The first and highly enantioselective crotylation of aldehydes via an allyl-transfer reaction from a chiral crotyl-donor [3]

Full text of DOI:10.1021/ja011257f

9168
J. Am. Chem. Soc. 2001, 123, 9168-9169
important role together with allyl(ic) metals in determining the
enantioselectivity, requires at least a few steps from naturally
occurring optically pure compounds. The exceptions are (+)-,
(-)-dialkyl tartrate in Roush’s reagents and (+)-, (-)-R-pinene
or (+)-carene in Brown’s reagents,1c,d which can be effectively
used as chiral auxiliaries as they are. In addition, (8) almost all
of the allylation reactions, including the cases using a (3-
substituted)allylmetal reagent, proceed with allylic transposition
and give a (1-substituted)allyl product (e.g. 1-methylallyl adduct).4
No asymmetric (3-substituted)allylation reactions such as croty-
lation reaction to aldehydic carbonyl have been reported.5
The First and Highly Enantioselective Crotylation of
Aldehydes via an Allyl-Transfer Reaction from a
Chiral Crotyl-Donor
Junzo Nokami,* Masanori Ohga, Hitoshi Nakamoto,
Tadahiro Matsubara, Iqbal Hussain, and Kazuhide Kataoka
Department of Applied Chemistry,Okayama UniVersity of
Science, 1-1 Ridai-cho, Okayama 700-0005, Japan
ReceiVed May 22, 2001
The enantioselective allylation of aldehydes is one of the most
popular reactions for constructing homoallylic alcohols with a
chiral center by C-C bond formation.1 This is because the
reaction gives a high enantio excess of homoallylic alcohols,
which provide more functionalized building blocks after func-
tionalizations of the double bond of the introduced allylic unit.
Many methods to prepare highly optically active homoallyl-
(ic) alcohols have been proposed that utilize more than the
stoichiometric amount of allyl(ic) metal compounds in the
presence of a chiral catalyst,1,2 or together with more than the
stoichiometric amount of chiral auxiliaries.1,3 However, in these
asymmetric allylations, a number of problems remain. For
example, in the case of catalytic reactions, (1) Preparation of an
effective catalyst and/or an efficient catalysis system is not easy;
(2) In many cases, more than the stoichiometric amount of
allyl(ic)tributyltin1,2a-d is required as an allyl-donor (in particular,
tributyltin residues are environmentally unfriendly), although
attempts to use allyl(ic)silanes1,2e-h have been made; (3) The
reaction mechanism is not clear in most of the catalytic enanti-
oselective reactions; (4) The degree of enantioselectivity greatly
depends on the substituents of the aldehydic carbon (low substrate
tolerance); (5) Many of the ‘catalytic’ reactions require more than
catalytic amount of chiral ligands (or additives); (6) The reactions
usually have to be performed under precisely controlled reaction
conditions.
These facts prompted us to investigate an asymmetric croty-
lation reaction, which is very convenient to use, has a low cost,
and does not require difficult techiques.
Recently, we discovered6 a new crotylation reaction of aldehyde
2 via an acid-catalyzed allyl-transfer reaction from the 2-methy-
lated-homoallylic alcohol (e.g., 2,3-dimethylpent-4-en-2-ol 1a) to
give the corresponding crotylated product 3, specifically.6a It has
been proposed that the reaction proceeds via the most stable
comformational six-membered cyclic transition state (T1-2) to give
an E-olefin selectively, while maintaining the optical purity
(>98% ee).6b The reaction is shown in Scheme 1.
This result strongly suggested that we would be able to provide
the first efficient enantioselective crotylation reaction, if we could
conveniently prepare an enantiomerically or diasteromerically pure
crotyl-donor.
