, THF, 0 oC, then TPAP, NMO ( )7 HO ( )7 O O OH CH2C 2, rt. NH4C , MeOH, ref ux (±)-48 NH2 HONO 1) BH3.Me2S HOOC COOH O O COOH OTs O O 2) TsC , TMPDA, 0 - 5 oC O NaOMe, C, THF, 0oC 7 O ( ) O O O anhydrous MeOH, rt. D (R)-48

A BrMg ( )7

C BrMg ( )7 Scheme 43.

O CH CLi .H N(CH ) NH , Ref. 111 2 2 2 2 HO OH TBDPSO THF, 62% ( )6 ( ) H 5 OH OAc OH Lipase AH-S (Amano), TBDPSO TBDPSO ( ) + TBDPSO CH2 CHOAc, 5 ( )5 ( )5 B (+)-A 29% yield, 96% e.e. rac. - A SiO2 chromatography OH TBDPSO K2CO3, MeOH ( )5 (-)-A 24% yield (2 steps), 93% e.e.

OTBS OH 1) TBSCl, imidazole, DMF, 94% 1) H , PtO , hexane, 89% TBDPSO 2 2 (+)-A HO ( )5 ( )5 CO2Me 2) n-BuLi, ClCO Me, THF, 94% 2 CO2Me 2) TBAF, THF 1) PCC, MS 4Å

1) KOH, MeOH, H2O sieves, CH2Cl2, 68% HO O ( )5 O O ( )7 ( )4 O + - 2) dil. HCl (79%; 3 steps) 2) [Me(CH2)8PPh3 ]Br , NaHMDS, (R)-48 hexane, THF, -100 oC, 68% Similarly (95.9% e.e., E/Z 1.6:98.4)

(-)-A ( ) O ( )7 4 O (S)-48 (94.9% e.e., E/Z 1.6:98.4)

Scheme 44.

James et al. [109] described the synthesis of racemic and Shibata and Mori [110] synthesized both enantiomers of the pure enantiomers of 48 and determined the absolute con- 48. The key step was the lipase-catalyzed asymmetric acety- figuration of the natural compound to be (R). In the racemic lation of a racemic mixture of the acetylenic alcohol A with route, Grignard reagent A was added to aldehyde B, fol- vinyl acetate and lipase AH-S, which furnished (+)-A (96% lowed by deprotection and selective oxidation of the primary e.e.) and the acetylated product B, which was hydrolyzed to hydroxyl group with tetrapropylammonium perruthenate (TPAP). (R)-48 was synthesized by addition of Grignard give (-)-A (93% e.e.). (+)-A and (-)-A were transformed to reagent C to the chiral epoxide D prepared from (S)-(+)- (R)-48 and (S)-48, respectively (Scheme 44). glutamic acid (Scheme 43). 326 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.

O O N 1) n-BuLi, THF, -78oC N OH + H3O O O O H H 2) + HO H 92% O 85%

I cis - (2R,5S)-49 trans - (2S,5S)-49 (S)-A (from ref. 115) (cis/trans = 7:3) 78% overall from iodide (S)-A

HO H O O I (R)-A (from ref. 115) O O H + H similarly

cis - (2S,5R)-49 trans -(2R,5R)-49 (cis/trans = 7:3) 80% overall from iodide (R)-A

o n-BuLi, THF, -78 C + H N O H , MeOH O HO O O O O 85% 60% O N 51% overall yield from iodide B O I

B (from ref. [116])

Ref. [117] O O 50 Scheme 45. OH O OH O O O L-proline (20 mol%), CHCl , 24 h, 80% 3 ( )9 ( )9 H + +

A 85 : 15

96% e.e. OAc O m-CPBA, CH2Cl2,

NaHCO3, rt., 82 - 85% Ac2O, Py, DMAP, rt., 100% A ( )9

m-CPBA, CH2Cl2, OH

NaHCO3, r.t., 82 - 85% A O O Ac2O, Py, DMAP, rt., 100% ( )9 OAc

O O

51 Scheme 46. 7.4. cis- and trans-2-Methyl-5-hexanolide (49) and (4R, starting materials derived from 2-oxazolines. To show the 5Z)-tetradec-5-en-4-olide (50) usefulness of this approach, the diastereoselective synthesis of cis- and trans-49 and a formal synthesis of (4R,5Z)-50 cis-2-Methyl-5-hexanolide (49) is a component of the were performed (Scheme 45). pheromone blend of the carpenter bee Xylocopa hirutissima [112], while (4R,5Z)-tetradec-5-en-4-olide (50) is the sex 7.5. (5R,6S)-6-Acetoxyhexadecane-5-olide (51) pheromone of the Japanese beetle, Popillia japonica [113]. Laurence and Pickett described for the first time a natural Zarbin et al. [114] proposed a general approach to the syn- mosquito oviposition attractant pheromone in 1982 [118]. A thesis of chiral pheromone lactones using readily available synthesis of the compound, (5R,6S)-6-acetoxyhexadecane-5- Synthesis of Pheromones Current Organic Chemistry, 2009, Vol. 13, No. 4 327

1) CrCO , DMF/MeOH, O 3 pH 7.0, BnBr, rt., 17 h, 84% O OBn OH OH O O OO 2) NaBH4, Et2O/MeOH, (S)-A; 92% e.e. -20oC, 2h, 95% 3) PPL, Et O, 30oC, 24 h, 74% 2 1) Pd/C 10%, H , 1 atm, 3 h, 95% 2 O H O

2) BH3.DMS, THF, rt., 2 h, 90% O (S)- B 3) PCC, CH Cl , rt., 2 h 90% 2 2

DIBAL-H, THF, HO OBn (S)-A O -78oC, 2h, 71% O (R)- C

o (S)-B, THF, -100 C, 1.5 h, 60% O O (S) - 52 Z/E = 96:4; 27% overall yield; 92% e.e. ( )6 PPh3 (R)-C, THF, -100oC, 1.5 h, 55%

O O (R) - 52 Scheme 47. Z/E = 96:4; 18% overall yield; 92% e.e.

