Rhodium-catalyzed allyl transfer from homoallyl alcohols to aldehydes via retro-allylation followed by isomerization into ketones

Article abstract of DOI:10.1021/ol060710v

Retro-allylation of homoallyl alcohol by rhodium catalysis occurs to generate allylrhodium species. This allylrhodium reacts with aldehydes to give the corresponding secondary alcohols in situ. Isomerization of these alcohols proceeds in the same pots to furnish the corresponding saturated ketones in good yields.

Full text of DOI:10.1021/ol060710v

ORGANIC
LETTERS
2006
Vol. 8, No. 12
2515-2517
Rhodium-Catalyzed Allyl Transfer from
Homoallyl Alcohols to Aldehydes via
Retro-Allylation Followed by
Isomerization into Ketones
Yuko Takada, 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 March 23, 2006
ABSTRACT
Retro-allylation of homoallyl alcohol by rhodium catalysis occurs to generate allylrhodium species. This allylrhodium reacts with aldehydes
to give the corresponding secondary alcohols in situ. Isomerization of these alcohols proceeds in the same pots to furnish the corresponding
saturated ketones in good yields.
Allylation of carbonyl compounds is among the most
important reactions in organic synthesis.1 Although many
allylmetal reagents are used for the allylation, rhodium-
mediated carbonyl allylation is quite rare.2,3
Recently, we have developed the metal-mediated retro-
allylation of homoallyl alcohols as a carbon-carbon bond-
cleavage strategy and succeeded in the generation and use
of regio- and stereochemically defined allylmetals.4 In the
course of this study, we found that this system could be
applied to rhodium catalysis. Herein, we wish to report a
new method for the generation of allylrhodium reagents from
homoallyl alcohols via retro-allylation5 and their reaction
with carbonyl compounds involving allylation.
Treatment of benzaldehyde (1a, 0.5 mmol) with homoallyl
alcohol 2a (1.0 mmol) in the presence of 2.5 mol % of [RhCl-
(cod)]2, 10 mol % of P(tBu)3, and 15 mol % of cesium
carbonate in refluxing xylene (5.0 mL) for 24 h provided
3-methyl-1-phenyl-1-butanone (3a) in 83% yield (Scheme
1). Retro-allylation of homoallyl alcohol by rhodium catalysis
would occur to generate σ-methallylrhodium,6 which is in
equilibrium with π-methallylrhodium. Methallylation of 1a
followed by isomerization of the corresponding secondary
alcohol would furnish the product (vide infra). This is the
first example of transition-metal-catalyzed allyl transfer to
carbonyl compounds via retro-allylation.7
(1) (a) Yamamoto, Y.; Asao, N. Chem. ReV. 1993, 93, 2207-2293. (b)
Denmark, S. E.; Fu, J. Chem. ReV. 2003, 103, 2763-2793.
(2) (a) Shi, M.; Lei, G.-X.; Masaki, Y. Tetrahedron: Asymmetry 1999,
10, 2071-2074. (b) Masuyama, Y.; Kaneko, Y.; Kurusu, Y. Tetrahedron
Lett. 2004, 45, 8969-8971.
(3) Rhodium-catalyzed allylic alkylations: (a) Tsuji, J.; Minami, I.;
Shimidzu, I. Tetrahedron Lett. 1984, 25, 5157-5160. (b) Hayashi, T.;
Okada, A.; Suzuka, T.; Kawatsura, M. Org. Lett. 2003, 5, 1713-1715. (c)
Evans, P. A.; Uraguchi, D. J. Am. Chem. Soc. 2003, 125, 7158-7159. (d)
Ashfeld, B. L.; Miller, K. A.; Martin, S. F. Org. Lett. 2004, 6, 1321-1324.
(e) Yasui, N.; Mizutani, K.; Yorimitsu, H.; Oshima, K. Tetrahedron 2006,
62, 1410-1415.
(4) (a) Fujita, K.; Yorimitsu, H.; Oshima, K. Chem. Rec. 2004, 4, 110-
119. (b) Fujita, K.; Yorimitsu, H.; Shinokubo, H.; Oshima, K. J. Org. Chem.
