Tandem Glycolate Claisen Rearrangement/Ring-Closing Metathesis: A Stereochemically General Synthesis of Substituted Dihydropyran-2-carboxylates

Full text of DOI:10.1021/jo980163u

3
160
J . Org. Chem. 1998, 63, 3160-3161
Ta n d em Glycola te Cla isen Rea r r a n gem en t/
Rin g-Closin g Meta th esis: A Ster eoch em ica lly
Gen er a l Syn th esis of Su bstitu ted
Sch em e 1
Dih yd r op yr a n -2-ca r boxyla tes
Steven D. Burke,* Raymond A. Ng,
J ames A. Morrison, and Michael J . Alberti
Department of Chemistry, University of WisconsinsMadison,
Madison, Wisconsin 53706-1396
Received February 2, 1998
Hydropyrans are important structural units found in
synthetic and natural ionophores and polyether mac-
rolides.1 Recent efforts directed at hydropyran synthesis
,2
3
4
include anionic cyclization, cationic cyclization, radical
cyclization,5 hetero-Diels-Alder cycloaddition, dioxanone
6
7
Claisen rearrangement, and ring-closing metathesis of enol
ethers.8 To date, however, there has been no demonstration
of a stereochemically general method for the synthesis of
dihydropyrans of general structure 1 (eq 1).
(
1) (a) Burke, S. D.; Porter, W. J .; Rancourt, J .; Kaltenbach, R. F.
Tetrahedron Lett. 1990, 31, 5285. (b) Burke, S. D.; O’Donnell, C. J .; Porter,
W. J .; Song, Y. J . Am. Chem. Soc. 1995, 117, 12649. (c) Burke, S. D.;
O’Donnell, C. J .; Hans, J . J .; Moon, C. W.; Ng, R. A.; Adkins, T. W.; Packard,
G. K. Tetrahedron Lett. 1997, 38, 2593.
(2) (a) Polyether Antibiotics; Westley, J . W., Ed.; Marcel Dekker: New
York, 1983; Vols. I and II. (b) Dobler, M. Ionophores and Their Structures;
Wiley-Interscience: New York, 1981. (c) Robinson, J . A. Prog. Chem. Org.
Nat. Prod. 1991, 58, 1-81.
(
3) (a) Mart ´ı n, V. S.; Nu n˜ ez, M. T.; Ramirez, M. A.; Soler, M. A.
Tetrahedron Lett. 1990, 31, 763. (b) Mandai, T.; Ueda, M.; Kashiwagi, K.;
Kawada, M.; Tsuji, J . Tetrahedron Lett. 1993, 34, 111. (c) Burke, S. D.; J ung,
K. W.; Phillips, J . R.; Perri, R. E. Tetrahedron Lett. 1994, 35, 703. (d) Aicher,
T. D.; Kishi, Y. Tetrahedron Lett. 1987, 28, 3463. (e) Duan, J . J .-W.; Kishi,
Y. Tetrahedron Lett. 1993, 34, 7541. (f) Stamos, D. P.; Kishi, Y. Tetrahedron
Lett. 1996, 37, 8643. (g) Cooper, A. J .; Salomon, R. G. Tetrahedron Lett.
1
990, 31, 3813.
4) (a) Bartlett, P. A. In Asymmetric Synthesis; Morrison, J . D., Ed.;
(
Academic Press: New York, 1984; Vol. 3, p 411. (b) Boivin, T. L. B.
Tetrahedron 1987, 43, 3309. (c) Hashimoto, M.; Kan, T.; Yanagiya, M.;
Shirahama, H.; Matsumoto, T. Tetrahedron Lett. 1987, 28, 5665. (d) Faivre,
V.; Lila, C.; Saroli, A.; Doutheau, A. Tetrahedron 1989, 45, 7765. (e)
Nicolaou, K. C.; Prasad, C. V. C.; Somers, P. K.; Hwang, C.-K. J . Am. Chem.
Soc. 1989, 111, 5330. (f) Nicolaou, K. C.; Prasad, C. V. C.; Somers, P. K.;
Hwang, C.-K. J . Am. Chem. Soc. 1989, 111, 5335. (g) Semeyn, C.; Blaauw,
R. H.; Hiemstra, H.; Speckamp, W. N. J . Org. Chem. 1997, 62, 3426.
We envisioned the tandem sequence of glycolate Claisen
9
10
rearrangement /ring-closing metathesis as providing such
a protocol. Diene metathesis substrate 2 contains an
R-alkoxy-γ,δ-unsaturated ester, known to be available via
(
5) (a) Munt, S. P.; Thomas, E. J . J . Chem. Soc., Chem. Commun. 1989,
4
80. (b) Kim, S.; Fuchs, P. L. J . Am. Chem. Soc. 1991, 113, 9864. (c) Burke,
S. D.; Rancourt, J . J . Am. Chem. Soc. 1991, 113, 2335. (d) Esch, P. M.;
Hiemstra, H.; de Boer, R. F.; Speckamp, W. N. Tetrahedron 1992, 48, 4659.
