Notes
J . Org. Chem., Vol. 67, No. 11, 2002 3947
aliphatic ketones from allylic alcohols under a catalytic
system consisting of Wilkinson’s complex, 2-amino-4-
picoline, aniline, and benzoic acid. Allylic alcohols were
employed as a precursor for aliphatic aldehyde, to prevent
aldol condensation, an unfavorable side reaction in
hydroacylation with aliphatic aldehyde. In this reaction,
the chelation-assistance protocol was also effective in
retarding the deactivation of the catalyst through de-
carbonylation of aldehyde intermediate by forming
aldimine.
Exp er im en ta l Section
Gen er a l Meth od . NMR spectra were recorded in CDCl3 at
250 MHz (1H NMR) or 62.5 MHz (13C NMR), and the chemical
shift was expressed in ppm relative to TMS. Unless otherwise
noted, all allylic alcohols, olefins, and amines used in the
experiments were purchased from commercial sources and used
as received. Wilkinson’s complex (RhCl(PPh3)3, 3) was prepared
as described in the literature.12
F igu r e 1. The effect of transimination on the hydroacylation
of 2a with 1a in the presence of 3 (3 mol %), 4 (40 mol %), and
5 (10 mol %), at 130 °C. The results for the reaction with 50
mol % of 13 (2) and without 13 (9) are shown.
Ma ter ia ls. Among allylic alcohols, 2-methyl-3-phenyl-2-pro-
pen-1-ol (1g) and 1-cyclohexenylmethanol (1h ) were prepared
from R-methyl-trans-cinnamaldehyde and 1-cyclohexene-1-car-
boxaldehyde , using lithium aluminum hydride and purified by
column chromatography (SiO2, n-hexane: ethyl acetate ) 5:2).
All the products are known compounds and are easily identified
by 1H NMR, 13C NMR, IR, and mass spectra.
Ta ble 3. A Ch ela tion -Assisted Hyd r oa cyla tion of 2 w ith
1 in th e P r esen ce of 13a
entry
1
2
time (h)
products (yield, %)b
1
2
3
4
5
6
1a
1a
1a
1b
1c
1e
2a
2b
2c
2c
2a
2a
2
2
2
3
2
2
6a (90)
6b (94)
6c (90)
6e (85)
6f (96)
6g (87)
2-Meth yl-3-p h en yl-2-p r op en -1-ol (1 g).13 1H NMR (250
MHz, CDCl3): δ 7.37-7.19 (m, 5H), 6.52 (s, 1H), 4.19 (s, 2H),
2.03 (br s, 1H), 1.90 (s, 3H).13C NMR (62.9 MHz, CDCl3): δ 137.6,
137.5, 128.8, 128.1, 126.4, 124.9, 68.8, 15.2. IR (neat): 3333,
3023, 2916, 2860, 1600, 1491, 1444, 1070, 1010, 842, 698 cm-1
.
a
The reaction was carried out using 1 (0.4 mmol), 2 (1.2 mmol),
4 (0.16 mmol), 5 (0.04 mmol), and 13 (0.2 mmol) in the presence
MS (EI): m/z (relative intensity): 148 (M+, 17), 133 (20), 129
(17), 115 (50), 105 (49), 91 (100), 78 (29), 65 (10), 55 (15), 51
(12), 43 (13).
b
of 3 (0.012 mmol) at 130 °C. The yields are isolated yields.
We have previously demonstrated that the reactivity
of a chelation-assisted hydroacylation with aldehyde was
dramatically improved using a transimination which
facilitates the formation of aldimine (e.g. 8 in Scheme
1).2d,11 Therefore, the effect of transimination was exam-
ined for the reaction of 1a with 2a , by performing the
reaction with or without 50 mol % of aniline 13 (Figure
1).
However, a significant rate enhancement was not ob-
served with the addition of 13. This result implied that
the rate-determining step is not the condensation step
of aldehyde and 4,2e,f but the isomerization of allylic alco-
hol. This result is also in accord with the aforementioned
assumption that the isomerization of allylic alcohol might
be slower than the condensation of aldehyde with 4.
