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.
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Org. Lett., Vol. 8, No. 12, 2006