9
a glycolate Claisen rearrangement of substrates such as 3.
(
6) (a) Danishefsky, S. J .; DeNinno, M. P. Angew. Chem., Int. Ed. Engl.
1
987, 26, 15. (b) Danishefsky, S. J .; Selnick, H. G.; Zelle, R. E.; DeNinno,
Merger of two allylic alcohol subunits with a bromoacetic
acid linchpin would afford this glycolate Claisen substrate.
Stereogenicity at the indicated centers in 1 would follow in
a predictable fashion from the indicated stereogenic centers
in the allylic alcohol components 4 and 5. This convergent
and stereochemically general synthesis of substituted hy-
dropyrans is illustrated herein for cis- and trans-3-substi-
tuted dihydropyran-2-carboxylates and for all four diaster-
eomeric permutations of 3,6-disubstituted dihydropyran-2-
carboxylates.
M. P. J . Am. Chem. Soc. 1988, 110, 4368. (c) Lubineau, A.; Aug e´ , J .; Lubin,
N. Tetrahedron 1993, 49, 4639.
(
7) (a) Burke, S. D.; Armistead, D. M.; Schoenen, F. J . J . Org. Chem.
984, 49, 4320. (b) Burke, S. D.; Armistead, D. M.; Schoenen, F. J .; Fevig,
J . M. Tetrahedron 1986, 42, 2787.
8) Nicolaou, K. C.; Postema, M. H. D.; Claiborne, C. F. J . Am. Chem.
Soc. 1996, 118, 1565.
9) (a) Burke, S. D.; Fobare, W. F.; Pacofsky, G. J . J . Org. Chem. 1983,
8, 5221. (b) Bartlett, P. A.; Barstow, J . F. Tetrahedron Lett. 1982, 23, 623.
c) Bartlett, P. A.; Tanzella, D. J .; Barstow, J . F. Tetrahedron Lett. 1982,
3, 619. (d) Ager, D. J .; Cookson, R. C. Tetrahedron Lett. 1982, 23, 3419.
e) Sato, T.; Tajima, K.; Fujisawa, T. Tetrahedron Lett. 1983, 24, 729. (f)
1
(
(
4
(
2
(
Kallmerten, J .; Gould, T. J . Tetrahedron Lett. 1983, 24, 5177. (g) Fujisawa,
T.; Tajima, K.; Sato, T. Chem. Lett. 1984, 1669. (h) Sato, T.; Tsunekawa,
H.; Kohama, H.; Fujisawa, T. Chem. Lett. 1986, 1553. (i) Barrish, J . C.;
Lee, H. L.; Baggiolini, E. G.; Uskokovic, M. R. J . Org. Chem. 1987, 52, 1372.
A simple example in a racemic series is illustrated in
Scheme 1. O-Alkylation of allyl alcohol with bromoacetic
acid (2 equiv of NaH, THF, 66 °C) gave 6, which afforded
(
6
1
j) Ireland, R. E.; Wipf, P.; Armstrong, J . D., III. J . Org. Chem. 1991, 56,
50. (k) Ireland, R. E.; Meissner, R. S.; Rizzacasa, M. A. J . Am. Chem. Soc.
993, 115, 7166. (l) Hattori, K.; Yamamoto, H. Tetrahedron 1994, 50, 3099.
11
glycolate Claisen substrate 7 upon Steglich-Hassner
coupling with (E)-3-penten-2-ol. Subjection of the ester to
standard Ireland-Claisen conditions effected the [3,3]-
(
10) (a) Grubbs, R. H.; Miller, S. J .; Fu, G. C. Acc. Chem. Res. 1995, 28,
12
4
2
46. (b) Schuster, M.; Blechert, S. Angew. Chem., Int. Ed. Engl. 1997, 36,
036.
(
11) (a) Neises, B.; Steglich, W. Angew. Chem., Int. Ed. Engl. 1978, 17,
22. (b) Hassner, A.; Alexanian, V. Tetrahedron Lett. 1978, 4475.
