Nickel-catalyzed allylation of allyl carbonates with homoallyl alcohols via retro-allylation providing 1,5-hexadienes

Article abstract of DOI:10.1021/ol800335v

A highly efficient and mild method for the synthesis of 1,5-hexadienes, nickel-catalyzed reactions of Boc-protected allyl alcohols with homoallyl alcohols, has been developed. Nickel-mediated retro-allylation allows for the use of homoallyl alcohols as allylmetal equivalents in the synthesis of 1,5-hexadienes.2008 American Chemical Society.

Full text of DOI:10.1021/ol800335v

ORGANIC
LETTERS
2008
Vol. 10, No. 8
1629-1632
Nickel-Catalyzed Allylation of Allyl
Carbonates with Homoallyl Alcohols via
Retro-Allylation Providing
1,5-Hexadienes
Yuto Sumida, Sayuri Hayashi, Koji Hirano, Hideki Yorimitsu,* and
Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto UniVersity,
Kyoto-daigaku Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
yori@orgrxn.mbox.media.kyoto-u.ac.jp; oshima@orgrxn.mbox.media.kyoto-u.ac.jp
Received February 14, 2008
ABSTRACT
A highly efficient and mild method for the synthesis of 1,5-hexadienes, nickel-catalyzed reactions of Boc-protected allyl alcohols with homoallyl
alcohols, has been developed. Nickel-mediated retro-allylation allows for the use of homoallyl alcohols as allylmetal equivalents in the synthesis
of 1,5-hexadienes.
Palladium-catalyzed cross-coupling reactions of allyl elec-
trophiles with allylmetals are potentially useful for the
synthesis of 1,5-hexadienes.1-5 Despite its seeming simplic-
ity, the reactions usually suffer from low yields because of
â-hydride elimination from (substituted-allyl)palladium in-
termediates such as crotylpalladium6 and concomitant forma-
tion of undesired homocoupling products.7 In most cases,
allylstannanes were used as the allylmetal, which required a
troublesome purification procedure.3 Thus, efficient methods
for the synthesis of 1,5-hexadienes from allylmetals and allyl
electrophiles are rare and should be developed.
We have recently developed palladium-catalyzed allylation
reactions of aryl halides with homoallyl alcohols as allylmetal
equivalents by taking advantage of palladium-mediated retro-
allylation.8,9 Pursuing a new efficient method for the synthesis
of 1,5-hexadienes, we attempted to apply the retro-allylation-
based methodology to the palladium-catalyzed reaction of
