Efficient and stereoselective synthesis of yellow scale pheromone via alkyne haloboration, Zr-catalyzed asymmetric carboalumination of alkenes (ZACA reaction), and Pd-catalyzed tandem negishi coupling

Article abstract of DOI:10.1021/ol8017566

(Chemical Equation Presented) A Pd-catalyzed reaction of allylzincs with the 1-octyne bromoboration product gives the desired allyl-alkenyl coupling products in good yields except with H₂C=CHCH₂ZnBr. This reaction is suitable for con

Full text of DOI:10.1021/ol8017566

ORGANIC
LETTERS
2008
Vol. 10, No. 19
4311-4314
Efficient and Stereoselective Synthesis
of Yellow Scale Pheromone via Alkyne
Haloboration, Zr-Catalyzed Asymmetric
Carboalumination of Alkenes (ZACA
Reaction), and Pd-Catalyzed Tandem
Negishi Coupling
Zhaoqing Xu and Ei-ichi Negishi*
Herbert C. Brown Laboratories of Chemistry, Purdue UniVersity, 560 OVal DriVe,
West Lafayette, Indiana 47907-2084
negishi@purdue.edu
Received July 30, 2008
ABSTRACT
A Pd-catalyzed reaction of allylzincs with the 1-octyne bromoboration product gives the desired allyl-alkenyl coupling products in good
yields except with H2CdCHCH2ZnBr. This reaction is suitable for converting an alkyne bromoboration product 3 into 4 with no isomerization
or ꢀ-elimination. The Pd-catalyzed isoalkyl-alkenyl coupling of 4 with the isoalkylzinc reagent derived from 2 provides yellow scale pheromone
(1) of g98% isomeric purity in 34% in six steps from TBDPS-protected homoallyl alcohol.
Hydrometalation and carbometalation of alkynes followed
by Pd-catalyzed cross-coupling1 have provided a variety of
highly stereoselective and efficient routes to di- and trisub-
stituted alkenes.2 Even so, however, there still are a large
number of trisubstituted alkenes that are not readily prepa-
rable by these methods, as exemplified by the sex pheromone
of yellow scale (1),3 a pest of citrus and ornamental plants.
It was isolated and identified without the establishment of
full stereochemical details by Gieselmann and his co-workers
(2) For recent reviews, see: (a) Negishi, E., Ed. Handbook of
Organopalladium Chemistry for Organic Synthesis; Wiley-Interscience: New
York, 2002; p 3279; Chapters III.2.6, III.2.9, III.2.11, III.2.15. (b) de Meijere,
A., Diederich, F., Eds. Metal-catalyzed Cross-Coupling Reactions; Wiley-
VCH: Weinheim, 2004; 916 pp. (c) Negishi, E.; Hu, Q.; Huang, Z.; Qian,
M.; Wang, G. Aldrichim. Acta 2005, 38, 71–88. (d) Negishi, E.; Huang,
Z.; Wang, G.; Mohan, S.; Wang, C.; Hattori, H. Acc. Chem. Res., in
press.
(3) (a) Gieselmann, M. J.; Moreno, D. S.; Fargerleund, J.; Tashiro, H.;
Roelofs, W. L. J. Chem. Ecol. 1979, 5, 25–31. (b) Anderson, R. J.; Henrick,
C. A. J. Chem. Ecol. 1979, 5, 773–779. (c) Suguro, T.; Roelofs, W. L.;
Mori, K. Agric. Biol. Chem. 1981, 45, 2509–2514. (d) Masuda, S.;
Kuwahara, S.; Suguro, T.; Mori, K. Agric. Biol. Chem. 1981, 45, 2515–
2520. (e) Mori, K.; Kuwahara, S. Tetrahedron 1982, 38, 521–525. (f) Millar,
J. G. Tetrahedron Lett. 1989, 30, 4913–4914.
(1) For seminal contributions, see: (a) Negishi, E.; Baba, S. J. Chem.
Soc., Chem. Commun. 1976, 596, 597. (b) Baba, S.; Negishi, E. J. Am.
Chem. Soc. 1976, 98, 6729–6731. (c) Negishi, E.; Van Horn, D. E. J. Am.
Chem. Soc. 1977, 99, 3168–3170. (d) Okukado, N.; Van Horn, D. E.; Klima,
W. L.; Negishi, E. Tetrahedron Lett. 1978, 1027, 1030. (e) Negishi, E.;
Okukado, N.; King, A. O.; Van Horn, D. E.; Spiegel, B. I. J. Am. Chem.
Soc. 1978, 100, 2254–2256. (f) Miyaura, N.; Yamada, K.; Suzuki, A.
Tetrahetron Lett. 1979, 3437, 3440.
10.1021/ol8017566 CCC: $40.75
Published on Web 09/03/2008
2008 American Chemical Society