Br2 Br DMPU Br Br + vinylic isomers isoprene 1) In, NaI, DMF, 3-methylbutanal, 91% OH

2) NH4Cl/H2O 53 Scheme 48. olide (51) was carried out by Sun et al. [119], employing a scribed a short synthesis of racemic 53 employing a selective L-proline-catalyzed asymmetric aldol condensation between indium insertion on a mixture of 2-bromomethylbuta-1,3- cyclopentanone and undecanal, followed by oxidation and diene and its vinylic isomers, in good yields (Scheme 48). acetylation (Scheme 46). 8.1.2. (1R,3R)-(3-Isopropenyl-2,2-dimethylcyclobutyl) 7.6. (Z)-Hexadeca-7,15-dien-4-olide (52) methyl 3-methyl-3-butenoate (54) (Z)-Hexadeca-7,15-dien-4-olide (52) was described by (1R,3R)-(3-Isopropenyl-2,2-dimethylcyclobutyl)methyl Leal et al. [120] as the female sex pheromone of the yel- 3-methyl-3-butenoate (54) has been identified as the sex lowish elongate chafer (Heptophylla picea). Clososki et al. pheromone produced by virgin females of the mealybug [121] described an enzymatic synthesis of (R)- and (S)-52. A Pseudococcus cryptus [124]. known lipase-catalysed enantiolactonization in the key step Nakahata et al. [125] acetylated (+)--pinene with lead afforded the common precursor (S)-A for both enantiomers acetate and cleaved the resulting acetate by ozonolysis. The of the pheromone, in 92% e.e. (overall yield: 27% for (S) and triol obtained by reductive workup was reacted with 18% for (R)-isomer) (Scheme 47). trimethyl orthoformate, and subsequent treatment with acetic acid yielded the alcohol A, which was esterified to give 54 in 8. SYNTHESIS OF ISOPRENOIDS AS PHEROMONES 43% overall yield (Scheme 49). 8.1. Synthesis of Isoprenoidal Alcohols As Pheromones 8.1.3. (1R,3R)-(3-Isopropenyl-2,2-dimethylcyclobutyl) 8.1.1. 2-Methyl-6-methyleneoct-7-en-4-ol (53) (ipsenol) methyl acetate (55) Ipsenol (2-methyl-6-methyleneoct-7-en-4-ol, 53) was (1R,3R)-(3-Isopropenyl-2,2-dimethylcyclobutyl)methyl identified as the aggregation pheromone of the California acetate (55) has been identified as the female-produced sex bark beetle (Ips paraconfusus) [122]. Ceschi et al. [123] de- pheromone of the citrus mealybug (Planococcus citri) which 328 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.

OH O , MeOH, then Pd(OAc) , 3 4 OAc + OH HO NaBH4, K2CO3, 72% benzene, 75% OAc (95:5)

DCC, DMAP,

1) HC(OMe)3, PPTS, THF CH2Cl2, 91% O

HO OH 2) Ac2O, then NaOH (88% overall) O

A O 54

Scheme 49.

RuCl3 - NaIO4, COOH 1) Pb(OAc)4, benzene CH3CN/CCl4/H2O

2) MeOH, KOH, 55% (2 steps) O (+)--pinene OH (+)-trans-verbenol - A COOH OAc 1) (CH3)3SiCH2MgCl 1) LiAlH , Et O 4 2

2) Ac2O 2) Ac2O, Py 55

RuCl3 - NaIO4, COOH acetone, N-hydroxyphthalimide, t-BuOH/H2O

O CrO , 36% (+)--pinene 3 O (+)-R-verbenone - B

COOH OAc Zn, CH2Br2, TiCl4 1) LiAlH4, Et2O

2) Ac2O, Py 55

Scheme 50. is a major pest of coffee, citrus, and cocoa in both the south- The synthesis of a mixture of grandisol and its di- ern U. S. and the Mediterranean [126]. astereomer fragranol was described by Bernard et al. [132] Pássaro and Webster described two alternative syntheses and is shown in Scheme 51. Key step is the palladium(0)- of 55 [127]. Compound 55 was synthesized starting from catalysed reduction of the 2-cyclobutylidenepropyl sulfonic (+)-trans-verbenol A or (+)-(R)-verbenone B, obtained from ester A (E:Z 30:70) by ammonium formate to furnish (±)-56 -pinene. The key step for both syntheses is the oxidative and (±)-fragranol in 70:30 ratio. decarboxylation using RuCl3-NaIO4 (Scheme 50). 8.2. Synthesis of Isoprenoidal Aldehydes and Ketones as 8.1.4. cis-2-(2-Isopropenyl-1-methylcyclobutyl)ethanol (56) Pheromones (grandisol) 8.2.1. (Z)-exo--Bergamotenal (57) Grandisol [cis-2-(2-isopropenyl-1-methylcyclobutyl) ethanol, 56] is the major component of the male-produced Alizadeh et al. [133] described the synthesis of a racemic pheromone of the cotton boll weevil (Anthonomus grandis) mixture of (Z)-exo--bergamotenal (57), a sex pheromone [128] and was also identified from other pests, like bark component of the white-spotted spined bug Eysarcoris par- weevils [129, 130] and bark beetles [131]. vus, from racemic exo--bergamotene by a five-step se- Synthesis of Pheromones Current Organic Chemistry, 2009, Vol. 13, No. 4 329

O SPh O SPh n-BuLi PTSA

+ OBn H OBn THF, 0oC OH benzene, , 98% OBn

COOEt P(O)OEt2 CH OTs Pd(dba)2, PPh3, 2 CH3CN, HCOONH4 + 1) NaH, TDA-1, THF, OBn OBn OBn 2) LiAlH 4 (70:30) A 3) TsCl, DMAP, NEt3

Li/NH3 +

OH OH 56 (70:30) Scheme 51.

O COCl Ref. 134 1) N2H4, AcOH, EtOH

2) t-BuOK, DMSO

m-CPBA, aq. O H IO , H O/THF 5 6 2 OHC

NaHCO3, CH2Cl2

1) NaH, (o-Tolyl-O)2P(O)CH(CH3)CO2Et, THF

2) DIBAL - H, THF CHO 3) MnO2, hexane 57 Scheme 52. quence involving regioselective epoxidation and (Z)- mone from the Colorado potato beetle (Leptinotarsa decem- selective Wittig olefination reactions (Scheme 52). lineata). The absolute configuration of natural 59 was de- 8.2.2. Iridodial (58) termined to be (S) by syntheses of the racemate and both enantiomers from geraniol and (R)- and (S)-linalool, respec- In 2004, Zhang et al. [135] identified iridodial [(1R,2S, tively, by Oliver et al. [139] (Scheme 54). 5R,8R)-(2-(1-formylethyl)-3-methylcyclopentanecarboxalde- hyde, 58] as a male-produced male-aggregation pheromone 9. SYNTHESIS OF ACETALS AS PHEROMONES of Chrysopa oculata, the first pheromone identified from lacewings. 9.1. 4-Hydroxy-1,7-dioxaspiro[5.5]undecane (60) Chauhan et al. [136] described the synthesis of (1R,2S,5R,8R)-58 and of the diastereomers (1R,2S,5R,8S)- Baker and co-workers described the isolation and identi- 58, (1S,2S,5R,8R)-58, and (1S,2S,5R,8S)-58 in five steps fication of 4-hydroxy-1,7-dioxaspiro[5.5]undecane (60), a from (4aS,7S,7aR) and (4aS,7S,7aS)-nepetalactones, which minor component of the female-produced sex pheromone of have been isolated by chemical separation from catnip (Ne- the olive fruit fly, Bactrocera oleae, establishing the most peta cataria) oil [137] (Scheme 53). favorable configuration as (4S,6S) [140, 141]. Hao and For- 8.2.3. 3,7-Dimethyl-2-oxooct-6-ene-1,3-diol (59) syth [142] described a short total synthesis of 60 employing a double intramolecular hetero-Michael addition strategy, Dickens et al. [138] identified 3,7-dimethyl-2-oxooct-6- applicable to spiroketal synthesis (Scheme 55). ene-1,3-diol (59) as the male-produced aggregation phero- 330 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.

