Catalytic, enantioselective synthesis of 1,2-anti-diols by asymmetric ring-opening/cross-metathesis

Article abstract of DOI:10.1002/anie.201310767

An enantioselective method for the synthesis of 1,2-anti-diols has been developed. A cyclometalated chiral-at-ruthenium complex catalyzes the asymmetric ring-opening/cross-metathesis of dioxygenated cyclobutenes, thus resulting in functionally rich synthetic building blocks. Syntheses of the insect pheromone (+)-endo-brevicomin and monosaccharide ribose demonstrate the synthetic utility of the 1,2-anti-diol fragments generated in the title reaction. Rather fetching: Chiral vicinal diols are found in natural products and ligands used for asymmetric catalysis. The enantioselective ring-opening/cross-metathesis of disubstituted cyclobutenes has been carried out with an enantiopure ruthenium metathesis catalyst to afford 1,2-anti-diols with high enantiopurity. The synthetic versatility of the products was demonstrated in the synthesis of insect pheromone (+)-endo-brevicomin and a monosaccharide ribose.

Full text of DOI:10.1002/anie.201310767

Angewandte
Chemie
DOI: 10.1002/anie.201310767
Asymmetric Catalysis
Catalytic, Enantioselective Synthesis of 1,2-anti-Diols by Asymmetric
Ring-Opening/Cross-Metathesis**
John Hartung and Robert H. Grubbs*
Abstract: An enantioselective method for the synthesis of 1,2-
anti-diols has been developed. A cyclometalated chiral-at-
ruthenium complex catalyzes the asymmetric ring-opening/
cross-metathesis of dioxygenated cyclobutenes, thus resulting
in functionally rich synthetic building blocks. Syntheses of the
insect pheromone (+)-endo-brevicomin and monosaccharide
ribose demonstrate the synthetic utility of the 1,2-anti-diol
fragments generated in the title reaction.
Scheme 1. AROCM reaction to afford highly enantioenriched 1,2-anti-
T
he formation of multiple stereocenters in a single catalytic
diols.
transformation is a powerful approach to the synthesis of
stereochemically complex targets. While the development of
such a transformation must overcome the challenge of
simultaneously controlling diastereo- and enantioselectivity,
the end result can reduce the step count of a synthesis and
improve its atom economy. One commonly encountered
motif is the vicinal diol, which is found in natural products and
ligands for asymmetric transformations. While the problem of
introducing vicinal diols in high enantiopurity has largely
been solved by the Sharpless asymmetric dihydroxylation
(AD), the formation of 1,2-anti-diols remains challenging
because of the low enantioselectivity observed in the AD of
cis-1,2-disubstituted alkenes.[1] Accordingly, a number of
methods have been developed for the enantioselective
formation of 1,2-anti diols, including asymmetric epoxida-
tion/hydrolysis,[2] glycolate aldol,[3] iterative cross-metathesis/
allylic substitution,[4] nucleophilic addition to aldehydes,[5]
desymmetrizing monofunctionalization,[6] and allene hydro-
boration/aldehyde allylation.[7] In contrast to many of these
methods, an asymmetric ring-opening/cross-metathesis
(AROCM) approach (Scheme 1) would consolidate the
transformation into a single step and generate a differentiated
1,5-diene fragment in a convergent manner.
