New concept in the allylation of aldehydes: Regiospecific allylation of aldehydes by an allyl-transfer reaction of homoallylic alcohols

Full text of DOI:10.1021/ja9810742

J. Am. Chem. Soc. 1998, 120, 6609-6610
6609
Scheme 1
New Concept in the Allylation of Aldehydes:
Regiospecific Allylation of Aldehydes by an
Allyl-Transfer Reaction of Homoallylic Alcohols
Junzo Nokami,* Kenji Yoshizane, Hiroyuki Matsuura, and
Shin-ichi Sumida
Department of Applied Chemistry
Okayama UniVersity of Science
Ridai-cho 1-1, Okayama 700-0005, Japan
Scheme 2
ReceiVed March 31, 1998
Allylation of carbonyl compounds with allylic organometallic
reagents is one of the most fundamental and important reactions
for constructing carbon-carbon bonds.1 For example, Grignard-
and Barbier-type reactions have been widely utilized for the
allylation of aldehydes and ketones, in which chemo-, regio-, and
stereoselectivities of the desired homoallylic alcohols are highly
dependent on the nature of the metals employed. On the other
hand, carbonyl-ene reactions constitute a more efficient alterna-
tive to the carbonyl addition reactions of allylic metals,2 although
the type of carbonyl enophiles that can be used is limited, e.g.
formaldehyde, chloral, and glyoxylate.
Herein, we disclose a conceptually new allylation of alde-
hydes: an allylic functionality of the homoallyl alcohol 2a is
transferred to the aldehyde 1a to give the desired homoallylic
alcohol 3 in the presence of a catalytic amount of Sn(OTf)2
(Scheme 1).
First, the allylation of 1a with 2b in the presence of various
catalysts was examined (Table 1). The reaction of 1a with 2b in
the presence of a catalytic amount of tin(II) triflate (10 mol %)
in dichloromethane at room temperature for 6 h was carried out
to afford a 9:1 mixture of E- and Z-isomers of 1-phenyl-5-hepten-
3-ol 4a in 90% yield (entry 1). Addition of molecular sieves 4
Å powder to the reaction media led to an improved yield of 4a
(95%) and a lower reaction temperature (-25 °C) (entry 2). Even
with the molecular sieves 4 Å powder, zinc(II) triflate was less
effective (entry 3) and the reaction with silver(I) triflate failed
(entry 4). It is of interest to note that N-hydroxybenzenesulfona-
mide, which has been used as a mild acid for the acetalization of
Peruzzo,3 Gambaro,4 and Nokami5 reported that Grignard- and
Barbier-type additions of carbonyls with allyltin halides to tin
homoallyl alcoholates were reversible processes. Therefore, the
formation of the homoallylic alcohol 3 might be explained by
assuming that an allyltin species, generated by retro-allylation3-5
of the original homoallyl alcohol 2a with tin(II) triflate, promotes
a Grignard-type allylation of 3-phenylpropanal 1a.
To investigate this further, we performed the allylation with
2,3-dimethyl-4-penten-2-ol 2b, as shown in Scheme 2. Surpris-
ingly, the reaction of 1a with 2b proceeded in a completely
regioselective manner to afford an unexpected R-adduct 1-phenyl-
5-hepten-3-ol 4a without any detectable amount of the γ-adduct
7.6 This result strongly suggests that the crotyltin species 6 would
not be formed by the reaction of 2b with tin(II) triflate (path B
in Scheme 2), as it is well-known that most allylic metal
compounds such as 6 react with carbonyls to give γ-adducts such
as 7, predominantly or exclusively.1
aldehydes with alcohols,8
gave the desired alcohol 4a (40%)
although a high temperature (80 °C) was required (entry 5).
By using tin(II) triflate and molecular sieves 4 Å powder, the
allylation of aldehydes 1a-f with 2b in dichloromethane afforded
the expected R-adducts 4a-f in high yields (70-97%) and
stereoselectivities (E/Z ) 6/1 to 12/1) (Table 2).
