Rules of stereoselectivity in tandem oxidative polycyclization reaction with rhenium(VII) oxides [4]

Full text of DOI:10.1021/ja981324e

9076
J. Am. Chem. Soc. 1998, 120, 9076-9077
Scheme 1. Oxidative Cyclization of 1 with CF3CO2ReO3
Rules of Stereoselectivity in Tandem Oxidative
Polycyclization Reaction with Rhenium(VII) Oxides
Santosh C. Sinha,†,‡ Ehud Keinan,†,‡ and Subhash C. Sinha*,†
Department of Molecular Biology and The Skaggs Institute
for Chemical Biology, The Scripps Research Institute
10550 North Torrey Pines Road, La Jolla, California 92037
Department of Chemistry, Technion-Israel Institute
of Technology, Technion City, Haifa 32000, Israel
Scheme 2. Stepwise Oxidative Polycyclization of 1a with
CF3CO2ReO3
a
ReceiVed April 17, 1998
The tandem oxidative polycyclization reaction with rhenium-
(VII) reagents, first reported in 1995,1 represents a powerful
methodology by which polyene alcohols can be converted into
poly-THF products with very high diastereoselectivity in a single
step.
a Prepared in situ from 1 equiv of Re2O7 and 1.2 equiv of TFAA.
Key: (a) CF3CO2ReO3 (2 equiv), TFAA (2.6 equiv), CH2Cl2, 2 h,
(Yield: 4a, 11%; 5a, 28%, recovered 1a, 37%); (b) CF3CO2ReO3 (1.5
equiv), TFAA (2 equiv), CH2Cl2, 6 h; (c) (S)-PhC(OMe)(CF3)COCl,
DMAP, CH2Cl2; (d) (R)-PhC(OMe)(CF3)COCl, DMAP, CH2Cl2.
Kennedy’s pioneering work on the monocyclization reaction
with simple bis-homoallylic alcohols has suggested that the
stereochemical outcome of this reaction leads consistently to trans-
THF products.2 We have confirmed this general rule in our early
studies with mono- and also with a few bis-cyclization reactions,1,3
and similar results were also reported by McDonald.4 Therefore,
we were surprised to observe the exclusive formation of 2a, rather
than its expected isomer 3a, in the triple oxidative cyclization
reaction with 1a and trifluoroacetylperrhenate (CF3CO2ReO3)
(Scheme 1).5 What we discovered was inconsistent with the
findings of an independent study by McDonald who reported that
the reaction of very similar trienol substrates, 1b and 1c, with
the same oxidant, CF3CO2ReO3, afforded the all-trans products,
3b and 3c, respectively.6
Scheme 3. Synthesis of 2c and 3c from L-(+)-diethyl tartratea
a Key: (a) i. TsOH, MeOH-H2O, rt, 16 h. ii. MsCl, Et3N, CH2Cl2, 0
°C, 2 h. (b) i. AD-mix-â, MeSO2NH2, tert-BuOH-H2O, 18 h. ii. Pyridine,
reflux, 2 h. (c) i. AD-mix-R, MeSO2NH2, tert-BuOH-H2O, 18 h. ii.
Pyridine, reflux, 2 h.
Considering the immense synthetic importance of the tandem
oxidative polycyclization reaction, we felt that the discrepancy
between ours and McDonald’s results had to be resolved. More
importantly, to allow the use of this reaction in a stereochemically
predictable way, one must understand the stereochemical relation-
ship between the polyenol substrate and the poly-THF product.
Here, on the basis of a systematic study, we confirm that the
polycyclization of 1 with CF3CO2ReO3 produces 2 and not 3.
Moreover, we propose a set of rules for predicting the stereo-
chemistry of the poly-THF products obtained by tandem oxidative
cyclization reaction with CF3CO2ReO3.7
The relative and absolute stereochemistries of the triple
cyclization product 2a were elucidated by carrying out the reaction
in a stepwise manner (Scheme 2). Partial oxidative cyclization
of 1a with CF3CO2ReO3 afforded a mixture of the mono- and
bis-THF products, 4a and 5a, along with recovered starting
material. The reaction of the mixture of 4a and 5a with an
additional amount of CF3CO2ReO3 afforded 2a. The stereochem-
istry of the free hydroxyl group in 2a, 4a, and 5a was determined
on the basis of 19F NMR spectral data of their (R) and (S)
Mosher’s esters (see Supporting Information).8 The structure of
2a was further corroborated by 2D 1H-1H COSY, TOCSY, and
ROESY experiments with the bis-benzoate ester of 2a. Finally,
we prepared both compounds 2a9 and 3a10 by independent
asymmetric synthesis. These experiments confirmed unequivo-
cally that the tris-THF product obtained by the tandem oxidative
cyclization of 1a is 2a and not 3a.