diastereo-[9] and enantioselectivity.[10] Although the ROCM of
cyclobutenes to form racemic products has been demonstra-
ted,[9f,11] previous studies of their AROCM reactions have
afforded products with low enantioenrichment.[10i]
It was envisioned that the desymmetrization of suitably
substituted meso-cyclobutenes by AROCM would afford the
1,2-anti-diol motif in perfect anti diastereoselectivity and
potentially high enantioselectivity upon application of
a newly developed cyclometalated metathesis catalyst (1,
Scheme 1).[12] The resultant 1,5-diene would be a versatile
synthetic intermediate because of the differential reactivity of
the two alkenes, thus paving the way for further chemo-
selective transformations. Herein, we report the successful
application of 1 to afford highly enantioenriched 1,2-anti-diols
and demonstrate the versatility of these products in the
synthesis of the insect pheromone (+)-endo-brevicomin and
a derivative of the monosaccharide l-ribose. Pest control
strategies utilizing insect pheromones have become a promis-
ing alternative to the application of broad-spectrum insecti-
cides, thus underscoring the importance of rapid synthetic
routes to (+)-endo-brevicomin and related bioactive com-
pounds.[13,14]
Initial attempts to form 1,2-anti-diols were carried out
with 1, allyl acetate (3), and cis-3,4-dibenzyloxycyclobutene
(2; Table 1), which was synthesized by substitution of
commercially available cis-3,4-dichlorocyclobutene with
sodium phenylmethanolate.[15] The solvent had no effect on
the selectivity of the AROCM reaction except for slightly
diminished enantioselectivity in CH2Cl2 (entry 1). The yield
was highest in THF (entry 4). The effect of stoichiometry in
AROCM has been explored for a number of catalysts.[10b,i,16]
In the current study, an excess of the terminal olefin was
optimal (7 equiv, entry 4). As the number of equivalents of
terminal olefin were reduced, the yield of the reaction fell, yet
a modest yield of 29% could be obtained with 1.2 equivalents
of 3. No bis(cross-product) was observed. Reducing the
concentration also resulted in lower yield, thus leading to the
optimal reaction conditions, which involve 7 equivalents of 3
À
Asymmetric olefin metathesis is a powerful C C bond-
forming reaction and has enabled the synthesis of stereo-
chemically complex bioactive compounds.[8] Advances in
stereoselective olefin metathesis have resulted in the devel-
opment of catalysts capable of forming products with high
[*] Dr. J. Hartung, Prof. R. H. Grubbs
Division of Chemistry and Chemical Engineering
California Institute of Technology, Pasadena, CA 91125 (USA)
E-mail: rhg@caltech.edu
[**] This work was financially supported by the NIH (5R01GM031332-27
to R.H.G.) and the NSF (CHE-1048404 to R.H.G.). We thank
Materia, Inc. for donation of metathesis catalysts and Dr. Jeffrey
Cannon, Dr. Bill Morandi, and Zach K. Wickens for helpful
discussion.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201310767.
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Table 1: Optimization of the AROCM of cyclobutene 2 with 3.
Table 2: Scope of the AROCM reaction with respect to cyclobutene
substitution.[a]
Entry
Equiv 3
Conc [m]
Solvent
Yield[a]
Z
Z
[%][a]
ee [%][b]
Yield
[%][b]
Z
ee [%][d]
R1
R2
Product
[%][c]
Z
E
1
2
3
4
5
6
7
8
9
7
7
7
7
5
3
1.2
7
7
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.3
0.1
CH2Cl2
benzene
toluene
THF
THF
THF
THF
THF
THF
35
49
52
79
71
63
29
72
43
83
84
84
85
84
85
87
85
85
93
95
95
95
96
96
97
95
95
TBS
OH
7a
7b
7c
7d
66
67
88
99
n.d.
67
H
OBz
OH
75
91
[a] Determined by GC. [b] Determined by chiral SFC.
Bz
iPr
69
75
96
82
OBz
<5
n.d.
n.d.
n.d.
in THF at a concentration of 0.5m, with respect to 2, with
1 mol% 1 for a reaction time of 1.5 hours. Notably, although
alternative solvents or stoichiometry negatively impacted
reaction efficiency, the diastereo- and enantioselectivity
remained consistently high, thus demonstrating the robust-
ness of the reaction.
[a] Used 0.1 mmol cyclobutene and 0.7 mmol terminal olefin. [b] Com-
bined yield for the isolated E and Z products. [c] Determined by 500 MHz
1H NMR analysis of the crude reaction mixture. [d] Determined by chiral
SFC. Bz=benzoyl, TBS=tert-butyldimethylsilyl.