Scheme 1. Regio- and Stereoselective Synthesis of Yellow Scale Pheromone
in 1979.3a In the same year, the active isomer of 1 was shown
to be the 5E isomer by a deliberate synthesis of a mixture
of the 5E and 5Z isomers by Anderson and Henrick.3b Mori
and his co-workers subsequently established the 3S config-
uration of the active isomer through asymmetric syntheses
of both enantiomers.3d,e Although highly stereoselective, their
syntheses based on the chiral pool protocol suffered from a
lengthy sequence of over 10 steps from methyl (R)-(+)-
citronellate in 7-10% overall yields. A very promising,
convergent, but nonasymmetric route to 1 via silylcupration4
was devised more recently by Millar.3f
The synthetically challenging trisubstituted alkene moiety
of 1 and an opportunity for applying the ZACA reaction (Zr-
catalyzed asymmetric carboalumination of alkenes),5 espe-
cially one-pot synthesis of (2S)-4-tert-butyldiphenylsilyloxy-
2-methyl-1-butanol (2) of 98% ee in 52% yield from TBDPS-
protected 3-buten-1-ol,5d prompted us to devise an efficient
and regio- and stereoselective synthesis of 1, as outlined in
Scheme 1.
For construction of the trisubstituted alkene moiety, applica-
tion of alkyne haloboration developed by Suzuki7 was consid-
ered, and stereoselective formation of 3 in ca. 80% yield by
the reaction of 3-methyl-1-butyne with BBr3 in CH2Cl2 was
observed. This was to be followed by selective and high-yielding
cross-coupling. The high propensity of the bromoboration
products, such as 3, to undergo unwanted dehaloboration
together with the modest reactivity of hindered alkenyl bromide
would make desired C-C bond formation via cross-coupling
of 3 challenging. In fact, the only known satisfactory cross-
coupling appeared to be the Pd-catalyzed organozinc reaction2
employed by Suzuki.7 It then occurred to us that, whereas the
Pd-catalyzed alkenylmetal-allyl electrophile (alkenyl-allyl,
hereafter) coupling had been extensively investigated, generally
high-yielding, and often highly regio- and stereospecific with
retention with respect to both alkenyl and allyl groups,8 little
had been known about the corresponding allylmetal-alkenyl
electrophile (allyl-alkenyl, hereafter) coupling.8b Since the Pd-
catalyzed alkenyl-allyl coupling was not a viable option for
the task at hand, however, the Pd-catalyzed allyl-alkenyl
coupling of (Z)-(2-bromo-1-octenyl)dibromoborane, generated
by treating 1-octyne with BBr3 in CH2Cl2, with allylzinc
bromide and its variously carbon-substituted derivatives gener-
ated by treating the corresponding allylic bromides with Zn dust
was examined.9 The results summarized in Table 1 indicate
the following: (1) The Pd-catalyzed allyl-alkenyl coupling with
the parent allylzinc bromide does not occur under the conditions
used, but all of the other cases including those involving
2-methylallylzinc bromide gave the desired products in good
yields. The sterically least demanding parent allylzinc bromide
may act as a catalyst poison, although this point needs to be
further investigated. (2) As anticipated, the Pd-catalyzed
allyl-alkenyl coupling is more readily prone to stereoisomer-
ization. Thus, the allylic organozinc reagents derived from both
geranyl and neryl bromides led to the formation of essentially
identical mixtures of the 4E and 4Z isomers (E/Z ) 2.5/1)
without producing detectable amounts of regioisomers. These
results are in sharp contrast with the corresponding Pd-catalyzed
alkenyl-allyl coupling proceeding with essentially complete
retention of both stereo- and regiochemical identities.8 Despite
these limitations, the desired case of the conversion of 3 to 4
via Pd-catalyzed cross-coupling of 3 with 3-methyl-2-butenylz-
inc bromide in the presence of 1 mol % of Pd(PPh3)2Cl2
followed by iodinolysis with I2 (2 equiv) and NaOAc (1.5 equiv)
proceeded cleanly with no detectable sign of isomerization to
give 4 (g98% E) in 77% yield from 3-methyl-1-butyne.
(4) For a seminal paper on silylcupration, see: Fleming, I.; Newton,
T. W.; Roessler, F. J. Chem. Soc., Perkin Trans. 1 1981, 252, 7–2532.
(5) For seminal and pertinent papers on the ZACA reaction, see: (a)
Kondakov, D.; Negishi, E. J. Am. Chem. Soc. 1995, 117, 10771–10772.
(b) Kondakov, D.; Negishi, E. J. Am. Chem. Soc. 1996, 118, 1577–1578.
(c) Huo, S.; Shi, J.; Negishi, E. Angew. Chem., Int. Ed. 2002, 41, 2141–
2143. (d) Huang, Z.; Tan, Z.; Novak, T.; Zhu, G.; Negishi, E. AdV. Synth.
Catal. 2007, 349, 539–545.
(6) Erker, G.; Aulbach, M.; Knickmeier, M.; Wingbermuhle, D.; Kruger,
C.; Nolte, M.; Werner, S. J. Am. Chem. Soc. 1993, 115, 4590.
(7) (a) Satoh, Y.; Serizawa, H.; Miyaura, N.; Hara, S.; Suzuzki, A.
Tetrahedron Lett. 1988, 29, 1811–1814. (b) For a seminal report on alkyne
haloboration, see: Lappert, M. F.; Prokai, B. J. Organomet. Chem. 1964,
1, 384–400.
(8) (a) Matsushita, H.; Negishi, E. J. Am. Chem. Soc. 1981, 103, 2882–
2884. (b) For a review, see: Negishi, E.; Liu, F. Chapter III.2.9 in
ref 2a.
(9) (a) Shriner, R. L.; Neumann, F. W. Organic Synthesis; Wiley: New
York, 1955; Vol. III, p 73. (b) Negishi, E.; Matsushita, H.; Okukado, N.
Tetrahedron Lett. 1981, 22, 2715–2718.
4312
Org. Lett., Vol. 10, No. 19, 2008

