Temporary silicon-tethered ring-closing metathesis approach to C2-symmetrical 1,4-diols: asymmetric synthesis of D-altritol

Full text of DOI:10.1021/jo9811524

6768
J . Org. Chem. 1998, 63, 6768-6769
Sch em e 1
Tem p or a r y Silicon -Teth er ed Rin g-Closin g
Meta th esis Ap p r oa ch to C2-Sym m etr ica l
1,4-Diols: Asym m etr ic Syn th esis of D-Altr itol
P. Andrew Evans* and V. Srinivasa Murthy
Brown Laboratory, Department of Chemistry and Biochemistry,
University of Delaware, Newark, Delaware 19716
Ta ble 1. Rin g-Closin g Meta th esis P r oced u r e for
Cou p lin g Op tica lly En r ich ed 1,4-Allylic Alcoh ols
Received J une 18, 1998
The enantioselective construction of the C2-symmetrical
molecules, particularly 1,4-diols, continues to attract sig-
nificant attention1 owing to their importance as precursors
to a variety of asymmetric catalysts,2 as chiral auxiliaries3
and as useful intermediates for two-directional synthesis.4
However, a survey of the literature revealed surprisingly
few methods for the preparation of this type of structural
motif, despite its significance as an important asymmetric
building block. The combination of temporary silicon-
tethering methodology5 with ring-closing metathesis6,7 has
been demonstrated, in an achiral system, to be a useful
method for the preparation of simple 1,4-diols.7a Herein, we
describe an adaptation of this concept, utilizing optically
enriched allylic alcohols 1 to facilitate the synthesis of
protected C2-symmetrical 1,4-diols 4, as outlined in Scheme
1.
Table 1 summarizes the results for the application of this
methodology to a series of optically enriched allylic alcohols.8
Treatment of the allylic alcohols 1a -e with diphenyldichlo-
rosilane and 2,6-lutidine furnished the bis-alkoxysilanes
(1) For a review on C2 symmetry in synthesis, see: Whitesell, J . K. Chem.
Rev. 1989, 89, 1581. For recent synthetic approaches to C2-symmetrical 1,4-
diols, see: (a) Lieser, J . K. Synth. Commun. 1983, 13, 765. (b) Seebach, D.;
Renaud, P. Helv. Chim. Acta 1985, 68, 2342. (c) Short, R. P.; Kennedy, R.
M.; Masamune, S. J . Org. Chem. 1989, 54, 1755. (d) Kim, M.-J .; Lee, I. S.
Synlett 1993, 767. (e) Zwaagstra, M. E.; Meetsma, A.; Feringa, B. L.
Tetrahedron: Asymmetry 1993, 4, 2163. (f) Morin, C. Tetrahedron Lett. 1993,
34, 5095. (g) Vettel, S.; Knochel, P. Tetrahedron Lett. 1994, 35, 5849 and
pertinent references therein.
(2) (a) Burk, M. J . J . Am. Chem. Soc. 1991, 113, 8518. (b) Burk, M. J .;
Feaster, J . E.; Harlow, R. L. Tetrahedron: Asymmetry 1991, 2, 569 and
pertinent references therein.
(3) Chong, J . M.; Clarke, I. S.; Koch, I.; Olbach, P. C.; Taylor, N. J .
Tetrahedron: Asymmetry 1995, 6, 409 and pertinent references therein.
(4) For a review on two-directional synthesis, see: Magnuson, S. R.
Tetrahedron 1995, 51, 2167.
(5) For recent reviews on temporary silicon-tethered strategies, see: (a)
Fensterbank, L.; Malacria, M.; Sieburth, S. McN. Synthesis 1997, 813. (b)
Gauthier, D. R., J r.; Zandi, K. S.; Shea, K. J . Tetrahedron 1998, 54, 2290.
(6) For recent reviews on ring-closing metathesis, see: (a) Grubbs, R.
H.; Miller, S. J .; Fu, G. C. Acc. Chem. Res. 1995, 28, 446. (b) Armstrong, S.
K. J . Chem. Soc., Perkin Trans. 1 1998, 371. (c) Grubbs, R. H.; Chang, S.
Tetrahedron 1998, 54, 4413.
(7) For some recent leading references on Ru-catalyzed ring-closing
metathesis, see: (a) Fu, G. C.; Grubbs, R. H. J . Am. Chem. Soc. 1992, 114,
5426. (b) Meng, D.; Su, D.-S.; Balog, A.; Bertinato, P.; Sorenson, E. J .;
Danishefsky, S. J .; Zheng, Y.-H.; Chou, T.-C.; He, L.; Horwitz, S. B. J . Am.