While the synthesis of a 1,2-anti-alkoxy motif had been
demonstrated, inclusion of alternative protecting groups on
the diol motif strengthens the synthetic protocol. These
modifications allow a synthetic sequence to be designed such
that the feasibility of removing the protecting groups in the
presence of other functionality can be taken into account.
Moreover, modulation of the size and electronics of the
groups on the cyclobutene and terminal olefin reactants
would provide a better understanding of the factors contri-
buting to selectivity.
from each other by flash or thin-layer chromatography in all
cases except for that of 7i.
We next explored the synthetic utility of the 1,2-anti-diol
fragments produced in the AROCM reaction. Cyclic ketals,
derived from the 1,2-anti-diol motif, feature prominently in
the structures of several natural products.[19] Accordingly, we
targeted this structure in the context of a synthesis of the
insect pheromone (+)-endo-brevicomin (11, Scheme 2).[20]
A complement of commonly used hydroxy protecting
groups were tolerated on the cyclobutene and terminal olefin
reactants,[17] but enantio- and diastereoselectivity were
affected by the choice of substituents (Tables 2 and 3). The
increased bulkiness of the tert-butyldimethylsilyl ether
resulted in improved Z selectivity and remarkable enantio-
selectivity (7a, Table 2), while hydroxy and benzoate groups
on the cyclobutene reactant led to Z products with 91% and
96% ee, respectively. The same enantioinduction was
observed in the products 7a and 7b. Isopropoxy substituents
on the cyclobutene resulted in abrogation of the catalyst
activity, presumably because of the formation of a stable
chelating complex.[18]
High enantioselectivities were obtained with a wide range
of terminal olefins. Among the O-protecting groups surveyed
(7e–h; Table 3), the tert-butyldimethylsilyl group resulted in
high enantioselectivity (7g), but the more electron-withdraw-
ing benzoate ester was optimal, thus resulting in the highest
enantioselectivity (7 f). Terminal olefins bearing alkyl sub-
stituents resulted in higher diastereoselectivity and yield with
similar levels of enantioselectivity (7i, j). The chiral allylation
reagent 7k was synthesized in 91% ee, thus affording a func-
tionally useful building block. Z and E isomers were isolable
Scheme 2. Enantioselective synthesis of (+)-endo-brevicomin. a) 1
(1 mol%), rac-8 (7 equiv), THF, 238C, 85% yield, 91% Z, 1:1 d.r.,
95% ee. b) Dess–Martin periodinane (2 equiv), 0-238C, 88% yield.
c) H2 (1 atm), Pd/C (10%), MeOH/aq. 1n HCl, 67% yield.
(+)-endo-Brevicomin is a male produced component of
the attractive pheromone system of Dendroctonus frontalis
(southern pine beetle),[19a] a tree-killing insect found in
southern North and Central America. It was envisioned that
AROCM of 2 with 4-penten-2-ol would set the relative and
absolute stereochemistry in the synthesis of (+)-endo-brevi-
comin.
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Table 3: Scope of the AROCM reaction with respect to the terminal
olefin.[a]
Scheme 3. Enantioselective synthesis of an l-ribose derivative. a) OsO4
(5 mol%), K3Fe(CN)6, K2CO3, tBuOH/water (1:1) , 66% yield, 9:1 d.r.
b) O3 then Me2S. c) HCl in MeOH (anh.), 47% yield (over two steps).
Yield
Z
ee [%][d]
R2
Product
[%][b] [%][c]
Z
E
into useful monosaccharides (Scheme 3). Dihydroxylation of
(Z)-7 f catalyzed by OsO4 afforded a 66% yield of the
differentially protected pentanol 12 in 9:1 d.r.[23] Ozonolysis of
the remaining double bond afforded the differentially pro-
tected l-ribose lactol, which was isolated as the methyl
glycoside 13 in 47% yield over two steps.[24] It is hypothesized
that a broader collection of monosaccharides will be acces-
sible from the AROCM products by the modification of this
synthetic sequence.