To gain some information on the Sn(II)-catalyzed allylation
mechanism, a reaction with other homoallylic alcohols 2 was
investigated (Table 3). The reaction of 1a with 2-methyl-3-
phenyl-4-penten-2-ol 2c took place in a stereoselective fashion
to afford only (5E)-1,6-diphenyl-5-hexen-3-ol 4g (99%) without
any detectable amount of its Z-isomer (entry 2). 2,3,3-Trimethyl-
4-penten-2-ol 2e gave the corresponding homoallylic alcohol 4i
(51%) although excess amounts of 2e were required (entry 4).
The exclusive formation of the R-adducts 4 (Tables 1-3) and
the promotion of the desired allylation by N-hydroxybenzene-
sulfonamide (Table 1, entry 5) proved that tin(II) triflate did not
act in the formation of the allylic tin compounds such as 6, by
retro-allylation with the homoallylic alcohols 2. This leads us to
propose a new mechanism, as shown in Scheme 3.
On this basis, we propose the first synthesis of R-adducts of
homoallylic alcohols 4 through an allyl-transfer reaction from the
γ-adducts of homoallylic alcohols 2, derived from acetone,7 to
the aldehydes 1.
(1) Reviews: (a) Courtois, G.; Miginiac, L. J. Organomet. Chem. 1974,
69, 1. (b) Biellmann, J. F.; Ducep, J. B. Org. React. 1982, 27, 1. (c) Roush,
W. R. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I.,
Heathcock, C. H., Eds.; Pergamon Press: Oxford, U.K., 1991; Vol. 2, p 1.
(d) Yamamoto, Y.; Asao, N. Chem. ReV. 1993, 93, 2207.
In the initial stage of the reaction, the formation of the carbo-
cation 9A occurs through hemiacetalization of 1 and 2 to 8 with
the aid of tin(II) triflate.9 Due to the differences in stabilization
between the three kinds of cation species 9A-C, the rearrange-
(2) Mikami, K.; Shimizu, M. Chem. ReV. 1992, 92, 1021.
(3) Peruzzo, V.; Tagliavini, G. J. Organomet. Chem. 1978, 162, 37.
(4) Gambaro, A.; Marton, D.; Peruzzo, V.; Tagliavini, G. J. Organomet.
Chem. 1981, 204, 191.
(5) Nokami, J.; Otera, J.; Sudo, T.; Okawara, R. Organometallics 1983, 2,
191.
(7) Among the various kinds of homoallylic alcohols used as an allyl donor,
those derived from 2-butanone, cyclohexanone, and cyclopentanone had a
similar effect to that derived from acetone. However, sterically more hindered
homoallylic alcohols were less reactive.
(8) Hassner, A.; Wiederkehr, R.; Kascheres, A. J. J. Org. Chem. 1970, 35,
1962.
(9) (a) Gambaro, A.; Boaretto, A.; Marton, D.; Tagliavini, G. J. Organomet.
Chem. 1983, 254, 293. (b) Boaretto, A.; Marton, D.; Tagliavini, G. Inorg.
Chim. Acta 1983, 77, L153. (c) Gambaro, A.; Furlani, D.; Marton, D.;
Tagliavini, G. J. Organomet. Chem. 1986, 299, 157. (d) Wei, Z. Y.; Li, J. S.;
Wang, D.; Chan, T. H. Tetrahedron Lett. 1987, 28, 3441. (e) Wei, Z. Y.;
Wang, D.; Li, J. S.; Chan, T. H. J. Org. Chem. 1989, 54, 5768. (f) Coppi, L.;
Ricci, A.; Taddei, M. Tetrahedron Lett. 1987, 28, 973. (g) Coppi, L.; Ricci,
A.; Taddei, M. J. Org. Chem. 1988, 53, 911. (h) Marko´, I. E.; Chelle´, F.