We thus examined (1-methyl)allylation of (-)-menthone 4,7
derived from the artificial (-)-menthol (>99% purity),8 by a
Grignard reaction with (E)-crotylmagnesium chloride to give 5a
in a sterically pure form after separation of the diastereoisomeric
mixture in good isolated yield (77%).9 The major product (R)-5a
(assignment by analogy) was then used as a crotyl-donor in an
allyl-transfer reaction with 3-phenylpropanal in the presence of
acid-catalyst. Surprisingly, we discovered that (5E,3R)-1-phenyl-
hept-5-en-3-ol 3a6b was obtained in good yield with very high
e.e., as shown in Scheme 210 (Table 1), when p-toluenesulfonic
acid monohydrate (TSA‚H2O) served as an effective catalyst.6
Moreover, in the case of noncatalytic reactions,1,3 (7) the
preparation of an effective chiral auxiliary, which plays an
(1) For reviews on the reaction using allyl(ic) metals, (a) Yamamoto, Y.;
Asao, N. Chem. ReV. 1993, 93, 2207. (b) Marshall, J. A. In Lewis Acids in
Organic Synthesis Vol. 1. Yamamoto, H., Ed.; Willey-VCH: New York. 2000.
For reviews on asymmetric allylation and related reactions, (c) Denmark, S.
E.; Almstead, N. G. In Modern Carbonyl Chemistry; Otera, J., Ed.; Willey-
VCH: New York, 2000. (d) Chemler, S. R.; Roush, W. R. In Modern Carbonyl
Chemistry; Otera, J., Ed.; Willey-VCH: New York, 2000.
(2) Allyltributyltin with chiral catalyst, (a) Doucet, H.; Santelli, M.
Tetrahedron: Asym. 2000, 11, 4163. (b) Loh, T.-P.; Zhou, I.-R. Tetrahedron
Lett. 2000, 41, 5261. (c) Motoyama, Y.; Narusawa, H.; Nishiyama, H. J. Chem.
Soc., Chem. Commun. 1999, 131. Excess tetraallyltin with chiral catalyst
(allylation of ketones), (d) Casolari, S.; D′Addario, D.; Tagliavini, E. Org.
Lett. 1999, 1, 1061. Allylsilane with chiral catalyst, (e) Denmark, S. E.; Fu,
J. J. Am. Chem. Soc. 2000, 122, 12021. (f) Yanagisawa, A.; Kageyama, H.;
Nakatsuka, Y.; Asakawa, K.; Matsumoto, Y.; Yamamoto, H. Angew. Chem.,
Int. Ed. Engl. 1999, 38, 3701. (g) Iseki, K.; Mizuno, S.; Kuroki, Y.; Kobayashi,
Y. Tetrahedron Lett. 1998, 39, 2767. (h) Nakajima, M.; Saito, M. J. Am. Chem.
Soc. 1998, 120, 6419. Allylbromide and metallic Mn with chiral Cr(II)[salen]-
catalyst, (i) Bandini, M.; Cozzi, P. G.; Melchiorre, P.; Umani-Ronchi, A.
Angew. Chem., Int. Ed. Engl. 1999, 38, 3357.
(3) Chiral B-allylborane, (a) ref 1d. (b) Williams, D. R.; Clark, M. P.; Emde,
U.; Berliner, M. A. Org. Lett. 2000, 2, 3023. Allyltin having chiral ligand,
(c) Otera, J.; Yoshinaga, Y.; Yamaji, T.; Yoshioka, T.; Kawasaki, Y. Organo-
metal. 1985, 4, 1213. Allyltin with a chiral auxiliary, (d) Mukaiyama, T.;
Minowa, N.; Oriyama, T.; Narasaka, K. Chem. Lett. 1986, 97. (e) Boldrini,
G. P.; Lodi, L.; Tagliavini, Tarasco, C.; E.; Trombini, C.; Umani-Ronchi, A.
J. Org. Chem. 1987, 52, 5447. (f) Boga, C.; Savoia, D.; Tagliavini, E.;
Trombini, C.; Umani-Ronchi, A. J. Ogranometal. Chem. 1988, 353, 177. (g)
Kobayashi, S.; Nishio, K. Tetrahedron Lett. 1995, 36, 6729. (h) Yamada, K.;
Tozawa, T.; Nishida, M.; Mukaiyama, T. Bull. Chem. Soc. Jpn. 1997, 70,
2301. Allyl bromide and metallic In with a chiral auxiliary, (i) Loh, T.-P.;
Zhou, J.-R.; Yin, Z. Org. Lett. 1999, 1, 1855. (j) Loh, T.-P.; Zhou, J.-R. Tetra-
hedron Lett. 1999, 40, 9115. (k) Loh, T.-P.; Zhou, J.-R. Tetrahedron Lett.