2004, 69, 3302-3307. (c) Hayashi, S.; Hirano, K.; Yorimitsu, H.; Oshima,
K. Org. Lett. 2005, 7, 3577-3579. (d) Hayashi, S.; Hirano, K.; Yorimitsu,
H.; Oshima, K. J. Am. Chem. Soc. 2006, 128, 2210-2211.
(5) Rh-catalyzed â-alkynyl elimination with tertiary propargyl alcohols
was reported: (a) Funayama, A.; Satoh, T.; Miura, M. J. Am. Chem. Soc.
2005, 127, 15354-15355. In Rh-catalyzed reactions of cyclobutanones with
aryl boronic acids, ring opening of cyclobutanols via â-carbon elimination
took place. (b) Matsuda, T.; Makino, M.; Murakami, M. Org. Lett. 2004,
6, 1257-1259. Direct observation of â-aryl elimination from iminyl- and
alkoxyrhodium complexes: (c) Zhao, P.; Hartwig, J. F. J. Am. Chem. Soc.
2005, 127, 11618-11619. (d) Zhao, P.; Christopher, D. I.; Hartwig, J. F.
J. Am. Chem. Soc. 2006, 128, 3124-3125.
10.1021/ol060710v CCC: $33.50
© 2006 American Chemical Society
Published on Web 05/13/2006

Scheme 1
Table 2. Sequential Crotylation-Isomerization of Various
Aldehydes via Retro-Allylation
entry
1
4
yield (%)a
We performed the sequential methallylation-isomerization
reaction of an array of aldehydes (Table 1). The reaction of
1b
2
PhCHO (1a)
4a
4b
4c
4d
4e
4f
70
4-MeC6H4CHO (1b)
4-CF3C6H4CHO (1c)
4-MeOC6H4CHO (1d)
4-ClC6H4CHO (1e)
60 (49)
50
3c
4
52
5
51
6
4-PhCOC6H4CHO (1f)
4-MeOCOC6H4CHO (1g)
48 (48)d
64 (59)e
Table 1. Sequential Methallylation-Isomerization of Various
Aldehydes via Retro-Allylation
7b
4g
a Determined by H NMR. Isolated yields are in parentheses. b With 5
mol % of Cs2CO3. c The reaction was carried out in refluxing toluene for
24 h. d R-Adduct, 1-(4-benzoylphenyl)-1-pentanone, was obtained in 3%
yield. e R-Adduct, 1-(4-methoxycarbonylphenyl)-1-pentanone, was obtained
in 3% yield.
1
entry
1
3
yield (%)a
xylene under the same conditions as those for the methallyl
transfer to provide R-substituted ketone 4a in 70% yield.
This regioselectivity strongly suggests that the reaction
involves generation of a σ-crotylrhodium reagent via retro-
allylation.8 Namely, the reaction would proceed via a
mechanism completely different from the Lewis acid-
mediated allyl transfer reactions reported by Nokami and
Loh.9 Other aromatic aldehydes underwent the sequential
crotylation-isomerization. 4-Methylbenzaldehyde (1b) was
converted to the corresponding saturated ketone in 60% yield
(entry 2). The transformations of trifluoromethyl-, methoxy-,
and chloro-substituted benzaldehydes resulted in good yields
(entries 3-5). The reaction of an aldehyde moiety predomi-
nated over that of ketone and ester as observed in the
methallyl transfer (entries 6 and 7).
Allyl and prenyl transfers were also examined (Scheme
2). The sequential allylation-isomerization of benzaldehyde
(1a) with homoallyl alcohol 2c led to low yield. Interestingly,
the reaction with 2d provided the unexpected ketone 6 in
62% yield. The formation of 6 proceeded as follows. The
σ-prenylrhodium A generated via retro-prenylation was
difficult to react with 1a due to steric repulsion at the γ
position. Accordingly, A was isomerized to σ-prenylrhodium
C through π-prenylrhodium B. The following â-H elimina-
tion occurred from C to give rhodium hydride species and
1
2
3
4
5
6
7
4-MeC6H4CHO (1b)
4-CF3C6H4CHO (1c)
4-MeOC6H4CHO (1d)
4-ClC6H4CHO (1e)
4-PhCOC6H4CHO (1f)
4-MeOCOC6H4CHO (1g)
CH3(CH2)10CHO (1h)
3b
3c
3d
3e
3f
3g
3h
79 (66)
73 (65)
85 (77)
71 (54)
66b
91 (68)
70
a Determined by 1H NMR. Isolated yields are in parentheses. b Isolated
yield.
