Chemistry Letters Vol.33, No.6 (2004)
765
ature, the epoxide-opening reaction with double inversion of the
configuration did occur giving rise to the desired product 2a-syn.
Notably, the reaction was very fast and completed in 10 min at
room temperature, and 2a-syn was obtained in 96% isolated
yield by passing the reaction mixture through a silica gel column
followed by purification.
version of the configuration in excellent yields. The new method
is applicable to various disubstituted cis- and trans-ꢀ,ꢁ-epoxy
unsaturated esters and directly affords vicinal ꢀ,ꢁ-diols in a
highly-stereoselective manner. The method is also applicable
to trisubstituted epoxides, wherein the products including vicinal
secondary and tertiary alcohols are obtainable in high yields.
Since it is known that asymmetric dihydroxylation with chiral
osmium reagents can not be applied to disubstituted cis-olefins,7
the present method provides an extremely useful tool in organic
synthesis including natural product synthesis.
The excellent preliminary results led us to examine the
scope of the new synthetic reaction with various substrates.
The results are summarized in Table 1.5 The reactions of disub-
stituted trans-ꢀ,ꢁ-epoxy-ꢂ,ꢃ-unsaturated esters 1a and 1b pro-
ceeded smoothly to give 2a-syn and 2b-syn in excellent yield,
respectively (Entries 1 and 2). The stereoselectivity of each
product was found to be 98:2 from its 13C NMR spectrum.6 Sim-
ilarly, the corresponding disubstituted cis-congeners also reacted
smoothly to produce the 2a-anti and 2b-anti diols stereospecifi-
cally in 89 and 85% yields, respectively (Entries 3 and 4). Note-
worthy is that the yields of anti-diols derived from cis-epoxides
were much higher than those obtained by the previous method
(Entries 3 and 4). In turn, we examined trisubstituted epoxy un-
saturated esters 4, 6, and 8 prepared from geraniol, nerol, and 2-
methyl-5-phenyl-2-pentenoate, respectively (Entries 5–7).
These substrates also smoothly and cleanly reacted to afford
the corresponding vicinal diols in a highly-stereoselective man-
ner which contain contiguous secondary and tertiary alcohols. It
should be pointed out that the yield of 7 was also improved sub-
stantially by the present method.
To demonstrate the synthetic potential of the present meth-
od, the reactions of 1b with butylboronic acid (BuB(OH)2) and
with B(OH)3 were compared (Scheme 2). Thus, the reaction of
1b with B(OH)3 produced 2b-syn in excellent yield as already
mentioned, whereas the reaction with BuB(OH)2 afforded the
desired cyclic boronate 10 only in moderate yield and unexpect-
ed ketones 11 were formed considerably in the latter reaction.
These results obviously demonstrate that the reaction with
B(OH)3 is much superior to the previous method using
BuB(OH)2.
Pd(II)
RB(OH)
2
H
O
Pd(PPh )
O
3 4
BnO
CO Et
2
BnO
CO Et
2
−
THF, rt
O
B
R
1b
R = Bu, OH
BnO
12
CO Et
2
O
11
Scheme 3. Formation of ketones 11 in the reactions of 1b with
Bu(OH)2 and with B(OH)3.
This work was supported by the Ministry of Education,
Culture, Sports, Science and Technology, Japan (a Grant-in-
Aid for Scientific Research on Priority Areas (A) ‘‘Exploitation
of Multi-Element Cyclic Molecules’’ (No. 13029003)). We are
grateful to High-Resolution NMR Laboratory, Hokkaido
University, for measuring 13C NMR spectra.
References and Notes
1
B. M. Kim, et al., in ‘‘Comprehensive Organic Synthesis,
Additions to C–X ꢄ-Bonds, Part 2,’’ ed. by C. H. Heathcock,
Pergamon Press, Oxford (1991), Vol. 2, Chap. 1.7.
H. Hayakawa, N. Okada, and M. Miyashita, Tetrahedron Lett.,
40, 3191 (1999).
2
3
A. Hirai, T. Tonooka, K. Wakatsuki, K. Tanino, and M.
Miyashita, Chirality, 15, 108 (2003); A. Hirai, X.-Q. Yu, T.
Tonooka, and M. Miyashita, Chem. Commun., 2003, 2482.
trans- and cis-ꢀ,ꢁ-Epoxy unsaturated esters were prepared
from the allyl alcohols by the three step reaction sequence:
1) epoxidation with mCPBA; 2) Swern oxidation; 3) Horner–
Wadsworth–Emmons reaction with triethyl phosphonoacetate.
Typical procedure for the epoxide-opening reaction of ꢀ,ꢁ-
epoxy-ꢂ,ꢃ-unsaturated esters with B(OH)3: To a solution of
1a (53 mg, 0.2 mmol) in THF (1 mL) was added B(OH)3
(27 mg, 0.26 mmol) and Pd(PPh3)4 (12 mg, 0.01 mmol) and
the mixture was stirred at room temperature for 10 min. The re-
action mixture was passed through a silica gel column by the
aid of EtOAc and the eluate was concentrated in vacuo to leave
the crude diol. The crude product was purified by silica gel col-
umn chromatography (hexane/EtOAc = 7:3) to give the 2a-
syn diol (53 mg, 94% yield).
R
B
RB(OH)
BnO
2
BnO
O
Pd(PPh )
3 4
4
5
+
1b
CO Et
2
CO Et
2
THF, rt
11
O
O
R: Bu 59% yield (10)
OH 93% yield (cyclic 2b-syn)
20%
6%
Scheme 2. The reactions of 1b with BuB(OH)2 and with B(OH)3.
Remarkable discrepancy in these reactions may be rational-
ized as follows. As shown in Scheme 3, these reactions proceed
via ꢄ-allyl palladium species 12 wherein a borate anion (R =
OH) acts as an efficient nucleophile to give a cyclic borate (cy-
clic 2b-syn) smoothly, while a boronate anion (R = Bu) proba-
bly does not act as an effective nucleophile due to its steric and/
or electronic factors and consequently undergoes a ꢃ-elimina-
tion reaction concomitantly resulting in the formation of ketones
11. The stability of the cyclic 2b-syn in the reaction is also con-
ceivable.
6
7
Stereochemistry of the products was unambiguously deter-
mined by NOE measurements of the acetonides derived from
2b-syn and 2b-anti, respectively.
L. Wang and K. B. Sharpless, J. Am. Chem. Soc., 114, 7568
(1992); Asymmetric dihydroxylation of dienes, see: D. Xu,
G. A. Crispino, and K. B. Sharpless, J. Am. Chem. Soc., 114,
7570 (1992).
In summary, we have developed a new palladium-catalyzed
epoxide-opening reaction of ꢀ,ꢁ-epoxy-ꢂ,ꢃ-unsaturated esters
with boric acid which gives ꢀ,ꢁ-diol derivatives with double in-
Published on the web (Advance View) May 29, 2004; DOI 10.1246/cl.2004.764