NaHCO3 (5%), COOCH3 1) HOCH CH OH, toluene, cat. O 2 2 MeOH/H2O (95:5), rt. TsOH, azeotropic dehydration CHO 2) flash chromatography

COOCH3 COOCH3 O O

+ O O

A B

CHO 1) DIBAL - H, toluene, -78 to 0 oC CHO O THF, 2N HCl, rt. A CHO 2) PDC, dry CH2Cl2, rt. O

(1R,2S,5R,8R)-58 Similarly CHO

B CHO

(1R,2S,5R,8S)-58

O CHO CHO

Similarly O CHO CHO

(1S,2S,5R,8R)-58 (1S,2S,5R,8S)-58 Scheme 53.

O OH 1) t-BuOOH, VO(acac)2 OAc

OH 2) Ac2O, Py

geraniol 1) HClO4, DMF * OH

OH OH OH 2) K2CO3, MeOH * t-BuOOH, VO(acac)2 * O A: racemic B: 3-(S) C: 3-(R) (R)- and (S)-linalool OH OH

* OTBDPS * OH 1)TBDPSCl, imidazole A: racemic O TBAF O B: 3-(S) C: 3-(R) 2) Swern oxidation racemic 59 (S)-59 (R)-59 Scheme 54. Synthesis of Pheromones Current Organic Chemistry, 2009, Vol. 13, No. 4 331

1) n-BuLi, TBSOCH2CH2CHO OTBS TBSO 2) MnO2, 75% (2 steps) OTBS

O CSA, MeOH O 1) NaBH4, MeOH

then benzene, 70% 2) PTSA, MeOH O O 82% (2 steps) HO O 60 Scheme 55.

1) MsCl, Py 1) Mg, Et2O OH Br Br (Z) or (E) 2) LiBr, Acetone 2) (Z) or (E)

O O m-CPBA, CH2Cl2 or

rac-cis- A rac-trans- B

Mycobacterium

paraffinicum OH PdCl2, cat. CuCl2 NCIMB 10420 O MeO(CH2)2OMe rac-cis- A O

buffer pH 7.5, 83% OH

92% e.e. (+)-exo - 61 Mycobacterium paraffinicum OH NCIMB 10420 PdCl2, cat. CuCl2 rac-trans- B O MeO(CH2)2OMe buffer pH 7.5, 83% OH O

92% e.e. (-)-endo - 62 Scheme 56.

9.2. 7-Ethyl-5-methyl-6,8-dioxabicyclo[3.2.1]octane (61) 9.4. 1,5-Dimethyl-6,8-dioxabicyclo[3.2.1octane (64) (fron- [exo-(61) and endo-brevicomin (62)] talin) exo-Brevicomin (61) and endo-brevicomin (62) are typi- Frontalin (1,5-dimethyl-6,8-dioxabicyclo[3.2.1]octane, cal components of the aggregation pheromone system of 64) was first isolated by Kinzer [151], and is a component of several bark beetle species of the genera Dendroctonus and the aggregation pheromone of the southern pine beetle (Den- Dryocoetes [143-146]. Mayer et al. [147] synthesized droctonus frontalis), and of the western pine beetle, Den- (1R,5S,7R)-61 and (1S,5R,7R)-62, employing an enantiocon- droctonus brevicomis. By means of bioassays with pure syn- vergent biocatalytic hydrolysis of cis-configured 2,3- thetic enantiomers, Mori [145, 152] has shown that the abso- disubstituted oxiranes by bacterial epoxide hydrolases lute configuration of natural 64 is (1S,5R). Chênevert and (Scheme 56). Caron [153] described an enantioselective synthesis of 9.3. (1R,5S,7R)-exo-Brevicomin (61), (1R,1’R,5’R,7’R)- (1S,5R)-(–)-64 in 90% e.e. via enzymatic desymmetrization and (1S,1’R,5’R,7’R)-1-hydroxy-exo-brevicomin (63) of an achiral triol (Scheme 58). A synthesis of racemic 64 was performed by Yang [154] Francke et al. [148] have identified 1-hydroxy-exo- et al. Diene A was subjected to a double dihydroxylation brevicomin (63) from the pine beetle Dendroctonus pon- with catalytic osmium tetroxide and 4-methylmorpholine-N- derosae. Kumar and Rao [149] described a synthesis of oxide in MeCN–MeCOMe–H O (1:1:1), generating tetraol (1R,1’R,5’R,7’R)-63 and (1S,1’R,5’R,7’R)-63 and of 2 B. Subsequently, mono cleavage and acid-catalyzed in- (1R,5S,7R)-61, starting from -picoline ((Scheme 57) (Table tramolecular acetalation led to 64. Use of AD-mix- in the 1)). 332 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.

Ph3PCHCOCH3, CH2Cl2, 3 h

Na in liq. NH3.EtOH 4N HCl OO(overall yield for three steps 35%) N H N H A

OOAD-mix- , t-BuOH/H O, PTSA (cat.), 2 OOOH 1:1, 3 h, 0oC CH2Cl2, 54% (2 steps)

O O O Table 1

O O + O

O OH OH (1R,1'R,5'R,7'R)-63 (1S,1'R,5'R,7'R)-63

Ph PCHCOOEt, CH Cl 30 min 3 2 2 AD-mix- , t-BuOH/H O, OO 2 OOOH (overall yield for three steps 25%) 1:1, 3 h, 0oC

A OEt OEt OH PTSA (cat.), LiCl, NaBH4, O CH2Cl2, 54% (2 steps) O EtOH, THF, 77% Ref. 150 O O O OEt O

OH 61 O Scheme 57.

Table 1.

Solv.s and Temperature Yield (%) (1R,1’R,5’R,7’R)-(63) (1S,1’R,5’R,7’R)-(63)