Tetrahedron Lett. 1997, 38, 2895.
(6) Some methods for the synthesis of R-adducts 4 using allylic organo-
metallic reagents have been reported: (a) Gambaro, A.; Gains, P.; Marton,
D.; Peruzzo, V.; Tagliavini, G. J. Organomet. Chem. 1982, 231, 307. (b)
Gambaro, A.; Boaretto, A.; Marton, D.; Tagliavini, G. J. Organomet. Chem.
1984, 260, 255. (c) Miyake, H.; Yamamura, K. Chem. Lett. 1992, 1369. (d)
McNeill, A. H.; Thomas, E. J. Tetrahedron Lett. 1992, 33, 1369. (e) Kanagawa,
Y.; Nishiyama, Y.; Ishii, Y. J. Org. Chem. 1992, 57, 6988. (f) Yamamoto,
Y.; Maeda, N.; Maruyama, K. J. Chem. Soc., Chem. Commun. 1983, 742. (g)
Yamamoto, Y.; Maruyama, K. J. Org. Chem. 1983, 48, 1564. (h) Guo, B. S.;
Doubleday: W.; Cohen, T. J. Am. Chem. Soc. 1987, 109, 4710. (i) Iqubal, J.;
Joseph, S. Tetrahedron Lett. 1989, 30, 2421. (j) Yanagisawa, A.; Habaue, S.;
Yamamoto, H. J. Am. Chem. Soc. 1991, 113, 8955. (k) Yanagisawa, A.;
Habaue, S.; Yasue, K.; Yamamoto, H. J. Am. Chem. Soc. 1994, 116, 6130.
S0002-7863(98)01074-9 CCC: $15.00 © 1998 American Chemical Society
Published on Web 06/17/1998

6610 J. Am. Chem. Soc., Vol. 120, No. 26, 1998
Table 1. Effect of Catalysts for Allylation of 1a with 2ba
Communications to the Editor
Scheme 3
MS-4Ab
(mg)
Temp
(°C)
isolated yield (%)
entry
catalyst
4a (E/Z)c
1a
1
Sn(OTf)2
Sn(OTf)2
Zn(OTf)2
AgOTf
r.t.
90 (9/1)
95 (12/1)
24 (10/1)
2
50
50
50
-25
3
r.t.
56
quant
42
4
r.t.
5d
PhSO2NHOH
80
40 (5/1)
a All reactions were performed with 1a (1 mmol), 2b (1.5 mmol),
and catalyst (0.1 mmol) in CH2Cl2 (5 mL) for 6 h, unless otherwise
noted. b Molecular sieves 4Å powder. c Ratios were determined by 1H
NMR (500 MHz) integration of the mixture. d CH3CN (5 mL) was used
as solvent.
Table 2. Allylation of Aldehydes 1 with
2,3-Dimethyl-4-penten-2-ol 2ba
entry
aldehyde 1 R
T (°C) t (h) yieldb (%) ratio (E/Z)
Scheme 4
1
PhCH2CH2 (1a)
Ph (1b)
p-NO2C6H4 (1c)
m-MeOC6H4 (1d)
n-C5H12 (1e)
t-Bu (1f)
-25
-25
r.t.
6
8
6
8
2
6
95 (4a)c
94 (4b)e
97 (4c)
88 (4d)
86 (4e)h
70 (4f)e
12/1d
11/1f
6/1f
2
3g
4
r.t.
8/1f
5
6
-25
9/1f
-25
10/1f
a All reactions were performed with 1 (1 mmol), 2b (1.5 mmol),
Sn(OTf)2 (0.1 mmol), and molecular sieves 4Å powder (50 mg) in
CH2Cl2 (5 mL), unless otherwise noted. b Isolated yield. c Reference
1
11a. d Ratios were determined by H NMR (500 MHz) integration of
the mixture. e Reference 6a. f Ratios were determined by 1H NMR (300
MHz) integration of the mixture. g Sn(OTf)2 (20 mol%) was used.
h Reference 6e and 6k.