Compound 2b was easily prepared from 2a Via a three-step
sequence, desilation to produce corresponding diol, selective
monotosylation of the primary alcohol, and LAH reductive
cleavage of the tosylate function. Compounds 2c and 3c were
prepared from the enantiomerically pure acetonide 6 (Scheme 3)
which was synthesized from L-(+)-diethyl tartrate (see Supporting
Information). Comparison of the spectral properties of our
compounds, 2b, 2c, and 3c, with the original spectra kindly
provided by McDonald revealed that the correct structures of
compounds 49 and 48 described in ref 6 are also 2b and 2c,
respectively, and not 3b and 3c as reported.
* To whom the correspondence should be addressed. Phone: (619) 784-
8512. Fax: (619) 784-8732. E-mail: subhash@scripps.edu.
† The Scripps Research Institute.
‡ Technion-Israel Institute of Technology.
The above-described observation that trans,trans,trans-trienols
1a-c underwent stereoselective triple cyclization to give a trans,-
cis,cis-tris-THF product was quite intriguing considering our
previously reported observations with a cis,cis-(4,8)-dienol sub-
strate that afforded trans,trans-bis-THF product.1 Apparently, the
relative configuration of the resultant THF rings strongly depends
on the configuration of the vicinal oxygen functions formed in
(1) Sinha, S. C.; Sinha-Bagchi, A.; Keinan, E. J. Am. Chem. Soc. 1995,
117, 1447.
(2) (a) Tang, S.; Kennedy, R. M. Tetrahedron Lett. 1992, 33, 3729. (b)
Tang, S.; Kennedy, R. M. Tetrahedron Lett. 1992, 33, 5299. (c) Tang, S.;
Kennedy, R. M. Tetrahedron Lett. 1992, 33, 5303. (d) Boyce, R. S.; Kennedy,
R. M. Tetrahedron Lett. 1994, 35, 5133.
(3) (a) Sinha, S. C.; Sinha-Bagchi, A.; Yazbak, A.; Keinan, E. Tetrahedron
Lett. 1995, 36, 9257. (b) Sinha, S. C.; Sinha, A.; Yazbak, A.; Keinan, E. J.
Org. Chem. 1996, 61, 7640. (c) Keinan, E.; Sinha, A.; Yazbak, A.; Sinha, S.
C.; Sinha, S. C. Pure Appl. Chem. 1997, 69, 423.
(4) McDonald, F. E.; Towne, T. B. J. Org. Chem. 1995, 60, 5750.
(5) Sinha, S. C.; Sinha, A.; Sinha, S. C.; Keinan, E. J. Am. Chem. Soc.
1997, 119, 12014.
(6) Towne, B. T.; McDonald, F. E. J. Am. Chem. Soc. 1997, 119, 6022.
(7) In contrast to other rhenium(VII) oxidants, polycyclization with
trifluoroacetylperrhenate was found to proceed with high stereoselectivity and
high yields, particularly with acid-sensitive substrates (ref 6). Therefore, this
study was carried out with trifluoroacetylperrhenate.
(8) (a) Sullivan, G. R.; Dale, J. A.; Mosher, H. S. J. Org. Chem. 1973, 38,
2143. (b) Ohtani, I.; Kusumi, T.; Kashman, Y.; Kakisawa, H. J. Am. Chem.
Soc. 1991, 113, 4092. (c) Rieser, M. J.; Hui, Y.-H.; Rupprecht, J. K.;
Kozlowski, J. F.; Wood, K. V.; McLaughlin, J. L.; Hanson, P. R.; Zhuang,
Z.; Hoye, T. R. J. Am. Chem. Soc. 1992, 114, 10203.
(9) For an asymmetric synthesis of 2a, see: ref 5 (Supporting Information).
(10) . For an asymmetric synthesis of 3a see: Sinha, S. C.; Sinha, A.;
Sinha, S. C.; Keinan, E. J. Am. Chem. Soc. 1998, 120, 4017.
S0002-7863(98)01324-9 CCC: $15.00 © 1998 American Chemical Society
Published on Web 08/20/1998

Communications to the Editor
J. Am. Chem. Soc., Vol. 120, No. 35, 1998 9077
Scheme 4. Tandem Oxidative Cyclization Reactions with
CF3CO2ReO3
Scheme 6. Plausible Transition States for Oxidative
Cyclization with Re(VII) considering a 3 + 2 Addition
Mechanisma
a
a Key: Rd(CH2)2OBPS (a) CF3CO2ReO3 (2.5 equiv) and TFAA (3
equiv), CH2Cl2, 6 h.
a The other ligands on Re are omitted for clarity.
Scheme 5. Synthesis of 15a
a Key: (a) i. CF3CO2ReO3, lutidine, CH2Cl2, 18 h. ii. MsCl, Et3N,
CH2Cl2, 0 °C, 2 h. (b) AD-mix-R, MeSO2NH2, tert-BuOH-H2O, 18 h.
(c) Pyridine, reflux, 2 h. (d) i. p-Nitrobenzoic acid, DEAD, PPh3, C6H6,
3 h, ii. LiOH, THF-H2O (1:1), 60 °C, 3 h.