o Li AlH4 THF, 0 C 86 32 68

o NaBH4 MeOH, 0 C 92 36 64

o Zn(BH4)2 THF, 0 C 84 25 75

K-Selectride Toluene, -78oC 79 22 78

DIBAL-H THF, 0oC 92 20 80 dihydroxylation step resulted in only poor enantioselectivity tion pheromone isolated from the frass of the female ambro- (16% e.e.) (Scheme 59). sia beetle Trypodendron lineatum, which is a deleterious pest to coniferous forests in Europe and North America [158]. 9.5. 1,3,8-Trimethyl-2,9-dioxabicyclo[3.3.1]non-7-ene (65) Alibés [159] et al. described a highly stereoselective In 2001, Nakashima [155] reported the identification of formal synthesis of (+)-lineatin in 14 steps and 14% overall yield from the homochiral furanone A (Scheme 61). Key 1,3,8-trimethyl-2,9-dioxabicyclo[3.3.1]non-7-ene (65) from steps of this synthetic approach feature the diastereoselective the hexane extract of the brush organ located at the hind legs construction of the cyclobutene derivative B by a photo- of male swift moths Endoclita excrescens. chemical cycloaddition, and a regiocontrolled oxymercura- The absolute configuration was determined by synthesis tion reaction to form the dihydroxy compound C. in a preliminary communication by Marukawa and Mori [156]. The same authors reported the synthesis of the 10. SYNTHESIS OF AN AMIDE AS PHEROMONE (1R,3S,5S)- and (1S,3R,5R)-isomers, starting from the pure enantiomers of ethyl 3-hydroxybutanoate [157] (Scheme 60). 10.1. (1’S,2R,2’S,3’R)-N-(1’-(Hydroxymethyl)-2’,3’-dihydroxytetradecyl)-2-hydroxy-21-methyldocosanamide (67) 9.6. (+)-Lineatin (66) Asai et al. [162] reported in 2000 the ceramide (1’S,2R, Lineatin [3,3,7-trimethyl-2,9-dioxatricyclo[3.3.1.04,7]no- 2’S,3’R)-N-(1’-(hydroxymethyl)-2’,3’-dihydroxytetradecyl)- nane, 66] is the most important constituent of the aggrega- 2-hydroxy-21-methyldocosanamide (67) to be the sex phero- Synthesis of Pheromones Current Organic Chemistry, 2009, Vol. 13, No. 4 333

O OH O O 1) THF -78oC O O MgBr + TBDPSO OTBDPS OH 2) TBAF, THF OH Pseudomonas sp. lipase, OH OH O O O O OAc + OAc vinyl acetate, benzene

(R)-A OH OAc O 1) TsCl, DMAP, Py, O LiEt BH, THF, 2) PTSA, CH2Cl2, H2O. 3 (R)-A OTs O O reflux 64 TsCl, Et3N, DMAP, CH2Cl2 PTSA,

OAc OH Et2O, H2O LiAlH , THF O O O 4 O O OH

Scheme 58. OsO4, NMO MeCN/acetone/H2O OH OH (1:1:1), 0°C, rt. OH OH

A O B HCl, H5IO6, H2O,

O Et O, , 64% 2 64 O

1) AD-mix-, t-BuOH, H O 2 (1:1), 0°C, rt. O

A 2) HCl, H IO , H O, 5 6 2 (-)-64 16% e.e. Et2O, , 55% Scheme 59.

OH O 1) TBDMSCl, imidazole, DMF, 91%

+ O O O 2) DIBAL-H, CH2Cl2, 88% OH OTBDMS OH OTBDMS 3) 2,3-dimethylfuran, t-BuLi, Et2O/HMPA A 35% B 27% 4) chromatography 48% HF aq., O O m-CPBA,CH2Cl2, 89% MeCN, 79% A H OTBDMS O

O O OH 1) NaBH4, CeCl3.7H2O, (n-Bu)3SnH, AIBN, OCS2Me MeOH, 94% toluene, 76% O O O O 2) n-BuLi, CS2, MeI, THF, 98% (1R,3S,5S) - 65

Similarly OH O O O O Scheme 60. (1S,3R,5R) - 65 334 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.

O O PivO 76% d.e.

O O (Z)-1,2-dichloroethylene, hn, O O H PivO PivO o Zn, EtOH (80%), CH3CN, -15 C, 89% B MW, 105oC anti H O O A PivO Cl Cl + H syn

O OH O OH O o O 1) Hg(OAc) , THF/H O, rt. 1) MeLi, THF, -78 C, 86% 2 2 1) NaH, BnBr, THF, rt., 79% B H H 2) PTSA, acetone, rt. 91% 2) NaBH4, NaOH, rt., 92% 2) TFA, MeOH/H O, rt., 94% OH 2 C

OH OH O HO 1) TsCl, DMAP (cat.), Py, reflux, 84% o ImCSO 1) Bu3SnH, AIBN, toluene, 100 C, 93% H H 2) TCDI, THF, 70oC, 90% 2) H , Pd/C, HOAc, rt. 98%. OBn OBn 2

O O O O 1) Dess-Martin periodinane, CH Cl , rt. 2 2 Ref. [160, 161] O H H H 2) RuCl3, NaIO4, CCl4,/H2O, rt. (81%, 2 steps) OH O >99.5% e.e. (+)-66 Scheme 61.

1) (CH3)2CH(CH2)2MgBr, 1) PTSA, EtOH, 97% Br Li2CuCl4, THF, 99% HO ( )11 THPO ( )19 HO2C ( )19 2) TsCl, Py, 89% 2) Jones' CrO3, acetone, 74%

3) THPO(CH2)6MgBr,

Li2CuCl4, THF, 79%

1) CH =CHOCOCH , TBDMSO 1) Br2, P, , 84% OH 2 3 Lipase PS, BHT, THF, 23% CO H ( ) CO H ( ) 2 18 2) NaOH, H2O, 90% 2 18 2) TBDMSCl, imidazole, DMF, 80% A

HC C(CH2)9CH3, OH Ref. [164,165] CHO n-BuLi, THF, 85% (S) - Serine O O NBoc NBoc ( )9

OTBDMS 1) Li, C2H5NH2 OTBDMS 1) TsCl, Py, 90%

( ) TBDMSO ( )9 TBDMSO 9 2) TBDMSOTf, 2,6-lutidine, 2) DMD, acetone, 68% NHTs NH2 CH2Cl2, 72% (2 steps) 3) DIBAL-H, toluene, 84%

Synthesis of Pheromones Current Organic Chemistry, 2009, Vol. 13, No. 4 335

Scheme 61 contd....