4-methylbenzaldehyde (1b) proceeded smoothly to give the
corresponding saturated ketone 3b in 79% yield (entry 1).
Both electron-deficient and electron-rich aromatic aldehydes
underwent the methallylation-isomerization sequence (en-
tries 2 and 3). Substitution of a chlorine atom on the aromatic
ring did not prevent the reaction (entry 4). Ketone and ester
functionalities were compatible under the reaction conditions
(entries 5 and 6). Aliphatic aldehyde as well as aromatic ones
participated in the reaction. Dodecanal (1h) was converted
to the corresponding saturated ketone 3h in 70% yield (entry
7).
Not only the generation of methallylrhodium but also that
of crotylrhodium could be achieved (Table 2). Benzaldehyde
(1a) was exposed to a solution of homoallyl alcohol 2b in
(6) For convenience, throughout the manuscript, crotylation, methally-
lation, and prenylation are defined as introductions of the 1-methyl-2-
propenyl, 2-methyl-2-propenyl, and 1,1-dimethyl-2-propenyl groups, re-
spectively, into a carbonyl group. On the other hand, the crotyl, methallyl,
and prenyl groups are denoted herein as the 2-butenyl, 2-methyl-2-propenyl,
and 3-methyl-2-butenyl groups, respectively.
(7) Retro-allylations from lithium, magnesium, and zinc alkoxides were
observed. (a) Benkeser, R. A.; Siklosi, M. P.; Mozdzen, E. C. J. Am. Chem.
Soc. 1978, 100, 2134-2139. (b) Gerard, F.; Miginiac, P. Bull. Chim. Soc.
Fr. 1974, 2527-2533. (c) Jones, P.; Knochel, P. J. Org. Chem. 1999, 64,
186-195. Under harsh conditions, retro-allylation took place by the action
of tin: (d) Peruzzo, V.; Tagliavini, G. J. Organomet. Chem. 1978, 162,
37-44. (e) Giesen, V. Dissertation UniVersity Marburg 1989. Ruthenium-
catalyzed deallylation was reported: (f) Kondo, T.; Kodoi, K.; Nishinaga,
E.; Okada, T.; Morisaki, Y.; Watanabe, Y.; Mitsudo, T. J. Am. Chem. Soc.
1998, 120, 5587-5588.
(8) σ-Crotylrhodium is known to react with aldehydes at the γ position.
See ref 2b.
(9) Representative examples: (a) Nokami, J.; Yoshizane, K.; Matsuura,
H.; Sumida, S. J. Am. Chem. Soc. 1998, 120, 6609-6610. (b) Nokami, J.;
Anthony, L.; Sumida, S. Chem.-Eur. J. 2000, 6, 2909-2913. (c) Nokami,
J. J. Synth. Org. Chem. Jpn. 2003, 61, 992-1001. (d) Tan, K.-T.; Chng,
S.-S.; Cheng, H.-S.; Loh, T.-P. J. Am. Chem. Soc. 2003, 125, 2958-2963.
(e) Lee, C.-L. K.; Lee, C.-H. A.; Tan, K.-T.; Loh, T.-P. Org. Lett. 2004, 6,
1281-1283. Also see: (f) Rychnovsky, S. D.; Marumoto, S.; Jaber, J. J.
Org. Lett. 2001, 3, 3815-3818. (g) Crosby, S. R.; Harding, J. R.; King, C.
D.; Parker, G. D.; Willis, C. L. Org. Lett. 2002, 4, 577-580. (h) Samoshin,
V. V.; Smoliakova, I. P.; Hank, M. M.; Gross, P. H. MendeleeV Commun.
1999, 219-221. (i) Horiuchi, Y.; Taniguchi, M.; Oshima, K.; Utimoto, K.
Tetrahedron Lett. 1994, 35, 7977-7980.