(1) Reviews: Negishi, E.; Liao, B. In Handbook of Organopalladium
Chemistry for Organic Synthesis; Negishi, E., Ed.; Wiley: New York, 2002;
Vol. 1, Chapter III.2.10.
(2) Pioneering work: (a) Trost, B. M.; Keinan, E. Tetrahedron Lett. 1980,
21, 2595-2598. (b) Godschalx, J.; Stille, J. K. Tetrahedron Lett. 1980, 21,
2599-2602.
(6) Keinan, E.; Kumar, S.; Dangur, V.; Vaya, J. J. Am. Chem. Soc. 1994,
116, 11151-1152.
(3) With allylstannanes: (a) Yoshida, J.; Funahashi, H.; Iwasaki, H.;
Kawabata, N. Tetrahedron Lett. 1986, 27, 4469-4472. (b) Farina, V.; Baker,
S. R.; Benigni, D. A.; Sapino, C. Tetrahedron Lett. 1988, 29, 5739-5742.
(c) Yamamoto, Y.; Hatsuya, S.; Yamada, J. J. Org. Chem. 1990, 55, 3118-
3128. Intramolecular versions: (d) Cuerva, J. M.; Go´mez-Bengoa, E.;
Me´ndez, M.; Echavarren, A. M. J. Org. Chem. 1997, 62, 7540-7541. (e)
Me´ndez, M.; Cuerva, J. M.; Go´mez-Bengoa, E.; Ca´rdenas, D. J.; Echavarren,
A. M. Chem. Eur. J. 2002, 8, 3620-3628.
(4) With allylsilanes: (a) Hatanaka, Y.; Hiyama, T. J. Org. Chem. 1988,
53, 918-920. (b) Hatanaka, Y.; Ebina, Y.; Hiyama, T. J. Am. Chem. Soc.
1991, 113, 7075-7076. (c) Terakado, M.; Miyazawa, M.; Yamamoto, K.
Synlett 1994, 134-136. (d) Reference 3e.
(5) With allylindiums: Lee, P. H.; Sung, S.; Lee, K.; Chang, S. Synlett
2002, 146-148.
(7) Goliaszewski, A.; Schwartz, J. Organometallics 1985, 4, 417-419.
(8) (a) Hayashi, S.; Hirano, K.; Yorimitsu, H.; Oshima, K. J. Am. Chem.
Soc. 2006, 128, 2210-2211. (b) Iwasaki, M.; Hayashi, S.; Hirano, K.;
Yorimitsu, H.; Oshima, K. J. Am. Chem. Soc. 2007, 129, 4463-4469. (c)
Iwasaki, M.; Hayashi, S.; Hirano, K.; Yorimitsu, H.; Oshima, K. Tetrahedron
2007, 63, 5200-5203. (d) Hayashi, S.; Hirano, K.; Yorimitsu, H.; Oshima,
K. J. Am. Chem. Soc. 2007, 129, 12650-12651. (e) Ohmura, T.; Awano,
T.; Suginome, M.; Yorimitsu, H.; Oshima, K. Synlett 2008, 423-427.
(9) Reviews for carbon-carbon bond cleavage of tertiary alcohols: (a)
Muzart, J. Tetrahedron 2005, 61, 9423-9463. (b) Nishimura, T.; Uemura,
S. Synlett 2004, 201-216. (c) Kondo, T.; Mitsudo, T. Chem. Lett. 2005,
34, 1462-1467. (d) Murakami, M.; Makino, M.; Ashida, S.; Matsuda, T.
Bull. Chem. Soc. Jpn. 2006, 79, 1315-1321. (e) Satoh, T.; Miura, M. Top.
Organomet. Chem. 2005, 14, 1-20.
10.1021/ol800335v CCC: $40.75
© 2008 American Chemical Society
Published on Web 03/21/2008

