850
P. Gupta et al. / Tetrahedron Letters 45 (2004) 849–851
O
O
O
O
S
O
S
O
O
O
5
ii
i
O
ii
i
6
+
10
12
11
13
4
3
OH
OH
OH
iv
iii
OH
6
O
O
Scheme 1. Reagents and conditions: (i) m-CPBA, CH2Cl2, 0 ꢁC to rt,
10 h, 92%; (ii) R,R-salen–Co-(OAc) (0.5 mol %), distd H2O
(0.55 equiv), 0 ꢁC, 16 h, (45% for 5, 43% for 6).
v
vi
O
O
1b
14
Scheme 3. Reagents and conditions: (i) SOCl2, Et3N, CH2Cl2, 0 ꢁC,
20 min, 99%; (ii) RuCl3, NaIO4, CCl4–MeCN–H2O; 2:2:3, 0 ꢁC, 2 h,
100%; (iii) LiCBCH–ethylene diamine, DMSO, 0 ꢁC to rt, 10 h, 80%;
(iv) H2, Pd/BaSO4, quinoline, benzene, 1 bar, rt, 0.5 h, 86%; (v) acryloyl
chloride, Et3N, CH2Cl2, 0 ꢁC, 5–6h, 84%; (vi) (PCy3)2Ru(Cl)2@CH–Ph
(20 mol %), CH2Cl2, Ti(i-PrO)4, reflux, 12 h, 85%.
The racemic epoxide 4, a substrate for HKR was pre-
pared from commercially available 1-heptene 3 using
m-CPBA. The HKR was performed on 4 with (R,R)-
salen–Co-(OAc) complex 2 (0.5 mol %) and water
(0.55 equiv) to give the R-epoxide 5 in 45% yield
25
D
with >99% ee,14 ½aꢀ +9.6 (c 1, CHCl3) [lit.15 +9.8 (c 1,
CHCl3)] and the S-diol 6 in 43% yield with 99.5% ee,16
25
D
EtOH)] (Scheme 1).
22
D
½aꢀ )15.9 (c 1.67, EtOH) [lit.8a ½aꢀ )15.2 (c 1.67,
that the nucleophilic opening of the cyclic sulfate 11
would occur in a regioselective manner at the terminal
carbon. Indeed the cyclic sulfate 11 on treatment with
lithium acetylide furnished the desired alcohol 12, which
The synthesis of (R)-massoialactone 1a started from the
enantiomerically enriched epoxide 5 as illustrated in
Scheme 2. Thus opening of 5 with an excess of lithium
acetylide followed by partial hydrogenation of the
resultant acetylene 7 with LindlarÕs catalyst furnished
the homoallylic alcohol 8. Compound 8 was esterified
with acryloyl chloride in the presence of triethylamine to
afford 9 in 89% yield. The subsequent ring-closing
metathesis17 in dichloromethane under reflux in high
dilution conditions using the first generation GrubbsÕs
catalyst, bis(tricyclohexylphosphine)benzylidene ruthe-
on hydrogenation followed by ring-closing metathesis
25
D
afforded the target molecule 1b, ½aꢀ +110.1 (c 2.0,
22:6
D
CHCl3) [lit.9 ½aꢀ
+109.6 (c 2, CHCl3)]. The physical
and spectroscopic data were in full agreement with the
literature.8c
In conclusion we have demonstrated that the enantio-
selective synthesis of both the isomers of massoialactone
can be accomplished using hydrolytic kinetic resolution
of a racemic epoxide and ring-closing metathesis. The
synthetic strategy described has significant potential for
further extension to a variety of other 6-substituted
chiral lactones, which serve as important synthons for
several naturally occurring and biologically active
molecules. Currently studies are in progress in this
direction.
nium(IV) dichloride and catalytic amount of Ti(i-PrO)4
25
D
afforded (R)-massoialactone in 84% yield, ½aꢀ )115.2 (c
29
1, CHCl3) [lit.10 ½aꢀ )113.6 (c 1.36, CHCl3)]. The
D
physical and spectroscopic data were in full agreement
with the literature.8c
Scheme 3 summarizes the synthesis of (S)-massoialac-
tone 1b from the diol 6. Thus treatment of 6 with thionyl
chloride in the presence of triethylamine gave the cyclic
sulfite 10, which was further oxidized using NaIO4 and a
catalytic amount of ruthenium trichloride to furnish the
corresponding cyclic sulfate 11 in essentially quantita-
tive yield.18 The essential feature of our synthetic strat-
egy shown in Scheme 3 was based on the presumption
Acknowledgements
P.G. and S.V.N. thank UGC and CSIR New Delhi for
financial assistance, respectively. We are grateful to Dr.
M. K. Gurjar for his support and encouragement. This
is NCL Communication No. 6652.
OH
OH
ii
i
5
References and notes
8
7
O
O
1. Meijer, Th. M. Rec. Trav. Chim. Pays-Bas. 1940, 59, 191–
201.
O
O
iii
iv
2. Crombie, L. J. Chem. Soc. 1955, 1007–1025, 2535.
3. Abe, S. J. Chem. Soc. Jpn. 1937, 58, 246–251.
4. Hashijune, T.; Kikuchi, N.; Sasaki, Y.; Sakata, I. Agric.
Biol. Chem. 1998, 32, 1306–1309.
5. Kaiser, P.; Lamparsky, D. Tetrahedron Lett. 1976, 1659–
1660.
9
1a
Scheme 2. Reagents and conditions: (i) LiCBCH–ethylene diamine,
DMSO, rt, 12 h, 86%; (ii) H2, Pd/BaSO4, quinoline, benzene, 1 bar, rt,
0.5 h, 92%; (iii) acryloyl chloride, Et3N, CH2Cl2, 0 ꢁC, 5–6 h, 89%; (iv)
(PCy3)2 Ru(Cl)2@CH–Ph (20 mol %), CH2Cl2, Ti(i-PrO)4, reflux, 12 h,
84%.
6. Cavill, G. W. K.; Clark, D. V.; Whitfield, F. B. Aust. J.
Chem. 1968, 21, 2819–2823.