Figure 1.
previous cyclizations, which arises from the geometry of the
double bonds in the polyenol substrate.
a potential coordination site, the substrate may become a bidentate
ligand to rhenium. In that case, a pseudoaxial position would be
energetically preferred in the transition state (II), leading to a
cis-THF ring. Nevertheless, the coordinating efficiency of this
bidentate ligand depends on the relative configuration of the two
oxygen functions. With a threo relative configuration the reaction
proceeds via a sterically favored exo-type transition state, II-T.
By contrast, the erythro configuration requires a sterically
disfavored endo-type transition state, II-E, rendering the non-
chelated structure, I, energetically more favorable.
Another observation of cis-THF rings in the tandem oxidative
cyclization reaction with Re(VII) has been recently reported by
Morimoto and Iwai who studied highly substituted systems
(tertiary alcohols and trisubstituted double bonds).12 Their results
are consistent with our model. (1.) As observed in our less
substituted substrates, the first cyclization produces predominantly
a trans-THF ring. (2.) The second cyclization produces pre-
dominantly a cis-THF ring. This may be expected for tertiary
alcohols because, for substrates having an alkyl group instead of
H1, there is no steric advantage of I over II. Yet, when
coordination to Re becomes highly sterically demanding, e.g. with
the erythro substrate 8 in ref 1, the transition state is II-E (having
a methyl group instead of H1 and H2 and R′′ ) iPr) which results
in rather low cis selectivity (2:1).
To further understand the stereochemical rules of this reaction,
we have prepared four dienol substrates 8-11 (see Supporting
Information) and subjected them to the tandem oxidative biscy-
clization reaction with trifluoroacetyl perrhenate (CF3CO2ReO3),
which yielded the only isolatable products 12-15 (Scheme 4) in
40-48% yields. We used both NMR spectroscopy and inde-
pendent asymmetric synthesis to determine the stereochemistries
of the products. For example, the structures of compounds 12-
14 were determined on the basis of 2D 1H-1H COSY, TOCSY,
and ROESY of their bis-nitrobenzoate derivatives. We used 2D
1H-1H COSY and TOCSY to locate the signals of H-7 and H-10
which show an nOe correlation in the case of the bis-benzoate
esters of 12 and 13 and no such correlation in the case of 14.
This analysis clearly indicated that the B-ring is cis in 12 and 13
and is trans in 14. The structure of 15 was determined by an
independent synthesis starting with compound 8 (Scheme 5).
Compound 14 was converted to 15 in two steps (Scheme 5),
reinforcing our NMR structure determination of 14.
On the basis of the stereochemical relationships between 8-11
and 12-15 as well as our previously reported results, we propose
the following rules for the single step polycyclization of poly-
disubstituted alkenols with CF3CO2ReO3:
1. With simple bishomoallylic alcohol (where the hydroxyl
group is the only strong coordination site of rhenium), the first
THF ring is always produced with trans configuration.
2. If the two vicinal oxygen functions formed in the first
cyclization have a threo relationship, the next cyclization produces
a cis-THF ring.
3. If the vicinal oxygen functions formed in the first cyclization
have an erythro relationship, the next cyclization produces a trans-
THF ring.
In conclusion, we propose here a set of stereochemical rules
for the tandem oxidative cyclization reaction with CF3CO2ReO3.
Theoretical calculations that support these rules are underway.
Acknowledgment. We thank the U.S.-Israel Binational Science
Foundation, the Israel Cancer Research Fund, PharMore Biotechnologies,
and the Skaggs Institute for Chemical Biology for financial support. We
thank Prof. F. E. McDonald for copies of NMR spectra. E. K. is incumbent
of the Benno Gitter & Ilana Ben-Ami chair of Biotechnology, Technion.
The above rules reflect a dramatic change in the stereochemical
course of the tandem oxidative cyclization reaction when proceed-
ing from the first cyclization to the subsequent ones. A plausible
explanation for this phenomenon arises from the ability of the
newly formed THF ring to chelate the Re atom during the next
oxidative cyclization. As illustrated in Scheme 6 (top), in the
first cyclization step, the noncoordinating alkyl group has a high
preference to take a less sterically demanding pseudoequatorial
position in the proposed 3 + 2 transition state (I),11 leading to a
trans-THF ring. However, in cases where the group R possesses
Supporting Information Available: Synthetic scheme of compounds
6 and 8-11; 19F NMR spectral data of both Mosher’s esters of 2a, 4, 5
and two model compounds I and II; 1H and 13C NMR data of compounds
8-15, 1H and 2D 1H-1H NMR spectra of bis-nitrobenzoate derivatives
of 12-14 (15 pages, print/PDF). See any current masthead page for
ordering information and Web access instructions.
JA981324E
(11) Jorgensen, K. A.; Schiott, B. Chem. ReV. 1990, 90, 1483.
(12) Morimoto, Y.; Iwai, T. J. Am. Chem. Soc. 1998, 120, 1633.