Chem. Soc. 1997, 119, 2733. (c) Martin, S. F.; Chen, H.-J .; Courtney, A. K.;
Liao, Y.; Patzel, M.; Ramser, M. N.; Wagman, A. A. Tetrahedron 1996, 52,
7251. (d) Furstner, A.; Langeman, K. J . Org. Chem. 1996, 61, 8746. (e)
Huwe, C. M.; Blechert, S. Synthesis 1997, 61. (f) Clark, J . S.; Kettle, J . G.
Tetrahedron Lett. 1997, 38, 127. (g) Barrett, A. G. M.; Baugh, S. P. D.;
Gibson, V. C.; Giles, M. R.; Marshall, E. L.; Procopiou, P. A. J . Chem. Soc.
Chem. Commun. 1997, 155. (h) Yang, Z.; He, Y.; Vourloumis, D.; Vallberg,
H.; Nicolaou, K. C. Angew. Chem., Int. Ed. Engl. 1997, 36, 166. (i) Kim, S.
H.; Figueroa, I.; Fuchs, P. Tetrahedron Lett. 1997, 38, 2601. (j) Harrity, J .
P. A.; Visser, M. S.; Gleason, J . D.; Hoveyda, A. H. J . Am. Chem. Soc. 1997,
119, 1488. (k) Litinas, K. E.; Salteris, B. E. J . Chem. Soc., Perkin Trans. 1
1997, 2869. (l) Delgado, M.; Martin, J . D. Tetrahedron Lett. 1997, 38, 6299.
(m) Linderman, R. J .; Siedlecki, J .; O’Neill, S. A.; Sun, H. J . Am. Chem.
Soc. 1997, 119, 6919. (n) Kirkland, T. A.; Grubbs, R. H. J . Org. Chem. 1997,
62, 7310. (o) Crimmins, M. T.; Choy, A. L. J . Org. Chem. 1997, 62, 7548.
(p) Ovaa, H.; Leeuwenburgh, M. A.; Overkleeft, H. S.; Van der Marel, G.
A.; Van Boom, J . H. Tetrahedron Lett. 1998, 39, 3025. (q) Miller, J . F.;
Termin, A.; Koch, K.; Piscopio, A. D. J . Org. Chem. 1998, 63, 3158. (r) Burke,
S. D.; Ng, R. A.; Morrison, J . A.; Alberti, M. J . J . Org. Chem. 1998, 63,
3160 and pertinent references cited within these articles.
a
All the reactions were carried out on a 1.0 mmol reaction
scale.12 Isolated yields. c The ring-closing metathesis reactions
were carried out on a 0.25 mmol reaction scale at a concentration
of 0.05 M in refluxing dichloromethane.14
b
2a -e in excellent yield (entries 1-5). Preliminary studies
established the optimum conditions for the ring-closing
metathesis reaction, in terms of the catalyst loading, type
of solvent, and concentration. These studies determined that
an initial catalyst loading of 8 mol % followed by an
additional 2.5 mol % after approximately 20 h, at a concen-
tration of 0.05 M in refluxing dichloromethane, were re-
quired for the smooth formation of the diphenyl silaketals
4a -e. Interestingly, despite the somewhat extended reac-
tion times and elevated temperatures,11 the process appears
to be fairly general as illustrated by the alkyl and aryl
examples listed in Table 1 (entries 1-5).
The diphenyl silaketals 4 represent protected C2-sym-
metrical 1,4-diols that can be readily elaborated into a
(8) The enantiomerically enriched allylic alcohols 1 were all prepared in
the following manner. Sharpless asymmetric epoxidation9 of the primary
allylic alcohol i followed by the activation and rearrangement of the 2,3-
epoxy alcohol ii furnished the allylic alcohol 1 in excellent overall yield.10
(9) Gao, Y.; Hanson, R. M.; Klunder, J . M.; Ko, S. Y.; Masamune, H.;
Sharpless, K. B. J . Am. Chem. Soc. 1987, 109, 5765.
(10) Habashita, H.; Kawasaki, T.; Akaji, M.; Tamamura, H.; Kimachi,
T.; Fujii, N.; Ibuka, T. Tetrahedron Lett. 1997, 38, 8307.
(11) The reduced rates of reaction are presumably a function of the
increased steric hindrance due to allylic substituent. For related examples
of this type of problem in ring-closing metathesis, see: (a) Chang, S.; Grubbs,
R. H. Tetrahedron Lett. 1997, 38, 4757. (b) Meyer, C.; Cossy, J . Tetrahedron
Lett. 1997, 38, 7861.