1999, 40, 9333. Allyltitanium complexed with a chiral auxiliary, (l) Bouzbouz,
S.; Cossy, J. Org. Lett. 2000, 2, 501. (m) Bouzbouz, S.; Popkin, M. P.; Cossy,
J. Org. Lett. 2000, 2, 3449. (n) Cossy, J.; Willis, C.; Bellosta, V.; Bouzbouz,
S. Synlett 2000, 1461. Allylsilane with chiral auxiliary, (v) Denmark, S. E.;
Coe, D. M.; Pratt, N. E.; Griedel, B. D. J. Org. Chem. 1994, 59, 6161. (w)
Zhang, L. C.; Sakurai, H.; Kira, M. Chem. Lett. 1997, 129.
(4) In various allylation reactions of aldehydes utilizing allylic metal
reagents, an allylic barium compound seems to be one of the most exceptional
reagents which selectively gives (3-substituted)allyl adducts, (a) Yanagisawa,
A.; Habaue, S.; Yamamoto, H. J. Am. Chem. Soc. 1991, 113, 8955. (b)
Yanagisawa, A.; Habaue, S.; Yasue, K.; Yamamoto, H. J. Am. Chem. Soc.
1994, 116, 6130.
(5) Asymmetric 1-methylallylation and related reactions: By chiral catalyst
with tributylcrotyltin, (a) Marshall, J. A.; Tang, Y. Synlett 1992, 653. By chiral
catalyst with crotylsilane, (b) Yanagizawa, A.; Kageyama, H.; Nakatsuka, Y.;
Asakawa, K.; Matsumoto, Y.; Yamamoto, H. Angew. Chem., Int. Ed. Engl.
1999, 38, 3701. (c) Aoki, S.; Mikami, K.; Terada, M.; Nakai, T. Tetrahedron
1993, 49, 1783. (d) Furuta, K.; Mouri, M.; Yamamoto, H. Synlett 1991, 561.
(e) Iseki, K.; Mizuno, S.; Kuroki, Y.; Kobayashi, Y. Tetrahedron Lett. 1998,
39, 2767. (f) Nakajima, M.; Saito, M. J. Am. Chem. Soc. 1998, 120, 6419. By
Cr(II)[salen]-catalyst with crotyl bromide and metallic Mn, (g) Bandini, M.;
Cozzi, P. G.; Umani-Ronchi, A. Angew. Chem., Int. Ed. Engl. 2000, 39, 2327.
Noncatalytic reaction with stoichiometric amount of chiral B-crotylborane
reagents, (h) Roush, W. R.; Halterman, R. L. J. Am. Chem. Soc. 1986, 108,
294. (i) Roush, W. R.; Ando, K.; Powers, D. B.; Halterman, R. L.; Palkowitz,
A. D. Tetrahedron Lett. 1988, 29, 5579. (j) Garcia, J.; Kim, B. M.; Masamune,
S. J. Org. Chem. 1987, 52, 4831. (k) Brown, H. C.; Jadhav, R. K. Tetrahedron
Lett. 1984, 25, 1215. (l) Brown, H. C.; Bhat, K. S. J. Am. Chem. Soc. 1986,
108, 293.
(6) (a) Nokami, J.; Yoshizane, K.; Matsuura, H.; Sumida, S. J. Am. Chem.
Soc. 1998, 120, 6609. (b) Sumida, S.; Ohga, M.; Mitani, J.; Nokami, J. J.
Am. Chem. Soc. 2000, 122, 1310. (c) Nokami, J.; Anthony, L.; Sumida, S.
Chem. Eur. J. 2000, 6, 2909.
(7) Commercially available (-)-menthone (90% purity, containing ca. 5%
of isomenthone) was unsuitable for our purpose, because it reacted with
crotylmagnesium chloride to give a mixture of inseparable stereoisomers of
the crotyl-donors (5), which gave 3a in 90-95% ee.
(8) Both enantiomers are prepared by PCC- or Dess-Martin-oxidation
of the corresponding menthols (>99%), which are inexpensively available
by Noyori’s chemistry; Tani, K.; Yamagata, T.; Otsuka, S.; Akutagawa, S.;
Kumobayashi, H.; Taketomi, T.; Takaya, H.; Miyashita, A.; Noyori, R. J.
Chem. Soc., Chem. Commun. 1982, 600.