Nevertheless, it was beneficial to utilize a transimi-
nation technique because the yields of products were
slightly increased in the presence of 13 compared with
its absence (Table 3). This might be attributed to the
more facile condensation of aldehyde with 13 than with
4, and the consequent retardation of decarbonylation,
which gave rise to the deactivation of the catalyst. As
shown in Table 3, other allylic alcohols were also allowed
to react with olefins under the transimination condition,
and afforded corresponding ketones in good yields in a
short reaction time compared with the previous reaction
condition.
1-Cycloh exen ylm et h a n ol (1h ).14 1H NMR (250 MHz,
CDCl3): δ 5.67 (br s, 1H), 3.97 (s, 2H), 2.94 (br s, 1H), 2.02-
1.99 (m, 4H), 1.65-1.58 (m, 4H). 13C NMR (62.9 MHz, CDCl3):
δ 137.3, 122.7, 67.2, 25.4, 24.8, 22.4, 22.3. IR (neat): 3482, 2931,
1717, 1450, 1263, 1096, 1072 cm-1. MS (EI): m/z (relative
intensity) 112(M+, 58), 97 (13), 94 (23), 83 (28), 81 (100),
79 (95), 77 (19), 70 (17), 67 (24), 55 (27), 53 (21), 41 (29), 39
(23).
Typ ica l P r oced u r e for a Ca ta lytic Rea ction . Th e Rea c-
tion of Cr otyl Alcoh ol (1a ) a n d 1-Octen e (2b) (Ta ble 1,
en tr y 2). A screw-capped pressure vial (1 mL) was charged with
28.9 mg (0.400 mmol) of crotyl alcohol (1a ), 135 mg (1.20 mmol)
of 1-octene (2b), 17.3 mg (0.160 mmol) of 2-amino-4-picoline (4),
4.9 mg (0.040 mmol) of benzoic acid (5), and 11.1 mg (0.0120
mmol) of RhCl(PPh3)3 (3). It was stirred for 4 h in an oil bath
that was preheated to 130 °C. After the reaction, the mixture
was cooled to room temperature and purified by column chro-
matography (SiO2, n-hexane:ethyl acetate ) 5:2) to yield 63.6
mg (86%) of 4-dodecanone (6b).
4-Dod eca n on e (6b).15 1H NMR (250 MHz, CDCl3): δ 2.38
(t, J ) 7.4 Hz, 2H), 2.37 (t, J ) 7.3 Hz, 2H), 1.64-1.53 (m, 4H),
1.27 (br, 10H), 0.94-0.85 (m, 6H). 13C NMR (62.9 MHz, CDCl3):
δ 211.5, 44.7, 42.8, 31.8, 29.4, 29.3, 29.1, 23.9, 22.6, 17.3, 14.0,
13.7. IR (neat): 2958, 2928, 2856, 1715, 1462, 1414, 1375, 1133,
1027, 736 cm-1. MS (EI): m/z (relative intensity) 184 (M+, 4),
141 (55), 99 (22), 86 (71), 71 (100), 58 (73), 43 (72).
Among the products, 6a ,16 6c,17 6e,18 6f,19 6g,20 6h ,21 6i,22 6j,23
6k ,24 12a ,25 12c,26 and 12d 27 have already been reported and
(12) Osborn, J . A.; Wilkinson, G. In Reagents for Transition Metal
Complex and Organometallic Synthesis; Angelich, R., Ed.; Wiley: New
York, 1989; Vol. 28, pp 77-79.
(13) Daub, G. W.; Edwards, J . P.; Okada, C. R.; Allen, J . W.; Maxey,
C. T.; Wells, M. S.; Goldstein, A. S.; Dibley, M. J .; Wang, C. J .;
Ostercamp, D. P.; Cunningham, P. S.; Berliner, M. A. J . Org. Chem.
1997, 62, 1976.
Con clu sion
In summary, we have applied an efficient chelation-
assisted hydroacylation protocol for the synthesis of
(14) Majetich, G.; Song, J .-S.; Ringold, C.; Nemeth, G. A.; Newton,
M. G. J . Org. Chem. 1991, 56, 3973.
(11) J un, C.-H.; Hong, J .-B. Org. Lett. 1999, 1, 887