C O M M U N I C A T I O N S
Scheme 3
as the ligand, the reaction of (2S,5R)-7a provided the desired cyclo-
isomerization product (2R,3S)-8a in 100% conversion and over 99%
ee in 2 min. Reaction of (2R,5S)-7a did not occur under the same
conditions. These results reveal that the stereoselectivity of the kine-
tic resolution is outstanding. In addition, the reactions confirm the ex-
cellent recognization between the ligand and substrates. On the basis
of the results, we conclude that that the path B is preferred over
path A in Scheme 2, which means (R)-reactants match (S)-BINAP.
Scheme 4
To distinguish the controlling factor of the excellent stereose-
lectivity, we examine the reaction of 9 under the similar reaction
conditions. The kinetic resolution result is poor. A diastereoisomeric
mixture was obtained, and both the ee values of the diastereoisomers
are over 99%.
In summary, a highly stereoselective kinetic resolution of enynes
and Rh(I)-catalyzed intramolecular cycloisomerization reaction were
developed. Polyfunctionalized tetrahydrofurans with two adjacent
stereogenic centers and high ee values of enynes were obtained in
this process. Syntheses of more complex molecules are currently
under investigation in our laboratory, and the results will be
published in due course.
To examine the hypothesis, we carried out the reaction of 7a,
which is syn- and anti-mixtures, using enantiomerically pure BINAP
(see Scheme 3). The high efficient kinetic resolution of 7a was
investigated in the presence of (S)-BINAP, [Rh(COD)Cl]2, and
AgSbF6 at 15 °C for 2 min. The corresponding cycloisomerization
product (2R,3S)-8a, which contained two of continual stereogenic
carbon centers, was obtained in 49% yield and over 99% ee, while
a mixture of (2R,5S)-7a (>99% ee) and (2S,5S)-7a (>99% ee) in
48% yields remained as the starting material. The other corre-
sponding enantiomer (2S,3R)-8a was formed with a mixture of
(2S,5R)-7a (>99% ee), and (2R,5R)-7a was obtained from the
reaction of 7a using (R)-BINAP as the ligand (see Scheme 4).8
To further clarify this reaction and obtain all of the enantio-
merically pure enantiomers of 7a, we prepared syn-(()-7a, and anti-
(()-7a, respectively.9 The reaction of syn-(()-7a in the presence
of 5 mol % (S)-BINAP, 2.5 mol % [Rh(COD)Cl]2 and 10 mol %
AgSbF6 at 15 °C for 2 min provided the desired cycloisomerization
product (2R,3S)-8a in 49% isolated yield and >99% ee along with
(2R,5S)-7a in 48% isolated yield and >99% ee. When the reaction
of syn-(()-7a was carried out using (R)-BINAP as the ligand, the
corresponding (2S 3R)-8a (>99% ee) and (2S,5R)-7a (>99% ee)
were obtained in 47% and 49% yield, respectively. With (S)-BINAP
as the ligand, the reaction of anti-(()-7a under the same condition
generates (2R,3S)-8a (>99% ee) in 48% isolated yield and (2S,5S)-
7a (>99% ee) in 49% yield. With (R)-BINAP as the ligand, the
reaction produced (2S,3R)-8a (>99% ee) and (2R,5R)-7a (>99%
ee) in 49% and 49% yield, respectively.10
Acknowledgment. This work was supported by NSF grant. We
thank Dr. A. Daniel Jones for his help in obtaining the mass spectral
data. We also thank the National Natural Science Foundation of
China.
Supporting Information Available: Spectroscopic data, GC, HPLC
spectra, and experimental details (PDF). This material is available free
References
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To understand the nature of the reaction, controlling reactions
were examined as shown in Scheme 5. When (S)-BINAP was used
Scheme 5
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Cao, P.; Zhang, X. Angew. Chem., Int. Ed. 2000, 39, 4104. (c) Lei, A.; He,
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(7) The trans configuration of cycloisomerization products was identified by
nOe experimentations of compounds 8a, and 8b.
(8) The absolute configurations of (2R,5S)-7a and (2S,5S)-7a were deduced
by the Mosher ester experimentation. Using (R)- and (S)-Mosher acids,
we prepared responding esters with enantiomerically pure compounds 7a.
(9) Bates, R. W.; Dfez-Martin, D.; Kerr, W. J.; Knight, J. G.; Ley, S. V.;
Sakellaridis, A. Tetrahedron 1990, 46, 4063.
(10) During the investigation of substrate scopes, substrates 3a and 3c were
successfully employed in the kinetic resolution protocol with (S)-BINAP.
Some others substrates S1, S3, S5 (in Supporting Information 2) were
examined, and the excellent selectivity was observed as expected. Please
see details in Supporting Information 2.
JA0351950
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J. AM. CHEM. SOC. VOL. 125, NO. 38, 2003 11473