cinnamyl acetate (1) with homoallyl alcohol (2a) (Scheme
1). However, the reaction was unsatisfactory, highlighting
Table 1. Nickel-Catalyzed Allylation of Boc-Protected
Cinnamyl Alcohols 7 with Branched Homoallyl Alcohols 2
Scheme 1. Palladium-Catalyzed Allylation of Cinnamyl
Acetate (1) with Homoallyl Alcohol 2aa
entry
R1
7
R2
R3
2
3
yield % B/L
1
2
3
4
5
6
7
Ph
7a Me
iPr 2a 3a
iPr 2a 3b
iPr 2a 3c
iPr 2a 3d
91
70
78
86
60
77
79
37:63
40:60
33:67
37:63
26:74
9:91
4-MeOC6H4 7b Me
4-CF3C6H4 7c Me
2-MeC6H4
Ph
Ph
Ph
7d Me
7a nC7H15 Me 2b 3e
7a cC6H11 Me 2c 3f
7a tBu
Me 2d 3g
3:97
2-4). Replacement of the methyl group in 2a (R2 ) Me)
with a heptyl group (R2 ) nC7H15) slightly improved the
regioselectivity (entry 5). Cyclohexyl-substituted homoallyl
alcohol 2c reacted with 7a to yield the corresponding 1,5-
hexadiene in a higher branched/linear ratio of 9:91 (entry
6). The highest branched/linear ratio was observed in the
reaction of 7a with t-butyl-substituted homoallyl alcohol 2d
(3:97, entry 7).
It is worth noting that the reaction of Boc-protected crotyl
alcohol 7e with phenyl-substituted alcohol 2e (eq 1) yielded
3a in the same branched/linear ratio as is shown in entry 1
of Table 1. The same branched/linear ratio strongly suggests
that the reactions proceed via the same diallylnickel inter-
mediate. Based on this fact, a plausible mechanism is
proposed in Scheme 2. Oxidative addition of 7 to a nickel
catalyst followed by decarboxylation would afford alkoxy-
aThe italicized Pd means that the palladium has either no, one,
or two phosphine ligands.
the difficulty in achieving efficient synthesis of 1,5-hexa-
dienes: branched-coupling product 3a-B was obtained in
only 25% yield, and â-methylstyrene was mainly formed.
The formation of â-methylstyrene would result from pre-
dominant â-hydride elimination from intermediate 6′ or other
isomers6 over productive reductive elimination from 6. Many
attempts to find suitable reaction conditions for the pal-
ladium-catalyzed allylation reaction of 1 with 2a failed.
We then turned our attention to nickel catalysis, although
little is known about the nickel-catalyzed cross-coupling
reaction of allylmetals with allyl electrophiles10 and no
information about nickel-mediated retro-allylation was re-
ported. After screening reaction conditions, we found that a
combination of 5 mol % of Ni(cod)2 (cod ) 1,5-cycloocta-
diene) and 10 mol % of triethyl phosphite catalyzed the
allylation reaction of Boc-protected cinnamyl alcohol 7a (Boc
) t-butoxycarbonyl) with 2a in the absence of base in
refluxing toluene (Table 1, entry 1).11 The reaction afforded
the corresponding coupling products 3a-B and 3a-L in high
yield in a ratio of 3a-B/3a-L ) 37:63. Unfortunately, the
ligand effect on the isomer ratio was almost negligible as
far as we examined.
Scheme 2. Plausible Reaction Mechanisma
Electronic as well as steric factors of the aryl groups of 7
had little influence on this allylation reaction (Table 1, entries
(10) Stoichiometric reactions of π-allylnickels with electrophiles includ-
ing allylic ones were well documented: (a) Billington, D. C. Chem. Soc.
ReV. 1985, 14, 93-120. (b) Billington, D. C. In ComprehensiVe Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol.
3, Chapter 2.1.
(11) Typical Procedure: Ni(cod)2 (3.4 mg, 0.0125 mmol) was placed
in a 20 mL reaction flask. Toluene (1.0 mL) and P(OEt)3 (4 mL, 0.025
mmol) were added, and the resulting suspension was stirred for 10 min at
room temperature. Carbonate 7a (59 mg, 0.25 mmol) and homoallyl alcohol
2a (51 mg, 0.30 mmol) were then added, and the mixture was heated at
reflux for 5 h. The reaction was then quenched with water (2 mL). Extraction
followed by purification on silica gel provided a mixture of (E)-1-phenyl-
1,5-heptadiene (3a-L) and 4-methyl-1-phenyl-1,5-hexadiene (3a-B) in
91% combined yield (39 mg, 0.23 mmol, B/L ) 37:63).
a The italicized Ni means that the nickel has either no, one, or
two phosphite ligands.
1630
Org. Lett., Vol. 10, No. 8, 2008