OTBDMS 1) Na, naphthalene, DME

TBDMSO ( )9

NH OTBDMS 2) TBSOTf, 2,6-lutidine, 2 CH2Cl2, 81% (2 steps) B OH

1) EDC, HOBt, CH2Cl2, 55% HO A + B OH OH 2) TBAF, THF, 71% HN

O 67 Scheme 62. mone of the female hair crab, Erimacrus isenbeckii. Masuda HONO = gaseous nitrous acid et al. [163] described a enantiodivergent synthesis, employ- KIPBH = potassium tri-isopropoxyborohy- ing 12-bromododecan-1-ol for the synthesis of the acid moi- dride ety A with a lipase-catalyzed resolution of hydroxy-acid in the key step, and (S)-serine for the construction of the amine LDA = lithium diisopropylamide moiety B, which were reacted to give the amide 67 (Scheme LiHMDS = lithium hexamethyldisilazide 62). m-CPBA = m-chloroperbenzoic acid ACKNOWLEDGEMENTS MeCBS = methyl oxazaborolidine MsCl = methanesulfonyl chloride (mesyl The Brazilian authors want to thank Capes, Fundação chloride) Araucária and CNPq for financial support. JB thanks the Dirección de Investigación of PUCV and Fondecyt for fi- NaHMDS = sodium hexamethyldisilazide nancial support. NIS = N-iodosuccinimide NMO = N-methylmorpholine-N-oxide ABBREVIATIONS PCC = pyridinium chlorochromate Ac = acetyl PDC = pyridinium dichromate AIBN = azobisisobutyronitrile PPh3 = triphenyl phosphine BnBr = benzyl bromide PPL = porcine pancreatic lipase CAN = ceric ammonium nitrate PPTS = pyridinium p-toluenesulfonate CSA = camphorsulfonic acid PTSA = p-toluenesulfonic acid DABCO = 1,4-diazabicyclo[2.2.2]octane Py = pyridine DEAD = diethyl azodicarboxylate SOCl = thionyl chloride DET = diethyl tartrate 2 TBAF = tetra-n-butylammonium fluoride DHP = 3,4-dihydro-2H-pyran TBDMSCl = tert-butyldimethylsilyl chloride (DHQ)2-PHAL = hydroquinine 1,4-phthalazinediyl diether TBDPSCl = tert-butyldiphenylchlorosilane DIBAL-H = diisobutylaluminium hydride TCDI = 1,1'-thiocarbonyldiimidazole DIPEA = ethyldiisopropylamine TDA-1 = tris-(3,6-dioxaheptyl)amine DMAP = 4-dimethylaminopyridine TFA = trifluoroacetic acid DME = dimethoxyethane THF = tetrahydrofurane 2,2-DMP = 2,2-dimethoxypropane THP = tetrahydropyranyl DMF = N,N-dimethylformamide TMEDA = tetramethylethylenediamine DMPU = 1,3-dimethyltetrahydropyrimidin- TMPDA = tetramethylpropylenediamine 2(1H)-one TMSCl = trimethylsilyl chloride DMSO = dimethylsulfoxide TMSOTf = trimethylsilyl trifluoromethanesul- HMPA = hexamethylphosphoramide fonate HOBt = 1-hydroxybenzotriazole TPAP = tetrapropylammonium perruthenate 336 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.