Scheme 4. In the case of 2b, the transition state 11 is preferable
to 12 due to the minimization of 1,3-diaxial repulsion between
the methyl substituent and hydrogen atom of the terminal olefin.
Therefore, the E-isomers of 4a-h are formed as major products
(Tables 1-3). In particular, the homoallylic alcohol 2c affords
the remarkable E selectivity because the steric hindrance is
appreciably increased by a phenyl group (Table 3, entry 2). In
the case of 2e, since the 1,3-diaxial repulsion always exists, excess
amounts of 2e are required for promotion of the desired allylation
(Table 3, entry 4).
Although the reaction mechanism is not completely clear, we
can assume that the reaction is accelerated to give (i) a more
stable cation, (ii) a sterically less hindered homoallylic alcohol,
and (iii) thermodynamically more stable olefins.
Further study to clarify the reaction mechanism and show the
synthetic utility of the Sn(II)-catalyzed allylation is now in
progress.
Table 3. Allylation of 3-Phenylpropanal 1a with Homoallylic
Alcohols 2a
homoallylic alcohol 2
entry
R1
R2
R3
isolated yield (%, E/Z)
1
Me
H
H (2b)
H (2c)
H (2d)
H (2e)
H (2a)
Me (2f)
95 (12/1)b (4a)
99 (E only)c (4g)
87 (E only)c (4h)
51 (4i)
2
Ph
H
3
CO2Et
Me
H
H
4d
5
Me
H
79 (3)
6
H
H
8 (4j)e,f
a All reactions were performed with 1a (1 mmol), 2 (1.5 mmol),
Sn(OTf)2 (0.1 mmol), and molecular sieves 4Å powder (50 mg) in
CH2Cl2 (5 mL) at -25 °C, unless otherwise noted. b Ratios were
determined by 1H NMR (500 MHz) integration of the mixture. c Z
isomer could not be detected by 1H NMR (300 MHz). d 1a was treated
with 2d (3.0 mmol). e Reference 11b. f See footnote 10.
Acknowledgment. This work was financially supported by a Grant
in Aid for Scientific Research from the Ministry of Education, Science,
Culture, and Sports, Japan, and a Grant for Cooperative Research
administered by the Japan Private School Promotion Foundation.
Supporting Information Available: Preparation information and
characterization data for 3 and 4a-j (5 pages, print/PDF). See any current
masthead page for ordering information and Web access instructions.
ment of 9A produces the most stable cation 9C, which in turn
reacts with a hydroxyl equivalent generated in situ to give the
R-adduct 4 together with acetone via the hemiacetal 10. This
explains the low yield of 4j, i.e., the cation 9B (R1 ) R2 ) H, R3
) Me in Scheme 3), generated from 2f, is stabilized by an
electron-donating methyl substituent, and so the rearrangement
of 9B to 9C is almost completely prevented (Table 3, entry 6).10
Although the role of the molecular sieves 4 Å powder is not clear
at present, it is possible that it plays an important role in the
dehydroxylation of the hemiacetal 8 and the hydroxylation of the
carbocation 9C by a hydroxyl source (Table 1, entries 1 and 2).
The Sn(II)-catalyzed allylation of 1 and 2 gave predominantly
the E homoallylic alcohols 4. The result can be explained by
cyclic chairlike transition-state models 11 and 12, as shown in
JA9810742
(10) In the crude products, a considerable amount of 13 and/or 14, which
would be formed by removal of proton from stable carbocation 9B derived
by the treatment of 2f with 1a, were detected by GC-MS.
(11) (a) Inomata, K.; Igarashi, S.; Mohori, M.; Yamamoto, T.; Kinoshita,
H.; Kotake; H. Chem. Lett. 1987, 707. (b) Minowa, N.; Mukaiyama, T. Bull.
Chem. Soc. Jpn. 1987, 60, 3697.