Semiochemistry of Pentatomoidea 689
also has successfully invaded Europe, and now is established in Switzerland, France, Italy, Greece, and
Hungary (Haye et al. 2015). It already has caused significant economic damage to agriculture in >12 of
the United States, in addition to its nuisance status as an invader of homes and other buildings for over-
wintering (Northeastern IPM Center 2015). The species is native to and widespread in northeastern Asia;
in its native and introduced ranges, H. halys feeds on a wide variety of fruit crops (Lee et al. 2013), and,
not surprisingly, it has become a significant agricultural pest in the United States (Leskey et al. 2012a,b).
15.2.9.1 Aggregation Pheromone
Khrimian et al. (2014a) identified a male-produced aggregation pheromone of H. halys as a 3.5:1 mix-
ture of two epoxides, (3S,6S,7R,10S)-10,11-epoxy-1-bisabolen-3-ol ( 37 ) and (3R,6S,7R,10S)-10,11-epoxy-
1-bisabolen-3-ol ( 38 ) (Figure 15.7). The basic skeletons of the pheromone stereoisomers first were
identified by comparison to spectral data from mixtures of the stereoisomers generated during the iden-
tification of the pheromone of another stink bug, Murgantia histrionica (Zahn et al. 2008, vide infra).
The specific stereoisomers produced by H. halys then were identified by synthesis of stereoisomeric
libraries of 10,11-epoxy-1-bisabolen-3-ols and screening those on two enantioselective gas chromatog-
raphy columns (Khrimian et al. 2014a,b). A novel and straightforward route to all stereoisomers of
1,10-bisaboladien-3-ol and 10,11-epoxy-1-bisabolen-3-ol was developed (Khrimian et al. 2014a; Figure
15.7) via the rhodium-catalyzed asymmetric addition of trimethylaluminum (Siewert et al. 2007) to
diastereomeric mixtures of cyclohex-2-enones 39 and 48. Ketones 39 and 48 were synthesized from
(R)- and (S)-citronellals, respectively, using 1,4-conjugate addition to methyl vinyl ketone mediated by
diethylamino(trimethyl)silane, followed by intramolecular cyclization with potassium hydroxide cata-
lyzed by tetrabutylammonium hydroxide (Hagiwara et al. 2002). Figure 15.7.
Addition of trimethylaluminum to ketone 39 in the presence of chloro(1,5-cyclooctadiene)rhodium(I)
dimer ([Rh(cod)Cl] 2 ) and (R)-BINAP (Figure 15.7, top) yielded stereoisomers 40 and 41 as major and
minor products, respectively. The selective formation was attributed to relatively facile delivery of
the methyl group to the sterically less hindered bottom face of the (6S,7R)-stereoisomer of 39 to give
(3S,6S,7R)-1,10-bisaboladien-3-ol ( 40 ), whereas the reaction with sterically less favorable (6R,7R)- 39 to
give (3S,6R,7R)-stereoisomer 41 proceeded in low yield and modest diastereoselectivity. Alcohol 40 was
stereoselectively dihydroxylated with AD-mix-β, and the resulting triol 42 was converted to epoxybis-
abolenol 37 , the main pheromone component of H. halys (Khrimian et al. 2014a) and M. histrionica
(Khrimian et al. 2014b). Dihydroxylation of 40 with AD-m ix-α, followed by cyclization of intermediate
triol 43 , provided epoxybisabolenol 44 , the minor aggregation pheromone component of M. histrionica
(discussed below).
Addition of trimethylaluminum to 39 in the presence of [Rh(cod)Cl] 2 and (S)-BINAP (Figure 15.7,
middle) led to the stereoisomers 45 and 46 , from predominant delivery of the methyl group from the
top face, with (6R,7R)- 39 being sterically more favorable than (6S,7R)- 39. The minor trans-stereoisomer
46 was dihydroxylated with AD-mix-β and converted as described above to epoxybisabolenol 38 that
matched a minor component of the H. halys pheromone blend.
The stereochemistries of the addition of trimethylaluminum to the ketone 48 (Figure 15.7, bottom)
with the (7S)-configuration in the presence of [Rh(cod)Cl] 2 and (S)- and (R)-BINAP were governed
essentially by the same rules as described above for the (7R)-ketone 39. One notable application in this
series is the synthesis of (3R,6R,7S)-1,10-bisaboladien-3-ol (= zingiberenol) ( 50 ), which has been identi-
fied as a sex pheromone component of the rice stink bug, Oebalus poecilus (de Oliveira et al. 2013), but
the compound’s synthesis was not described.
The assignments of the relative and absolute configurations of the stereoisomeric 1,10- bisaboladien-3-ols
and 10,11-epoxy-1-bisabolen-3-ols were carried out by single-crystal X-ray crystallography of underiva-
tized (3R,6S,7R,10S)- and (3S,6R,7R,10S)- triols and correlations with stereodefined 1,3,10-bisabolatrienes
(= zingiberenes) and 1,3(15),10-bisabolatrienes (= sesquiphellandrenes) (Khrimian et al. 2014a,b). Thus,
1,10-bisaboladien-3-ols and 10,11-epoxy-1-bisabolen-3-ols, having lower thin layer chromatography
Rf values and longer GC retention times (38, 41, 46 , and 49 ), were found to have the trans relative
configuration. Conversely, the less polar, shorter retention time stereoisomers 37, 4 0, 44 , 45 , and
50 had the cis configuration.