TsCl = p-toluenesulfonyl chloride (tosyl [36] Zarbin, P. H. G.; Princival, J. L.; dos Santos, A. A.; de Oliveira, A. chloride) R. M. J. Braz. Chem. Soc., 2004, 15, 331. [37] Gore, W. E.; Pearce, G. T.; Lanier, G. N.; Simeone, J. B.; Sil- TsNHNH2 = p-toluenesulfonyl hydrazine verst.Rm; Peacock, J. W.; Cuthbert, R. A. Abstr. Am. Chem. Soc., 1974, 65. REFERENCES [38] Blight, M. M.; Wadhams, L. J.; Wenham, M. J. Insect Biochemis- try, 1979, 9, 525. [1] Meinwald, J. Proc. Natl. Acad. Sci. USA, 2003, 100, 14514 [39] Blight, M. M.; Wadhams, L. J.; Wenham, M. J.; King, C. J. For- [2] Mori, K. in The total synthesis of natural products, (ApSimon, J. estry, 1979, 52, 83. Ed.:), Wiley, New York, 1981, Vol. 4. [40] Pignatello, J. J.; Grant, A. J. J. Chem. Ecol., 1983, 9, 615. [3] Mori, K. in The total synthesis of natural products, (ApSimon, J. [41] Ben-Yehuda, S.; Tolasch, T.; Francke, W.; Gries, R.; Gries, G.; Ed.:), Wiley, New York, 1992, Vol. 9. Dunkelblum, E.; Mendel, Z. IOBC-WPRS Bull., 2002, 25, 259. [4] Mori, K. Chem. Commun., 1997, 1153. [42] Zada, A.; Ben-Yehuda, S.; Dunkelblum, E.; Harel, M.; Assael, F., [5] Mori, K. Eur. J. Org. Chem., 1998, 1479. Mendel, Z. J. Chem. Ecol., 2004, 30, 631. [6] Mori, K. Acc. Chem. Res., 2000, 33, 102. [43] Enders, D.; Kipphardt, H.; Fey, P. in Organic Synthesis Coll., Vol. [7] Mori, K. in Chemistry of Pheromones and Other Semiochemicals I, VIII, Wiley, Canada, 1993, pp. 403-414. 2004, Vol. 239, pp. 1-50. [44] Larsson, M.; Andersson, J.; Liu, R.; Högberg, H. E. Tetrahedron [8] Aleu, J.; Bustillo, A. J.; Hernandez-Galan, R., Collado, I. G., Curr. Asymmetry, 2004, 15, 2907. Org. Chem., 2007, 11, 693. [45] Hedenström, E.; Edlund, H.; Lund, S.; Abersten, M.; Persson, D. J. [9] Francke, W.; Toth, M.; Szocs, G.; Krieg, W.; Ernst, H., Busch- Chem. Soc., Perkin Trans. 1., 2002, 1810, mann, E., Z. Naturforsch. C., 1988, 43, 787 [46] Wassgren, A. B.; Bergström, G.; Sierpinski, A.; Anderbrant, O.; [10] Moreira, J. A., Correa, A. G. Tetrahedron Asymmetry, 2003, 14, Högberg, H. E.; Hedenström, E. Naturwissenschaften., 2000, 87, 3787. 24. [11] Ferreira, J. T. B., Zarbin, P. H. G. Bioorg. Med. Chem., 1996, 4, [47] Bergström, G.; Wassgren, A. B.; Anderbrant, O.; Ochieng, S. A.; 381. Ostrand, F.; Hansson, B. S.; Hedenström, E.; Högberg, H. E. Na- [12] Moreira, J. A., Correa, A. G. J. Braz. Chem. Soc., 2000, 11, 614. turwissenschaften., 1998, 85, 244. [13] Zarbin, P. H. G.; Princival, J. L.; de Lima, E. R.; dos Santos, A. A.; [48] Bergström, G.; Wassgren, A. B.; Anderbrant, O.; Fagerhag, J.; Ambrogio, B. G., de Oliveira, A. R. M., Tetrahedron Lett., 2004, Edlund, H.; Hedenström, E.; Högberg, H. E.; Geri, C.; Auger, M. 45, 239. A.; Varama, M.; Hansson, B. S.; Löfqvist, J. Experientia., 1995, [14] Hall, D. R.; Beevor, P. S.; Campion, D. G.; Chamberlain, D. J.; 51, 370. Cork, A.; White, R.; Almestre, A.; Henneberry, T. J.; Nandagopal, [49] Tai, A.; Higashiura, Y.; Kakizaki, M.; Naito, T.; Tanaka, K.; Fujita, V.; Wightman, J. A.; Ranga Rao, G. V. Bull. OILB-SROP., 1993, M.; Sugimura, T.; Hara, H.; Hayashi, N. Biosci. Biotechnol. Bio- 16, 1. chem., 1998, 62, 607. [15] Lamers, Y.; Rusu, G.; Wijnberg, J.; de Groot, A. Tetrahedron, [50] Bekish, A. V.; Prokhorevich, K. N.; Kulinkovich, O. G. Tetra- 2003, 59, 9361. hedron Lett., 2004, 45, 5253. [16] Gijsen, H. J. M.; Kanai, K.; Stork, G. A.; Wijnberg, J.; Orru, R. V. [51] Dandapani, S.; Jeske, M.; Curran, D. P. Proc. Natl. Acad. Sci., A.; Seelen, C.; Vanderkerk, S. M., Degroot, A. Tetrahedron, 1990, USA, 2004, 101, 12008. 46, 7237. [52] Cammaerts, M. C.; Attygalle, A. B.; Evershed, R. P.; Morgan, E. [17] Gries, R.; Gries, G.; Li, J. X.; Maier, C. T.; Lemmon, C. R.; Sles- D. Physiol. Entomol., 1985, 10, 33. sor, K. N. J. Chem. Ecol., 1994, 20, 2501. [53] Brand, J. M. J. Chem. Ecol., 1985, 11, 177. [18] Maier, C. T.; Gries, R., Gries, G. J. Chem. Ecol., 1998, 24, 491. [54] Cammaerts, M. C.; Mori, K. Physiol. Entomol., 1987, 12, 381. [19] Duff, C. M.; Gries, G.; Mori, K.; Shirai, Y.; Seki, M.; Takikawa, [55] Pinyarat, W.; Mori, K. Biosci. Biotechnol. Biochem., 1992, 56, H.; Sheng, T.; Slessor, K. N.; Gries, R.; Maier, C. T.; Ferguson, D. 1673. C. J. Chem. Ecol., 2001, 27, 431. [56] RamirezLucas, P.; Malosse, C.; Ducrot, P. H.; Lettere, M.; Zagatti, [20] Chow, S.; Koenig, W. A.; Kitching, W. Eur. J. Org. Chem., 2004, P. Bioorg. Med. Chem., 1996, 4, 323. 1198. [57] Cho, B. T.; Kim, D. J. Tetrahedron, 2003, 59, 2457. [21] Badioli, M.; Ballini, R.; Bartolacci, M.; Bosica, G.; Torregiani, E.; [58] Baeckström, P.; Bergström, G.; Bjorkling, F.; He, H. Z.; Högberg, Marcantoni, E. J. Org. Chem., 2002, 67, 8938. H. E.; Jacobsson, U.; Lin, G. Q.; Löfqvist, J.; Norin, T.; Wassgren, [22] Millar, J. G.; Knudson, A. E.; McElfresh, J. S.; Gries, R.; Gries, G.; A. B. J. Chem. Ecol., 1989, 15, 61. Davis, J. H. Bioorg. Med. Chem., 1996, 4, 331. [59] Chow, S.; Kitching, W. Tetrahedron Asymmetry, 2002, 13, 779. [23] Passaro, L. C.; Webster, F. X. Synthesis-Stuttgart., 2003, 1187. [60] Suguro, T.; Mori, K. Agric. Biol. Chem., 1979, 43, 869. [24] Francke, W.; Franke, S.; Bergmann, J.; Tolasch, T.; Subchev, M.; [61] Tamaki, Y.; Noguchi, H.; Sugie, H.; Sato, R.; Kariya, A. Appl. Ent. Mircheva, A.; Toshova, T.; Svatos, A.; Kalinova, B.; Karpati, Z.; Zool., 1979, 14, 101. Szocs, G.; Toth, M. Z. Naturforsch. C., 2002, 57, 739. [62] Pomonis, J. G.; Hammack, L.; Hakk, H. J. Chem. Ecol., 1993, 19, [25] Miyashita, M.; Yoshikoshi, A.; Grieco, P.A. J. Org. Chem., 1977, 985. 42, 3772. [63] Furukawa, A.; Shibata, C.; Mori, K. Biosci. Biotechnol. Biochem., [26] Wakamura, S.; Arakaki, N.; Yamamoto, M.; Hiradate, S.; Yasui, 2002, 66, 1164. H.; Yasuda, T.; Ando, T. Tetrahedron Lett., 2001, 42, 687. [64] Mori, K.; Ohtaki, T.; Ohrui, H.; Berkebile, D. R.; Carlson, D. A. [27] Fernandes, R. A.; Kumar, P. Tetrahedron, 2002, 58, 6685. Eur. J. Org. Chem., 2004, 1089. [28] Gries, R.; Holden, D.; Gries, G.; Wimalaratne, P. D. C.; Slessor, K. [65] Mori, K.; Ohtaki, T.; Ohrui, H.; Berkebile, D. R.; Carlson, D. A. N.; Saunders, C. Naturwissenschaften., 1997, 84, 219. Biosci. Biotechnol. Biochem., 2004, 68, 1768. [29] Muto, S.; Mori, K. Eur. J. Org. Chem., 2003, 1300. [66] Shirai, Y.; Seki, M.; Mori, K. Eur. J. Org. Chem., 1999, 3139. [30] Wimalaratne, P. D. C.; Slessor, K. N. J. Chem. Ecol., 2004, 30, [67] Hillbur, Y.; Anderson, P.; Arn, H.; Bengtsson, M.; Löfqvist, J.; 1225. Biddle, A. J.; Smitt, O.; Högberg, H. E.; Plass, E.; Franke, S.; Fran- [31] Muto, S.; Mori, K. Biosci. Biotechnol., Biochem., 2003, 67, 1559. cke, W. Naturwissenschaften., 1999, 86, 292. [32] Perez, A. L.; Campos, Y.; Chinchilla, C. M.; Oehlschlager, A. C.; [68] Guss, P.L.; Tumlinson, J.H.; Sonnet, P.E.; Proveaux, A.T. J. Chem. Gries, G.; Gries, R.; GiblinDavis, R. M.; Castrillo, G.; Pena, J. E.; Ecol., 1982, 8, 545. Duncan, R. E.; Gonzalez, L. M.; Pierce, H. D.; McDonald, R.: An- [69] Tanaka, Y.; Honda, H.; Ohsawa, K.; Yamamoto, I. J. Pest. Sci., drade, R. J. Chem. Ecol., 1997, 23, 869. 1986, 11, 49. [33] Giblin-Davis, R. M.; Gries, R.; Crespi, B.; Robertson, L. N.; Hara, [70] Tanaka, Y.; Honda, H.; Ohsawa, K., Yamamoto, I., J. Pest. Sci., A. H.; Gries, G.; O'Brien, C. W.; Pierce, H. D. J. Chem. Ecol., 1989, 14, 197. 2000, 26, 2763. [71] Suzuki, T. Agric. Biol. Chem., 1981, 45, 1357. [34] Baraldi, P. T.; Zarbin, P. H. G.; Vieira, P. C.; Correa, A. G., Tetra- [72] Suzuki, T. Agric. Biol. Chem., 1981, 45, 2641. hedron Asymmetry, 2002, 13, 621. [73] Mori, K.; Kuwahara, S., Ueda, H., Tetrahedron, 1983, 39, 2439. [35] Dhotare, B.; Salaskar, A.; Chattopadhyay, A. Synthesis-Stuttgart., [74] Levinson, H. Z.; Mori, K. Naturwissenschaften., 1983, 70, 190. 2003, 2571. Synthesis of Pheromones Current Organic Chemistry, 2009, Vol. 13, No. 4 337