(π-allyl)nickel intermediate 9. Ligand exchange with 2 would
yield 10. Retro-allylation12 would then take place to afford
although a higher temperature was necessary to attain high
yields in some cases (entries 10, 11, and 15).
11 with concomitant formation of ketone R3 CdO. Here the
The reactions of 7a with aryl-substituted homoallyl alco-
hols 14 afforded the corresponding cross-coupling products
1,6-diaryl-1,5-hexadienes 15 exclusively in excellent yields
(Scheme 3). None of the homocoupling products were
observed in the reactions that yielded 15b and 15c.
2
configurations and modes of coordination of the allyl ligands
R1CHCHCH2 and R2CHCHCH2 would be completely
scrambled to yield a mixture of several diallylnickel inter-
mediates such as 11, 11′, and 11′′. Reductive elimination
prior to â-hydride elimination would afford product 3 and
regenerate the initial zerovalent nickel catalyst.
Scheme 3. Synthesis of 1,6-Diaryl-1,5-hexadienes (14a ) 2e)
Methallylation of various Boc-protected allyl alcohols 7
proceeded smoothly by using 12a (Table 2, entries 1-8).
The nickel-catalyzed reactions of 7a with silyl-substituted
homoallyl alcohols 16 yielded the corresponding linear cross-
coupling products 17-L in high yields (Scheme 4). Interest-
Table 2. Nickel-Catalyzed Allylation of Boc-Protected
Cinnamyl Alcohols 7 with Homoallyl Alcohols 12a and 12b
Scheme 4. Selective Preparation of Vinylsilanes and
Allylsilanes under Nickel and Palladium Catalysis
entry
R1
7
12
13
yield %
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Ph
7a
7b
7c
7d
7f
7g
7h
7i
7a
7b
7c
7d
7f
12a
12a
12a
12a
12a
12a
12a
12a
12b
12b
12b
12b
12b
12b
12b
13a
13b
13c
13d
13e
13f
13g
13h
13i
13j
13k
13l
13m
13n
13o
99
71
94
84
100
76
76
82
96
81a
80a
84
88
62
89a
4-MeOC6H4
4-CF3C6H4
2-MeC6H4
4-MeC6H4
2-furyl
2-thienyl
MePh2Si
Ph
4-MeOC6H4
4-CF3C6H4
2-MeC6H4
4-MeC6H4
2-thienyl
MePh2Si
ingly, the sense of the regioselectivity was opposite when a
palladium catalyst was used. The palladium-catalyzed reac-
tions of 1 with 16 afforded branched allylsilanes 17-B
exclusively.
7h
7i
The reason for the different regiochemical outcomes is
not clear at this stage. The mode of reductive elimination
a Xylene was used instead of toluene.
Scheme 5. Plausible Transition States for Reductive
Elimination
Furyl- and thienyl-substituted 7g and 7h also participated in
the reaction. Interestingly, the reaction of 7i having a
methyldiphenylsilyl group with 12a afforded 5-methyl-1,5-
hexadienylsilane 13h as the sole product in high yield.
Allylation with 12b also proceeded smoothly (entries 9-15),
(12) Another plausible path yielding 11 or other isomers is â-carbon
elimination from 10. However, ab initio calculations revealed that retro-
allylation is a far more favorable process than â-carbon elimination in the
case of ruthenium: Sakaki, S.; Ohki, T.; Takayama, T.; Sugimoto, M.;
Kondo, T.; Mitsudo, T. Organometallics 2001, 20, 3145-3158.
Org. Lett., Vol. 10, No. 8, 2008
1631

from diallylnickel species would be different from that of
diallylpalladium (Scheme 5). In the case of nickel, the
carbon-carbon formation would take place between the less
substituted carbons of the allyl moieties on the nickel via a
transition state 18 or 19. In contrast, the carbon-carbon
formation from diallylpalladium would take place with allylic
rearrangement via a transition state 20 or 21.3e
In summary, we have developed an efficient method for
the synthesis of 1,5-hexadienes, nickel-catalyzed reactions
of Boc-protected allyl alcohols with homoallyl alcohols.
Nickel-mediated retro-allylation allows for the use of homo-
allyl alcohols as allylmetal equivalents in the synthesis of
1,5-hexadienes.
Acknowledgment. This work was supported by Grants-
in-Aid for Scientific Research from MEXT and JSPS. S.H.
and K.H. acknowledge JSPS for financial support.
Supporting Information Available: Characterization
data of the products. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL800335V
1632
Org. Lett., Vol. 10, No. 8, 2008