In conclusion, the highly enantioselective synthesis of 1,2-
anti-diols was accomplished by the application of catalyst 1 to
the AROCM of cis-dioxygenated cyclobutenes. The reaction
is robust, tolerating modifications in reaction conditions and
substitution on the reactants. Enantioenrichment of the major
Z isomers was exceptionally high, ranging from 89–99% ee.
The rapid synthesis of insect pheromone (+)-endo-brevico-
min afforded the natural product in 95% ee. A 1,5-diene
generated by the AROCM reaction was chemoselectively
functionalized to afford the ribose derivative 13, thus
demonstrating the utility of the building blocks afforded by
the title reaction.
OH
7e 62
89
88
87
86
90
90
93 86
OBz
7 f 61
7g 68[e]
7h 64
97 88
89 77
91 n.d.
93 79
92 84
OTBS
OBn
4-MeOPh
CH2C(O)CH3
BPin
7i
7j
76
65
7k 50
n.d.[f] 91 n.d.
[a] Used 0.1 mmol cyclobutene and 0.7 mmol terminal olefin. [b] Com-
bined yield of the isolated E and Z products. [c] Determined by 500 MHz
1H NMR analysis of the crude reaction mixture. [d] Determined by chiral
SFC. [e] Yield determined after derivatization to 7e. [f] Not determined
because of instability of the E product. Pin=pinacol.
Experimental Section
In a glovebox, the cyclobutene 2 (26.6 mg, 0.1 mmol) and allyl
benzoate (113 mg, 0.7 mmol, 7 equiv) were dissolved in 0.15 mLTHF.
A stock solution (50 mL; 0.02m in THF) of the catalyst 1 was added to
this solution. The reaction vial was capped, the reaction mixture
stirred for 1.5 h, and then quenched with an excess of ethyl vinyl ether
outside of the glove box. The reaction mixture was concentrated and
subjected to flash chromatography to afford the desired AROCM
product [7 f, 25.9 mg, 61% yield, 88:12 Z/E, 97% ee (Z product),
88% ee (E product)].
An expedient three-step synthesis of (+)-endo-brevico-
min was accomplished by the AROCM of 2 with rac-8 to
afford 9 (91% Z) in 85% yield as an inconsequential mixture
of diastereomers (Scheme 2).[21] The mixture of epimeric
alcohols was cleanly oxidized to the desired ketone by Dess–
Martin periodinane in 88% yield. (Z)-10 was obtained in
95% ee, thus indicating high enantioselectivity in the
AROCM reaction. Hydrogenation of (Z)-10 in acidic meth-
anol resulted in concomitant reduction of the alkenes, hydro-
genolysis of the benzyl groups, and cyclization to form
(+)-endo-brevicomin in 67% yield in a one-pot transforma-
tion.[22]
Received: December 11, 2013
Published online: February 19, 2014
Keywords: alcohols · asymmetric catalysis · metathesis ·
.
pheromones · ruthenium
It was envisioned that the synthetic utility of the 1,5-
dienes produced in the AROCM of cyclobutenes could be
further underscored by chemoselective functionalization of
the two alkenes. For example, the introduction of additional
hydroxy groups would enable the rapid synthesis of mono-
saccharides. In this fashion, a succinct and highly enantiose-
lective synthesis of monosaccharides could function as
a robust route to starting materials for complex polysaccha-
rides.
[1] H. C. Kolb, M. S. VanNieuwenhze, K. B. Sharpless, Chem. Rev.
1994, 94, 2483 – 2547.
[2] a) S. M. Lim, N. Hill, A. G. Myers, J. Am. Chem. Soc. 2009, 131,
5763 – 5765; b) L. Albrecht, H. Jiang, G. Dickmeiss, B.
Gschwend, S. G. Hansen, K. A. Jorgensen, J. Am. Chem. Soc.
2010, 132, 9188 – 9196.
[3] a) T. Mukaiyama, N. Iwasawa, Chem. Lett. 1984, 753 – 756;
b) D. A. Evans, J. R. Gage, J. L. Leighton, A. S. Kim, J. Org.