[75] Suzuki, T.; Kozaki, J.; Sugawara, R.; Mori, K. Appl. Ent. Zool., [112] Wheeler, J.W.; Evans, S.L.; Blum, M.S.; Velthius, H.H.V.; 1984, 19, 15. Camargo, J. Tetrahedron Lett., 1976, 4029. [76] Ismuratov, G. Y.; Yakovleva, M. P.; Galyautdinova, A.V.; Tolsti- [113] Tumlinson, J.H.; Klein, M.G.; Doolittle, R.E.; Ladd, T.L.; kov, G.A. Chem. Nat. Compd., 2003, 39, 31. Proveaux, A.T. Science, 1977, 197, 789. [77] Odinokov, V.N.; Akhmetova, V.R.; Khasanov, K.D.; Abduvakha- [114] Zarbin, P.H.G.; Oliveira, A.R.M.; Simonelli, F.; Villar, J.; Delay, bov, A.A.; Tolstikov, G.A. Khimiya Prirodnykh Soedinenii., 1991, O. Tetrahedron Lett., 2004, 45, 7399. 568. [115] Zarbin, P.H.G.; de Oliveira, A.R.M.; Delay, C.E. Tetrahedron [78] Leal, W. S.; Kuwahara, Y.; Suzuki, T.; Kurosa, K. Naturwissen- Lett., 2003, 44, 6849. schaften., 1989, 76, 332. [116] Zarbin, P.H.G.; Arrigoni, E.D.; Reckziegel, A.; Moreira, J.A.; [79] Shimizu, N.; Mori, N.; Kuwahara, Y. Biosci. Biotechnol. Biochem., Baraldi, P.T.; Vieira, P.C. J. Chem. Ecol., 2003, 29, 377. 2001, 65, 1724. [117] Kang, S.K.; Shin, D.S.; Lee, J.O.; Goh, H.G. Bull. Korean Chem. [80] Noguchi, S.; Mori, N.; Kurosa, K.; Kuwahara, Y. Appl. Ent. Zool., Soc., 1986, 7, 444. 1998, 33, 53. [118] Laurence, B.R.; Pickett, J.A. J. Chem. Soc. Chem. Commun., 1982, [81] Shimizu, N.; Mori, N.; Kuwahara, Y. Biosci. Biotechnol. Biochem., 59. 2003, 67, 1732. [119] Sun, B.; Peng, L.Z.; Chen, X.S.; Li, Y.L.; Li, Y. Chin. Chem. Lett., [82] Guss, P.L.; Tumlinson, J.H.; Sonnet, P.E.; McLaughlin, J.R. J. 2004, 15, 1177. Chem. Ecol., 1983, 9, 1363. [120] Leal, W.S.; Kuwahara, S.; Ono, M.; Kubota, S. Bioorg. Med. [83] Chuman, T.; Guss, P.L.; Doolittle, R.E.; McLaughlin, J.R.; Krysan, Chem., 1996, 4, 315. J.L.; Schalk, J. M.; Tumlinson, J. H. J. Chem. Ecol., 1987, 13, [121] Clososki, G.C.; Ricci, L.C.; Costa, C.E.; Comasseto, J. V. J. Braz. 1601. Chem. Soc., 2004, 15, 809. [84] Gries, G.; Slessor, K.N.; Gries, R.; Khaskin, G.; Wimalaratne, [122] Light, D.M.; Birch, M.C. Naturwissenschaften., 1979, 66, 159. P.D.C.; Gray, T. G.; Grant, G. G.; Tracey, A. S.; Hulme, M. J. [123] Ceschi, M.A.; Petzhold, C.; Schenato, R.A. J. Braz. Chem. Soc., Chem. Ecol., 1997, 23, 19. 2003, 14, 759. [85] Gries, R.; Schaefer, P. W.; Yoo, H.J.S.; Greaves, M.; Gries, G. [124] Arai, T.; Sugie, H.; Hiradate, S.; Kuwahara, S.; Itagaki, N.; Naka- Can. Entomol., 2005, 137, 471. hata, T. J. Chem. Ecol. 2003, 29, 2213. [86] El-Sayed, A.M.; Gibb, A.R.; Suckling, D.M.; Bunn, B.; Fielder, S.; [125] Nakahata, T.; Itagaki, N.; Arai, T.; Sugie, H.; Kuwahara, S. Biosci. Comeskey, D.; Manning, L.A.; Foster, S.P.; Morris, B.D.; Ando, Biotechnol. Biochem., 2003, 67, 2627. T.; Mori, K. J. Chem. Ecol., 2005, 31, 621. [126] Bierlleonhardt, B.A.; Moreno, D.S.; Schwarz, M.; Fargerlund, J.; [87] Jury, J.C.; Fielder, S.; Vigneswaran, M. Tetrahedron Lett., 2003, Plimmer, J.R. Tetrahedron Lett., 1981, 22, 389. 44, 27. [127] Passaro, L.C.; Webster, F.X. J. Agric. Food Chem., 2004, 52, 2896 [88] Uenishi, J.; Kawahama, R.; Izaki, Y.; Yonemitsu, O. Tetrahedron, [128] Tumlinson, J.H.; Hardee, D.D.; Gueldner, R.C.; Thompson, A.C.; 2000, 56, 3493. Hedin, P.A. Science, 1969, 166, 1010. [89] Comeskey, D.J.; Bunn, B.J.; Fielder, S. Tetrahedron Lett., 2004, [129] Booth, D.C.; Phillips, T.W.; Claesson, A.; Silverstein, R.M.; 45, 7651. Lanier, G.N.; West, J. R. J. Chem. Ecol., 1983, 9, 1. [90] Burkholder, W. E. In Pheromone Research with Stored-Product [130] Phillips, T.W.; West, J.R.; Foltz, J.L.; Silverstein, R.M.; Lanier, G. Coleoptera., Academic Press, New York., 1970. N. J. Chem. Ecol., 1984, 10, 1417. [91] Chuman, T.; Kato, K., Noguchi, M., Agric. Biol. Chem., 1979, 43, [131] Francke, W.; Pan, M. L.; Konig, W. A.; Mori, K.; Puapoomchare- 2005. on, P.; Heuer, H.; Vite, J. P. Naturwissenschaften., 1987, 74, 343. [92] Chuman, T.; Kohno, M.; Kato, K., Noguchi, M. Tetrahedron Lett., [132] Bernard, A.M.; Frongia, A.; Secci, F.; Delogu, G.; Ollivier, J.; 1979, 2361. Piras, P.P.; Salaun, J. Tetrahedron., 2003, 59, 9433. [93] Ono, M.; Onishi, I.; Chuman, T.; Kohno, M., Kato, K. Agric. Biol. [133] Alizadeh, B.H.; Kuwahara, S.; Leal, W.S.; Men, H.C. Biosci. Bio- Chem., 1980, 44, 2259. technol. Biochem., 2002, 66, 1415. [94] Mori, K.; Nomi, H.; Chuman, T.; Kohno, M.; Kato, K.; Noguchi, [134] Kulkarni, Y.S.; Niwa, M.; Ron, E.; Snider, B. B. J. Org. Chem., M. Tetrahedron., 1982, 38, 3705. 1987, 52, 1568. [95] Mori, M.; Chuman, T.; Kohno, M.; Kato, K.; Noguchi, M.; Nomi, [135] Zhang, Q.H.; Chauhan, K.R.; Erbe, E.F.; Vellore, A.R.; Aldrich, H.; Mori, K. Tetrahedron Lett., 1982, 23, 667. J.R. J. Chem. Ecol., 2004, 30, 1849. [96] Zlokazov, M.V.; Veselovsky, V.V. Russ. Chem. Bull., 2002, 51, [136] Chauhan, K.R.; Zhang, Q.H.; Aldrich, J.R. Tetrahedron Lett., 2004, 1600. 45, 3339. [97] Zlokazov, M.V.; Veselovsky, V.V. Russ. Chem. Bull., 2000, 49, [137] Birkett, M.A.; Pickett, J.A. Phytochemistry., 2003, 62, 651. 154. [138] Dickens, J.C.; Oliver, J.E.; Hollister, B.; Davis, J.C.; Klun, J.A. J. [98] Tolasch, T.; Borgemeister, C.; Masuda, Y.; Fujita, K.; Mori, K.; Exp. Biol., 2002, 205, 1925. Francke, W. Abstracts of papers, 19th Annual Meeting of Interna- [139] Oliver, J.E.; Dickens, J.C.; Glass, T.E. Tetrahedron Lett., 2002, 43, tional Chemical Ecology, Hamburg Germany, 2002, 147. 2641. [99] Masuda, Y.; Fujita, K.; Mori, K. Biosci. Biotechnol. Biochem., [140] Baker, R.; Herbert, R.H.; Parton, A.H. J. Chem. Soc. Chem. Com- 2003, 67, 1744. mun., 1982, 601. [100] Brand, J.M.; Duffield, R.M.; MacConnell, J.G.; Blum, M.S.; Fales, [141] Baker, R.; Herbert, R.H. J. Chem. Soc. Perkin Trans. 1., 1987, H.M. Science, 1973, 179, 388 1123. [101] Fernandes, L.; Bortoluzzi, A.J.; Sá, M.M. Tetrahedron., 2004, 60, [142] Hao, J.L.; Forsyth, C.J. Tetrahedron Lett., 2002, 43, 1. 9983. [143] Silverstein, R.M.; Brownlee, R.G.; Bellas, T.E.; Wood, D.L.; [102] Schulz, S.; Nishida, R. Bioorg. Med. Chem., 1996, 4, 341. Browne, L.E. Science, 1968, 159, 889. [103] Nishida, R.; Schulz, S.; Kim, C.S.; Fukami, H.; Kuwahara, Y.; [144] Bedard, W.D.; Tilden, P.E.; Wood, D.L.; Silverstein, R.M.; Brown- Honda, K.; Hayashi, N. J. Chem. Ecol., 1996, 22, 949. lee, R.G.; Rodin, J.O. Science, 1969, 164, 1284. [104] Stritzke, K.; Schulz, S.; Nishida, R. Eur. J. Org. Chem., 2002, [145] Wood, D.L.; Browne, L.E.; Ewing, B.; Lindahl, K.; Bedard, W.D.; 3884. Tilden, P. E.; Mori, K.; Pitman, G.B.; Hughes, P.R. Science, 1976, [105] Yarger, R.G.; Silverstein, R.M.; Burkholder, W.E. J. Chem. Ecol., 192, 896. 1975, 1, 323. [146] Vite, J.P.; Billings, R.F.; Ware, C.W.; Mori, K. Naturwissenschaf- [106] Ravid, U.; Smith, L.R.; Silverstein, R.M. Tetrahedron, 1978, 34, ten., 1985, 72, 99. 1449. [147] Mayer, S.F.; Mang, H.; Steinreiber, A.; Saf, R.; Faber, K. Can. J. [107] Arceo, E.; Odriozola, J.M.; Garcia, J.M.; Gonzalez, A.; Gil, P. Chem., 2002, 80, 362. Tetrahedron Asymmetry, 2003, 14, 1617. [148] Francke, W.; Schroder, F.; Philipp, P.; Meyer, H.; Sinnwell, V.; [108] Cossé, A.A.; Bartelt, R.J.; James, D.G.; Petroski, R.J. J. Chem. Gries, G. Bioorg. Med. Chem., 1996, 4, 363. Ecol., 2001, 27, 1841. [149] Kumar, D.N.; Rao, B.V. Tetrahedron Lett., 2004, 45, 2227. [109] James, D.G.; Petroski, R.J.; Cossé, A.A.; Zilkowski, B.W.; Bartelt, [150] Johnston, B.D.; Oehlschlager, A.C. J. Org. Chem., 1982, 47, 5384. R.J. J. Chem. Ecol., 2003, 29, 2189. [151] Kinzer, G.W.; Fentiman, A.F.; Page, T.F.; Foltz, R.L.; Vite, J.P.; [110] Shibata, C.; Mori, K. Eur. J. Org. Chem., 2004, 1083. Pitman, G.B. Nature, 1969, 221, 477. [111] Posner, G. H.; Johnson, N. J. Org. Chem., 1994, 59, 7855. [152] Mori, K. Tetrahedron, 1975, 31, 1381. 338 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.