Table 1. Scope of a Tandem Process Consisting of Alkyne Haloboration-Pd-Catalyzed Negishi Coupling with Allylzinc Bromidea
a All reactions were run with 1.0 equiv of BBr3, 1.2 equiv of allylzinc bromide generated by treating the corresponding allylic bromides with Zn dust,
c
2.0 equiv of I2, and 1.5 equiv of NaOAc. b All yields refer to isolated yields. No allyl-alkenyl coupling product was observable by GC and H NMR.
1
For the final assembly of the full carbon skeleton of the
yellow scale pheromone (1), 2 was iodinated in 97% yield
by its treatment with I2 (1.2 equiv), PPh3 (1.15 equiv), and
imidazole (1.3 equiv) in CH2Cl2. The iodide thus obtained
was treated with t-BuLi (2.2 equiv) in ether10 followed by
zincation with dry ZnBr2. The Pd-catalyzed isoalkyl-alkenyl
coupling of the in situ generated isoalkylzinc reagent with 4
in the presence of 1 mol % of Pd(PPh3)4 followed by
desilylation with TBAF (1.2 equiv), provided 5 as a g98%
pure compound in 74% yield from the two iodide precur-
sors,11 and its acetylation gave the desired yellow scale
pheromone (1) of g98% isomeric purity in 92% yield. Thus,
1 was synthesized in 34% yield over six steps in the longest
linear sequence from TBDPS-protected 3-buten-1-ol or in
54% yield over four steps from 3-methyl-1-butyne.
give the desired allyl-alkenyl coupling products under the
conditions used. Fortunately, all of the other allylzinc
derivatives with one or two substituents in the C2 or C3
positionhavesmoothlyreactedtogivethedesiredallyl-alkenyl
coupling products in good yields. As anticipated, however,
this allyl-alkenyl coupling has proven to be more readily
prone to regio- and/or stereoscrambling than the previously
developed alkenyl-allyl coupling.8 (2) The Pd-catalyzed
allyl-alkenyl coupling proved to be exactly what was needed
for converting the alkyne bromoboration product 3 into one
of the key intermediates 4 for the synthesis of yellow scale
pheromone (1), which proceeded in 77% yield without being
accompanied by any isomerization or unwanted debromobo-
ration of 3 to detectable extents. (3) The other key intermedi-
ate 2 was prepared in 52% yield as a 99% pure R isomer
via the ZACA reaction of t-BuPh2Si-protected homoallyl
alcohol followed by enantiomeric purification by Amano PS
lipase-catalyzed acetylation of the unwanted S isomer. (4)
Iodination of 2 in 97% yield was followed by its in situ
lithiation-zincation and Pd-catalyzed cross-coupling of the
isoalkylzinc reagent thus generated with the alkenyl iodide
4 cleanly produced isomerically pure (g98%) 5 in 74% yield
from the two iodide precursors. Acetylation of 5 produced
the sex pheromone of yellow scale (1) of g98% isomeric
purity even before purification in 34% yield from t-BuPh2Si-
In summary, the following notable findings have been
discovered in this work. (1) The hitherto essentially unex-
plored Pd-catalyzed allylzinc-alkenyl electrophile coupling
has been investigated. The parent allylzinc bromide does not
(10) (a) Negishi, E.; Swanson, D. R.; Rousset, C. J. J. Org. Chem. 1990,
55, 5406–5409. (b) Bailey, W. F.; Punzalan, E. R. J. Org. Chem. 1990, 55,
5404–5406.
(11) For conceptually related applications of tandem Negishi coupling
processes to the synthesis of allenenynes and enediynes, see: (a) Wang,
K. K.; Wang, Z. Tetrahedron Lett. 1994, 35, 1829–1832. (b) Wang, K. K.;
Wang, Z.; Tarli, A.; Gannett, P. J. Am. Chem. Soc. 1996, 118, 10783–
10791. (c) Tarli, A.; Wang, K. K. J. Org. Chem. 1997, 62, 8841–8847.
Org. Lett., Vol. 10, No. 19, 2008
4313