Chem. 1992, 57, 1961 – 1963; c) W. Notz, B. List, J. Am. Chem.
Soc. 2000, 122, 7386 – 7387; d) M. T. Crimmins, P. J. McDougall,
Org. Lett. 2003, 5, 591 – 594; e) A. B. Northrup, D. W. C.
MacMillan, Science 2004, 305, 1752 – 1755; f) A. B. Northrup,
The synthesis of the ribose derivative 13 was carried out to
demonstrate the conversion of AROCM products such as 7
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I. K. Mangion, F. Hettche, D. W. C. MacMillan, Angew. Chem.
2004, 116, 2204 – 2206; Angew. Chem. Int. Ed. 2004, 43, 2152 –
2154; g) S. E. Denmark, W.-J. Chung, Angew. Chem. 2008, 120,
1916 – 1918; Angew. Chem. Int. Ed. 2008, 47, 1890 – 1892.
[4] a) J. K. Park, D. T. McQuade, Angew. Chem. 2012, 124, 2771 –
2775; Angew. Chem. Int. Ed. 2012, 51, 2717 – 2721; b) D. Kim,
J. S. Lee, S. B. Kong, H. Han, Angew. Chem. 2013, 125, 4297 –
4300; Angew. Chem. Int. Ed. 2013, 52, 4203 – 4206.
[5] a) E. El-Sayed, N. K. Anand, E. M. Carreira, Org. Lett. 2001, 3,
3017 – 3020; b) T. Luanphaisarnnont, C. O. Ndubaku, T. F.
Jamison, Org. Lett. 2005, 7, 2937 – 2940; c) S. B. Han, H. Han,
M. J. Krische, J. Am. Chem. Soc. 2010, 132, 1760 – 1761.
[6] Y. Zhao, J. Rodrigo, A. H. Hoveyda, M. L. Snapper, Nature
2006, 443, 67 – 70.
[15] W. Kirmse, F. Scheidt, H. J. Vater, J. Am. Chem. Soc. 1978, 100,
3945 – 3946.
[16] D. S. La, J. G. Ford, E. S. Sattely, P. J. Bonitatebus, R. R. Schrock,
A. H. Hoveyda, J. Am. Chem. Soc. 1999, 121, 11603 – 11604.
[17] Attempts to use cyclic protecting groups (ex: benzylidene acetal)
resulted in low conversion.
[18] In preliminary stoichiometric experiments with 1 and 5c, we
observe the formation of a kinetically stable intermediate
analogous to one described in a recent report on an enantiopure
ruthenium alkylidene complex: R. K. M. Khan, A. R. Zhugralin,
S. Torker, R. V. OꢁBrien, P. J. Lombardi, A. H. Hoveyda, J. Am.
Chem. Soc. 2012, 134, 12438 – 12441.
[19] a) R. M. Silverstein, R. G. Brownlee, T. E. Bellas, D. L. Wood,
L. E. Browne, Science 1968, 159, 889 – 891; b) T. Yasumoto, M.
Murata, Y. Oshima, M. Sano, G. K. Matsumoto, J. Clardy,
Tetrahedron 1985, 41, 1019 – 1025; c) D. Uemura, T. Chou, T.
Haino, A. Nagatsu, S. Fukuzawa, S. Z. Zheng, H. S. Chen, J. Am.
Chem. Soc. 1995, 117, 1155 – 1156; d) T. Chou, O. Kamo, D.
Uemura, Tetrahedron Lett. 1996, 37, 4023 – 4026; e) T. Chou, T.
Haino, M. Kuramoto, D. Uemura, Tetrahedron Lett. 1996, 37,
4027 – 4030.
[20] For previous syntheses, see: a) R. Bernardi, C. Fuganti, P.
Grasselli, Tetrahedron Lett. 1981, 22, 4021 – 4024; b) K. Mori,
Y. B. Seu, Tetrahedron 1985, 41, 3429 – 3431; c) F. Sato, O.
Takahashi, T. Kato, Y. Kobayashi, J. Chem. Soc. Chem.