2516
Org. Lett., Vol. 8, No. 12, 2006

Scheme 2
Scheme 3
species 8 and homoallyl alcohol 2b with the aid of cesium
carbonate provides the intermediate 9. Retro-allylation then
occurs to generate σ-crotylrhodium, which is in equilibrium
with π-crotylrhodium. Subsequent crotylation of 1a with the
σ-crotylrhodium at the γ position furnishes 10. With PMe3
as a phosphine ligand, alkoxide exchange between 10 and
2b proceeds to produce the secondary homoallyl alcohol 7a
and to regenerate 9. In contrast, use of P(tBu)3 isomerizes
10 to oxa-π-allylrhodium 11 through iterative â-H elimina-
tion-hydrorhodation.11 Finally, ligand exchange between 11
and 2b gives 4a and 9. P(tBu)3-coordinated 10 would undergo
the alkoxide exchange between 10 and 2b less efficiently
than PMe3-coordinated 10.
isoprene. Subsequent hydrorhodation of isoprene followed
by the reaction of 1a with F, which is in σ-π-σ equilibrium
(D-E-F), furnished 6.
The change of the reaction conditions could suppress the
secondary isomerization (Table 3). Treatment of benzalde-
Table 3. Crotylation of Various Aldehydes via
In summary, we have extended the retro-allylation to a
rhodium-catalyzed system and found a new route to the
generation of allylrhodium. In addition, the allylrhodium was
found to have high efficiency in allylation of carbonyl
compounds. Further developments of the retro-allylation
system in other transformations catalyzed by other transition
metals are now in progress.
Retro-Allylation
entry
1
7
yield (%)a erythro/threo
1
PhCHO (1a)
7a
7b
7c
7d
7e
7f
62 (58)
54 (49)
60 (44)
52 (34)
59b
49:51
54:46
56:44
52:48
58:42
56:44c
56:44
2
4-MeC6H4CHO (1b)
4-CF3C6H4CHO (1c)
4-MeOC6H4CHO (1d)
4-ClC6H4CHO (1e)
4-PhCOC6H4CHO (1f)
3
Acknowledgment. This work was supported by Grants-
in-Aid for Scientific Research and COE Research from the
Ministry of Education, Culture, Sports, Science, and Tech-
nology, Japan. K.H. acknowledges JSPS for financial sup-
port.
4
5
6
58b
7d
4-MeOCOC6H4CHO (1g) 7g
65 (59)
a Determined by 1H NMR. Isolated yields are in parentheses. b Isolated
yields. c Tentatively assigned. d With 30 mol % of Cs2CO3.
Supporting Information Available: Detailed experi-
mental procedures and characterization data of compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
hyde (1a, 0.5 mmol) with homoallyl alcohol 2b (1.0 mmol)
in the presence of 2.5 mol % of [RhCl(cod)]2, 10 mol % of
PMe3, and 15 mol % of cesium carbonate in refluxing
dioxane (5.0 mL) for 8 h provided the corresponding
secondary homoallyl alcohol 7a in 62% yield (erythro/threo
) 49:51) (entry 1).10 Electron-deficient and electron-rich
aromatic aldehydes as well as functionalized ones were
converted to the corresponding alcohols in moderate to good
yields (entries 2-7). Unfortunately, no stereoselectivity was
observed in all cases.
OL060710V
(10) Throughout this manuscript, we have adopted the unambiguous
erythro/threo nomenclature proposed by Noyori: Noyori, R.; Nishida, I.;
Sakata, J. J. Am. Chem. Soc. 1981, 103, 2106-2108.
(11) Rh-catalyzed isomerization of unsaturated carbinols: (a) Uma, R.;
Cre´visy, C.; Gre´e, R. Chem. ReV. 2003, 103, 27-52. (b) Sa¨ıah, M. K. E.;
Pellicciari, R. Tetrahedron Lett. 1995, 36, 4497-4500. (c) Shintani, R.;
Okamoto, K.; Hayashi, T. J. Am. Chem. Soc. 2005, 127, 2872-2873. (d)
Yamabe, H.; Mizuno, A.; Kusama, H.; Iwasawa, N. J. Am. Chem. Soc.
2005, 127, 3248-3249.
We are tempted to assume the detailed mechanism as
shown in Scheme 3. Initial ligand exchange between rhodium
Org. Lett., Vol. 8, No. 12, 2006
2517