12) (a) Ireland, R. E.; Mueller, R. H. J . Am. Chem. Soc. 1972, 94, 5897.
b) Ireland, R. E.; Willard, A. K. Tetrahedron Lett. 1975, 3975. (c) Ireland,
(13) (a) see ref 9a. (b) Typical procedure: A solution of glycolate ester in
THF is added slowly to a solution of freshly prepared LDA at -100 °C.
After the solution is stirred at -100 °C for 15 min, the supernatant of a
centrifuged 1:1 (v/v) mixture of TMSCl and triethylamine is added. The
mixture is allowed to warm to ambient temperature and stirred overnight.
The silyl ester is hydrolyzed by treatment with either 1 M NaOH or 1 M
HCl. The acid is isolated by acid/base extractions.
5
(
(
R. E.; Mueller, R. H.; Willard, A. K. J . Am. Chem. Soc. 1976, 98, 2868. For
recent reviews, see: (d) Blechert, S. Synthesis 1989, 71. (e) Ziegler, F. E.
Chem. Rev. 1988, 88, 1423.
S0022-3263(98)00163-7 CCC: $15.00 © 1998 American Chemical Society
Published on Web 04/16/1998

Communications
J . Org. Chem., Vol. 63, No. 10, 1998 3161
Ta ble 1. Ta n d em Glycola te Cla isen Rea r r a n gem en t/
Rin g-Closin g Meta th esis
the substrate allylic stereocenter (*) via equatorial deploy-
ment of the methyl substituent on the pericyclic chairlike
transition structure (see Scheme 1). Although good Claisen
rearrangement diastereoselectivities were observed in en-
tries 1-3 using standard conditions for silyl ketene acetal
formation,12 the more oxygenated substrates in entries 4-7
gave poor diastereoselectivities (∼1:1) and substantial
amounts of C-silylation byproducts with this protocol.
Fortunately, adding 2 equiv of LDA to a solution of ester
and TMSCl in 20% (v/v) HMPA/THF at -100 °C for 1 h and
then warming to ambient temperature9k afforded moderate
to high (4:1 to >20:1) stereoselectivities and better rear-
rangement yields. The major isomer in each case was
separated by flash chromatography for use as the substrate
for the next step.
Table 1 also summarizes the ring-closing metathesis
reactions of the glycolate Claisen rearrangement products.
The substrates in entries 1-3 generally reacted under
milder conditions (CH2Cl2, 23 °C, 1-3 h or benzene, 80 °C,
1
h) than those in entries 4-7. The latter substrates have
allylic branching at both alkene termini, which is known to
retard the metathesis reaction.17 Reaction times of several
days at 23 °C in CH2Cl2 were required for entries 4-7 to
provide moderate to good yields of the 2,3,6-trisubstituted
dihydropyrans 25-28. Conducting the reactions at higher
concentrations, in CHCl3, or in the presence of cuprous
chloride1 failed to promote acceleration.
4c
The product 25 of entry 4 matches the absolute stereo-
chemistry of the four asymmetric carbons in the hydropyran
subunit of the ionophore antibiotic zincophorin.1 The entry
8
5
product 26 possesses the relative (but enantiomeric)
stereochemistry present in the ionophore antibiotic indano-
mycin.19 Dihydropyran-2-carboxylate products 25 and 26
were stereochemically correlated with known samples pre-
pared by alternate methods. The relative ease by which
enantiopure allylic alcohols can now be obtained2 allows for
their employment in this glycolate Claisen/ring-closing me-
tathesis tandem sequence. Products 25-28 represent all
four possible diastereomeric 2,3,6-trisubstituted dihydropy-
rans (trans, trans; cis, trans; trans, cis; cis, cis), thus
demonstrating a stereochemically universal route to these
heterocycles.21
0
a
Diastereomeric ratio; isomers separated by flash chromatog-
b
raphy. RCM conditions: PhH (0.01 M), 60-80 °C, 1-3 h, 5 mol
c
%
2
of 9. RCM conditions: CH2Cl2 (0.1 M), 23-60 °C, 4-5 days,
0 mol % of 9.
sigmatropic shift via the bracketed silyl ketene acetal.13
Chelation control over enolate geometry and π-facial prefer-
ences dictated by the chairlike transition state produce, after
esterification, the metathesis substrate 8b with the relative
stereochemistry shown for the major isomer (diastereose-
lectivity 6:1). Exposure of 8b to [RuCl2(dCHPh)(PCy3)2]
Ack n ow led gm en t. Support of this work by the Na-
tional Institutes of Health (GM 28321, CA 74394) is
gratefully acknowledged. Use of high-field NMR spectrom-
eters was made possible by the support of the NIH (ISIO
RRO 8389-01) and the NSF (CHE-9208463).