Commun. 1985, 1638 – 1641; d) S. Hatakeyama, K. Sakurai, S.
Takano, J. Chem. Soc. Chem. Commun. 1985, 1759 – 1761; e) A.
Yusufoglu, S. Antons, H. D. Scharf, J. Org. Chem. 1986, 51,
3485 – 3487; f) J. Mulzer, A. Angermann, W. Munch, Liebigs
Ann. Chem. 1986, 825 – 838; g) A. C. Oehlschlager, B. D. John-
ston, J. Org. Chem. 1987, 52, 940 – 943; h) H. Redlich, W. Bruns,
W. Francke, V. Schurig, T. L. Payne, J. P. Vite, Tetrahedron 1987,
43, 2029 – 2034; i) J. M. Chong, E. K. Mar, Tetrahedron 1989, 45,
7709 – 7716; j) Y. Noda, M. Kikuchi, Chem. Lett. 1989, 1755 –
1756; k) S. Ramaswamy, A. C. Oehlschlager, J. Org. Chem. 1989,
54, 255 – 257; l) K. Matsumoto, N. Suzuki, H. Ohta, Tetrahedron
Lett. 1990, 31, 7163 – 7166; m) G. Pedrocchi-Fantoni, S. Servi, J.
Chem. Soc. Perkin Trans. 1 1991, 1764 – 1765; n) V. Cere, C.
Mazzini, C. Paolucci, S. Pollicino, A. Fava, J. Org. Chem. 1993,
58, 4567 – 4571; o) J. A. Soderquist, A. M. Rane, Tetrahedron
Lett. 1993, 34, 5031 – 5034; p) A. Gypser, M. Flasche, H. D.
Scharf, Liebigs Ann. Chem. 1994, 775 – 780; q) M. J. Kim, G. B.
Choi, J. Y. Kim, H. J. Kim, Tetrahedron Lett. 1995, 36, 6253 –
6256; r) S. Vettel, C. Lutz, P. Knochel, Synlett 1996, 731 – 733;
s) S. D. Burke, N. Muller, C. M. Beaudry, Org. Lett. 1999, 1,
1827 – 1829; t) J. K. Gallos, L. C. Kyradjoglou, T. V. Koftis,
Heterocycles 2001, 55, 781 – 784; u) S.-G. Kim, T.-H. Park, B. J.
Kim, Tetrahedron Lett. 2006, 47, 6369 – 6372; v) H.-Y. Lee, Y.
Jung, H. Moon, Bull. Korean Chem. Soc. 2009, 30, 771 – 772;
w) S. Singh, P. J. Guiry, J. Org. Chem. 2009, 74, 5758 – 5761.
[21] Attempts to utilize 4-penten-2-one resulted in recovered starting
material, which is likely due to deactivation of the catalyst by
formation of a stable chelating species.
[7] H. C. Brown, G. Narla, J. Org. Chem. 1995, 60, 4686 – 4687.
[8] A. H. Hoveyda, S. J. Malcolmson, S. J. Meek, A. R. Zhugralin,
Angew. Chem. 2010, 122, 38 – 49; Angew. Chem. Int. Ed. 2010, 49,
34 – 44.
[9] For a recent review, see: A. Fꢀrstner, Science 2013, 341, 1229713;
For leading references, see: a) K. Endo, R. H. Grubbs, J. Am.
Chem. Soc. 2011, 133, 8525 – 8527; b) B. K. Keitz, K. Endo, P. R.
Patel, M. B. Herbert, R. H. Grubbs, J. Am. Chem. Soc. 2012, 134,
693 – 699; c) L. E. Rosebrugh, M. B. Herbert, V. M. Marx, B. K.
Keitz, R. H. Grubbs, J. Am. Chem. Soc. 2013, 135, 1276 – 1279;
d) M. M. Flook, A. J. Jiang, R. R. Schrock, P. Mueller, A. H.
Hoveyda, J. Am. Chem. Soc. 2009, 131, 7962 – 7963; e) S. J.