10.1021/ja011257f CCC: $20.00 © 2001 American Chemical Society
Published on Web 08/24/2001

Communications to the Editor
J. Am. Chem. Soc., Vol. 123, No. 37, 2001 9169
Table 2. Reaction of (R)-5a with Various Aldehydesa
Scheme 1. Crotylation of Aldehydes via Allyl-Transfer
Reaction from Crotyl-Donor 1a to Aldehydes 2
entry
2
R
3
yieldb (%) %ee(config.)c
1d
2
3
4
5
6
7
8
b
c
d
e
f
g
h
i
Ph
b
c
d
e
f
g
h
i
48
75
64
78
71
71
0
>99e (S)
>99e (R)
>99e (S)
>99e (S)
>99f (S)
>99f (R)
-
BnO(CH2)5
PhCH(CH3)
PhS(CH2)2
(CH3CH2)2CH
CH2dCH(CH2)8
citroneral
Scheme 2. Asymmetric Crotylation of Aldehyde 2a
CH3(CH2)4CHdCH
0
-
a All the reactions were performed with (R)-5a (1.0 mmol) and 2
(0.5 mmol) in the presence of 10 mol % of TSA‚H2O in CH2Cl2 (5
mL), at 20 °C for 20 h unless otherwise noted. b Isolated yield based
on the aldehyde. c Assignment by analogy based on the configuration
of 3a. d Performed in 2.5 mL of CH2Cl2. e Determined by HPLC
f
analysis (CHIRALCEL OD, 5% i-PrOH in hexane as eluent).
Determined by HPLC analysis (CHIRALCEL AD, 5% i-PrOH in
hexane as eluent) of the corresponding MTPA ester derived from (+)-
MTPA.
quantity of water (e.g. 1 equiv to aldehyde) did not prevent the
reaction, and only slightly reduced the yield (entry 5). Moreover,
we surprisingly found that the crude (R)-5a (71% de) gave
(5E,3R)-3a in satisfactory yield with 97% ee.11 On the other hand,
(5E,3S)-3a was obtained in 88% yield with >99% e.e. from the
enantiomer of (R)-5a, derived from (+)-menthol.
The reaction with various aldehydes also gave the correspond-
ing crotyl products in good yield and in high e.e. with a few
exceptions, as shown in Table 2. Citoronellal was fast converted
to 2-isopropylidene-5-methylcyclohexanol, isopuregol, via acid-
catalyzed cyclization (entry 7). R,â-Unsaturated aldehyde did not
react with the crotyl-donor 5a (or with 1a) (entry 8). In the case
of R is R′-CHdCH in RCHO, we assume that the oxonium ion
T3 (T1) is too stable to give T4 (T2). This is because the cation,
T3 (T1) will be highly stabilized by a conjugation with the
neighboring π-bond.
Finally, we attempted to apply this concept to an asymmetric
allylation of aldehydes. Optically pure 1-allylmenthol (6a, >99%
ee, 1 mmol) was treated with 3-phenylpropanal (2a, 0.5 mmol)
for 2, 5, 10, and 15 h, in the presence of TSA‚H2O (10 mol %)
in CH2Cl2 (5 mL) at 20 °C. We obtained (R)-1-phenylhex-5-en-
1-ol (7) in 50% (78% e.e.), 60% (71% e.e.), 68% (70% e.e.), and
72% (68% e.e.) chemical and optical yields, respectively. This
means that the asymmetric allylation by an allyl-transfer reaction
is not as easy as the asymmetric crotylation.12
Table 1. Reaction of (R)-5a with 3-phenylpropanal (2a)a
(R)-5a/mmol recovery of
catalystb
run (equiv. to 2a) (equiv. to 2a) 3a yieldc/% %eed (R)-5a/%e
1
0.5 (1)
1.0 (2)
1.0 (2)
0.5 (0.5)
1.0 (2)
1.0 (2)
1.0 (2)
1.0 (2)
1.0 (2)
1.0 (2)
TSA‚H2O (0.1)
TSA‚H2O (0.1)
TSA‚H2O (0.1)
TSA‚H2O (0.1)
TSA‚H2O (0.1)
N-HOBSA (1.0)
BSA (0.1)
62
83
53
67g
71
34
82
83
39
31
>99
>99
>99
>99
>99
>99
>99
>99
97
39 (14)
55
56 (40)
16 (39)
2
3f
4
5h
6i
7
39
45
8
9
10
CSA (0.8)
49
Sn(OTf)2 (0.4)
53
Sn(OTf)2 (0.4)j
97
70 (10)
a The reaction was performed in CH2Cl2 (5 mL), at 20 °C, for 20 h
unless otherwise noted. b Camphorsulfonic acid (CSA), N-hydroxy-
benzenesulfonamide (N-HOBSA), p-toluenesulfonic acid monohydrate
(TSA‚H2O), benzenesulfonic acid (BSA). c Isolated yield based on 2a,
except run 4. d Determined by HPLC analysis (CHIRALCEL OD, 5%
PriOH in hexane as eluent. e Recovery of 2a was shown in parentheses
(%). f Performed at 0 °C. g Isolated yield based on (R)-5a. h In the
presence of H2O (0.5 mmol). i Performed in (CH2Cl)2 (5 mL) at 65
°C. j In the presence of MS4 Å (25 mg).