1
4
(
9) in benzene (60 °C, 0.5 h) or CH2Cl2, (23 °C, 3 h) gave
cis-3-substituted dihydropyran-2-carboxylate 10 in 73%
yield.
Further examples of metathesis substrate preparation via
the glycolate Claisen rearrangement are summarized in
Table 1. Combination of two enantiopure alcohols
bromoacetic acid to provide glycolate Claisen substrate 3
as in Scheme 1) is represented in entries 4-7. Control of
the relative stereochemistry at the nascent C2 and C3
centers (cf. Table 1, entries 4 and 5) is exerted by the choice
of Z- or E-allylic alcohols in substrate ester syntheses.
Absolute stereogenicity at those centers is transferred from
Su p p or tin g In for m a tion Ava ila ble: Experimental proce-
dures and characterization data (79 pages).
J O980163U
1
5,16
with
(
17) (a) F u¨ rstner, A.; Langemann, K. J . Org. Chem. 1996, 61, 3942. (b)
F u¨ rstner, A.; Langemann, K. Synthesis 1997, 792.
18) (a) Gr a¨ fe, U.; Schade, W.; Roth, M.; Radics, L.; Incze, M.; Ujsz a´ szy,
(
(
K. J . Antibiot. 1984, 37, 836. (b) Brooks, H. A.; Gardner, D.; Poyser, J . P.;
King, T. J . J . Antibiot. 1984, 37, 1501.
(19) Westley, J . W.; Evans, R. H., J r.; Liu, C.-M.; Hermann, T.; Blount,
J . F. J . Am. Chem. Soc. 1978, 100, 6784.
(20) (a) Gao, Y.; Hanson, R. M.; Klunder, J . M.; Ko, S. Y.; Masamune,
H.; Sharpless, K. B. J . Am. Chem. Soc. 1987, 109, 5765. (b) Corey, E. J .;
Bakshi, R. K.; Shibata, S. J . Am. Chem. Soc. 1987, 109, 5551. (c) Corey, E.
J .; Bakshi, R. K.; Shibata, S.; Chen, C.-P.; Singh, V. K. J . Am. Chem. Soc.
1987, 109, 7925. (d) Midland, M. M.; McDowell, D. C.; Hatch, R. L.;
Tramontano, A. J . Am. Chem. Soc. 1980, 102, 867. (e) Midland, M. M.;
Tramontano, A.; Kazubski, A.; Graham, R. S.; Tsai, D. J . S.; Cardin, D. B.
Tetrahedron 1984, 40, 1371.
(21) (a) This work has been reported in part. See: Ng, R. A.; Morrison,
J . A.; Burke, S. D. Abstracts of the 213th National Meeting of the American
Chemical Society, April 13-17, 1997, San Francisco, CA; American Chemical
Society: Washington, DC, 1997; Abstract #ORGN 431. (b) For related
independent work, see: Miller, J . F.; Termin, A.; Koch, K.; Piscopio, A. D.
J . Org. Chem. 1998, 63, 3158-3159.
(
14) (a) Fu, G. C.; Nguyen, S. T.; Grubbs, R. H. J . Am. Chem. Soc. 1993,
1
15, 9856. (b) Schwab, P.; France, M. B.; Ziller, J . W.; Grubbs, R. H. Angew.
Chem., Int. Ed. Engl. 1995, 34, 2039. (c) Dias, E. L.; Nguyen, S. T.; Grubbs,
R. H. J . Am. Chem. Soc. 1997, 119, 3887.
(15) (3S,4R)- and (3R,4R)-4-Methyl-5-(phenylmethoxy)-1-penten-3-ol (used
in entries 4-7) were prepared from (S)-(+)-methyl 3-hydroxy-2-methylpro-
pionate. See: Burke, S. D.; Piscopio, A. D.; Marron, B. E.; Matulenko, M.
A.; Pan, G. Tetrahedron Lett. 1991, 32, 857.
(
16) (S)-(Z)- and (S)-(E)-3-penten-2-ol (used in entries 4-7) were prepared
from (S)-ethyl lactate by the method of Kurth: (a) McKew, J . C.; Kurth, M.
J . Org. Prep. Proced. Int. 1993, 25, 125. (b) McKew, J . C.; Kurth, M. J . J .
Org. Chem. 1993, 58, 4589.