Meek, R. V. OꢁBrien, J. Llaveria, R. R. Schrock, A. H. Hoveyda,
Nature 2011, 471, 461 – 466; f) R. K. M. Khan, S. Torker, A. H.
Hoveyda, J. Am. Chem. Soc. 2013, 135, 10258 – 10261.
[10] For a recent review, see: a) S. Kress, S. Blechert, Chem. Soc. Rev.
2012, 41, 4389 – 4408; for leading references, see b) J. M. Berlin,
S. D. Goldberg, R. H. Grubbs, Angew. Chem. 2006, 118, 7753 –
7757; Angew. Chem. Int. Ed. 2006, 45, 7591 – 7595; c) T. W. Funk,
J. M. Berlin, R. H. Grubbs, J. Am. Chem. Soc. 2006, 128, 1840 –
1846; d) J. Savoie, B. Stenne, S. K. Collins, Adv. Synth. Catal.
2009, 351, 1826 – 1832; e) B. Stenne, J. Timperio, J. Savoie, T.
Dudding, S. K. Collins, Org. Lett. 2010, 12, 2032 – 2035; f) S.
Tiede, A. Berger, D. Schlesiger, D. Rost, A. Luhl, S. Blechert,
Angew. Chem. 2010, 122, 4064 – 4067; Angew. Chem. Int. Ed.
2010, 49, 3972 – 3975; g) A. Kannenberg, D. Rost, S. Eibauer, S.
Tiede, S. Blechert, Angew. Chem. 2011, 123, 3357 – 3360; Angew.
Chem. Int. Ed. 2011, 50, 3299 – 3302; h) R. K. M. Khan, R. V.
OꢁBrien, S. Torker, B. Li, A. H. Hoveyda, J. Am. Chem. Soc.
2012, 134, 12774 – 12779; i) M. Yu, I. Ibrahem, M. Hasegawa,
R. R. Schrock, A. H. Hoveyda, J. Am. Chem. Soc. 2012, 134,
2788 – 2799.
[11] a) M. L. Randall, J. A. Tallarico, M. L. Snapper, J. Am. Chem.
Soc. 1995, 117, 9610 – 9611; b) M. L. Snapper, J. A. Tallarico,
M. L. Randall, J. Am. Chem. Soc. 1997, 119, 1478 – 1479; c) J. A.
Tallarico, M. L. Randall, M. L. Snapper, Tetrahedron 1997, 53,
16511 – 16520; d) T. O. Schrader, M. L. Snapper, J. Am. Chem.
Soc. 2002, 124, 10998 – 11000; e) B. H. White, M. L. Snapper, J.
Am. Chem. Soc. 2003, 125, 14901 – 14904.
[12] J. Hartung, R. H. Grubbs, J. Am. Chem. Soc. 2013, 135, 10183 –
10185.
[22] The absolute configurations of the AROCM products in this
study were assigned by analogy to 11 and 13.
[13] P. E. Howse, I. D. R. Stevens, Insect Pheromones and their Use in
Pest Management, Chapman & Hall, New York, 1998.
[14] Recent work from this group has demonstrated the application
of racemic 1 to the synthesis of Lepidoptera female sex
pheromones: M. B. Herbert, V. M. Marx, R. L. Pederson, R. H.
Grubbs, Angew. Chem. 2013, 125, 328 – 332; Angew. Chem. Int.
Ed. 2013, 52, 310 – 314.
[23] a) J. K. Cha, W. J. Christ, Y. Kishi, Tetrahedron Lett. 1983, 24,
3943 – 3946; b) W. J. Christ, J. K. Cha, Y. Kishi, Tetrahedron Lett.
1983, 24, 3947 – 3950.
[24] a) R. R. Schmidt, A. Gohl, Chem. Ber. 1979, 112, 1689 – 1704;
b) P. A. Wender, F. C. Bi, N. Buschmann, F. Gosselin, C. Kan, J.-
M. Kee, H. Ohmura, Org. Lett. 2006, 8, 5373 – 5376.
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