It is noteworthy that the degree of asymmetric induction (%
e.e.) was constantly very high throughout the investigation, and
the highest yield was recorded when TSA‚H2O was used as a
catalyst. The handling of this reaction was quite easy. That is, to
a solution of (R)-5a and 3-phenylpropanal (2a) in dichloromethane
was added TSA‚H2O (10 mol %) at 20 °C and the reaction mixture
was gently stirred for 20 h under nitrogen. An excess amount (2
equiv to aldehyde) of (R)-5a was required to give 3a in good
(83%) yield. The unreacted (R)-5a, however, could be recovered
in a pure form and was used again for the same reaction. A small
We believe that the allyl-transfer reported here is the first and
highly enantioselective crotylation of aldehydes, and introduces
the following advantages. Both of the enantiomers of the chiral
crotyl-donors are very easily obtained by the Grignard reaction
with (-)- or (+)-menthones derived from the corresponding
menthols. The reagents are very easy to handle, and are
environmentally friendly.
Acknowledgment. This study was supported by a Grant in Aid for
Scientific Reserch from the Ministry of Education, Science, Culture, and
Sports, Japan (No. 12450357).
Supporting Information Available: Experimental procedures and
complete characterization (1H and 13C NMR, IR, and mass spectra) for
compounds, 3b-g, 4, 5a-b, and 6a, the stereochemistry of (R)-5a, the
racemization of (R)-7, and some additional references. This material is
available free of charge via the Internet at http://pubs.acs.org.
(9) Diastereoselective additions of carbon nucleophiles to optically active
ketones, such as menthone, and their applications for asymmetric synthesis
have been reported; (a) Johnson, C. R.; Stark, C. J. Jr. Tetrahedron Lett. 1979,
4713. (b) Chillous, S. E.; Hart, D. J.; Hutchinson, D. K. J. Org. Chem. 1982,
47, 5418. (c) Jauch, J.; Schurig, V. Tetrahedron: Asym. 1997, 8, 169. (d)
Spino, C.; Beaulieu, C. Angew. Chem., Int. Ed. Engl. 2000, 39, 1930. (e)
Davis, A. P. Angew. Chem., Int. Ed. Engl. 1997, 36, 591. (f) Harada, T.;
Hayashiya, T.; Wada, I.; Iwa-ake, N.; Oku, A. J. Am. Chem. Soc. 1987, 109,
527. (g) Harada, T.; Oku, A. Synlett 1994, 95, and references therein.
(10) A referee suggested an alternative explanation involving acyclic
transition states. However, the methyl ether of (R)-5a was quantitatively
recovered after treatment of the ether with 2a at 20 °C for 24 h in CH2Cl2 in
the presence of 10 mol % of TSA‚H2O. This shows that the formation of
JA011257F
(11) In addition to (R)-5a, the crude product contained the diastereoisomer
(S)-5a and 1-crotylmenthol. We are assuming that (R)-5a will be more reactive
with aldehyde than the isomer(s).
(12) This means that (R)-7 served as an allyl-donor under the reaction
conditions to give racemic 7 by an allyl-transfer reaction of the allyl-unit of
(R)-7 into 2a via the six-membered chair-form transition state. This is discussed
in the Supporting Information.
hemiacetal (H2) and the sequential six membered cyclic transition state (T3-4
)
is essential for this allyl-transfer reaction.