[153] Chenêvert, R.; Caron, D. Tetrahedron Asymmetry, 2002, 13, 339 [160] Johnston, B.D.; Slessor, K.N.; Oehlschlager, A.C. J. Org. Chem., [154] Yang, X.B.; Luo, S.J.; Hua, C.W.; Zhai, H.B. Tetrahedron, 2003, 1985, 50, 114. 59, 8551. [161] Skattebol, L.; Stenstrom, Y. Acta Chem. Scand. B., 1985, 39, 291 [155] Nakashima, T. 2nd Asia-Pacific Conference on Chemical Ecology [162] Asai, N.; Fusetani, N.; Matsunaga, S.; Sasaki, J. Tetrahedron, 2001, Penang, Malaysia, Abstract No. 27. 2000, 56, 9895. [156] Marukawa, K.; Mori, K. Chem. Lett., 2002, 40. [163] Masuda, Y.; Yoshida, M.; Mori, K. Biosci. Biotechnol. Biochem., [157] Marukawa, K.; Mori, K. Eur. J. Org. Chem., 2002, 3974. 2002, 66, 1531. [158] MacConnell, J.G.; Borden, J.H.; Silverstein, R.M.; Stokkink, E. J. [164] Garner, P.; Park, J. M. J. Org. Chem., 1987, 52, 2361. Chem. Ecol., 1977, 3, 549. [165] Garner, P.; Park, J. M. Malecki, E. J. Org. Chem., 1988, 53, 4395. [159] Alibés, R.; de March, P.; Figueredo, M.; Font, J.; Racamonde, M.; Parella, T. Org. Lett., 2004, 6, 1449.