protected homoallyl alcohol in six steps or in 54% yield from
3-methyl-l-butyne in four steps.
The results presented herein provide yet another example
demonstrating the synthetic utility of the ZACA-Pd-
catalyzed cross-coupling synergy,12 which, in this case, is
further promoted by alkyne haloboration.
Acknowledgment. We thank the National Institutes of
Health (GM 36792) and Purdue University for support of
this research. We also thank Albemarle, Wako Chemical Co.,
and NICHIA Corp. for their support and Dr. Z. Huang of
our laboratories for technical assistance.
Supporting Information Available: Experimental
(12) (a) Negishi, E.; Tan, Z.; Liang, B.; Novak, T. Proc. Nat. Acad.
Sci. U.S.A. 2004, 101, 5782–5787. (b) Tan, Z.; Negishi, E. Angew. Chem.,
Int. Ed. 2004, 43, 2911–2914. (c) Magnin-Lachaux, M.; Tan, Z.; Liang,
B.; Negishi, E. Org. Lett. 2004, 6, 1425–1427. (d) Novak, T.; Tan, Z.; Liang,
B.; Negishi, E. J. Am. Chem. Soc. 2005, 127, 2838–2839. (e) Liang, B.;
Novak, T.; Tan, Z.; Negishi, E. J. Am. Chem. Soc. 2006, 128, 2770–2771.
(f) Zhu, G.; Negishi, E. Org. Lett. 2007, 9, 2771–2774. (g) Zhu, G.; Liang,
B; Negishi, E. Org. Lett. 2008, 10, 1099–1101.
1
details and representative H and 13C NMR spectra. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL8017566
4314
Org. Lett., Vol. 10, No. 19, 2008