S0022-3263(98)01152-9 CCC: $15.00 © 1998 American Chemical Society
Published on Web 09/12/1998

Communications
J . Org. Chem., Vol. 63, No. 20, 1998 6769
Sch em e 2
Sch em e 3
variety of intermediates.15 Scheme 2 represents an applica-
tion of this type of strategy in two-directional synthesis. The
allylic alcohol 5 was converted to the bis-alkoxysilane under
standard conditions and then treated with 50 mol % of 3 to
induce ring-closing metathesis,16 furnishing the bis-lactone
6 in 74% overall yield. This represents a particularly useful
synthetic intermediate that is currently being utilized for
the total synthesis of the potent antitumor annonaceous
acetogenin mucocin.17
(12) Gen er a l P r oced u r e for th e P r ep a r a tion of Bis-Alk oxysila n es
fr om Allylic Alcoh ols. The allylic alcohol 1a 13 (0.718 g, 2.2 mmol) was
dissolved in anhydrous dichloromethane (10 mL) and cooled with stirring
to 0 °C under nitrogen atmosphere. Diphenyldichlorosilane (0.21 mL, 1.02
mmol) was then added neat via syringe followed by 2,6-lutidine (0.47 mL,
4.04 mmol). The reaction mixture was allowed to warm to room temperature
and stirred for ca. 20 h. The reaction was then partitioned between
dichloromethane and water. The combined organic phases were dried
(Na2SO4), filtered, and concentrated in vacuo to afford a crude oil. Purifica-
tion by flash chromatography (eluting with 5% ethyl acetate in hexanes)
Scheme 3 illustrates another potentially powerful applica-
tion of this methodology applicable to the preparation of the
reduced carbohydrate D-altritol.18 Dihydroxylation of the
t
cyclic alkene 4a (TPS ) BuPh2Si) with a catalytic amount
of osmium tetraoxide in the presence of N-methylmorpholine
N-oxide, followed by treatment with tetra-N-butylammo-
nium fluoride, furnished D-altritol 8; this was then peracety-
lated to expedite isolation, affording the hexaacetate 7 in
75% overall yield.19 Treatment of 7 with a catalytic amount
of sodium methoxide in methanol furnished D-altritol 8 in
88% yield, identical in all respects to the reported data (1H
furnished the bis-alkoxy silane 2a (0.74 g, 87%) as a colorless syrup: [R]18
D
) -16.9 (c ) 1, CHCl3); IR (CHCl3) 3072 (s), 3012 (s), 2960 (s), 2932 (s),
2850 (s) 1590 (m) cm-1 1H NMR (400 MHz, CDCl3) δ 7.65-7.57 (m, 12H),
;
7.42-7.26 (m, 18H), 5.93 (ddd, J ) 17.1, 10.6, 6.0 Hz, 2H), 5.20 (dt, J )
17.1, 1.5 Hz, 2H), 5.09 (dt, J ) 10.4, 1.5 Hz, 2H), 4.46 (q, J ) 5.9 Hz, 2H),
3.68 (A of ABX, J AB ) 10.0, J AX ) 5.6 Hz, 2H), 3.52 (B of ABX, J AB ) 10.0,
J BX ) 6.2 Hz, 2H), 1.0 (s, 18H); 13C NMR (100 MHz, CDCl3) δ 138.02 (o),
135.61 (o), 135.53 (o), 135.21 (o), 133.55 (e), 133.14 (e), 130.05 (o), 129.48
(o), 127.57 (o), 115.81 (e), 74.65 (o), 67.89 (e), 26.77 (o), 19.20 (e); HRMS
(FAB) calcd for C52H60NaSi3O4 855.3697, found 855.3722.
and 13C NMR): [R]16 ) 3.1 (c ) 1.7, H2O) [lit.18 [R]20
)
D
D
3.2 (c ) 1.78, H2O)]. Hence, this represents a highly
strereoselective and expeditious method for the construction
of alditols.
(13) Mikiko, M.; Fumiaki, O.; Mayumi, M.; Yohko, T.; Yutaka, A.; Akihiro,
O. Chem. Pharm. Bull. 1997, 45, 962.
In conclusion, we have developed a temporary silicon-
tethered ring-closing metathesis protocol for the synthesis
of protected C2-symmetrical 1,4-diols. The advantage of this
type of approach is the ability to couple a wide range of
optically enriched allylic alcohols, which facilitates the
preparation of useful intermediates for target directed
synthesis. For example, the silaketal 4a was converted in
a highly stereoselective and expeditious manner to the
reduced carbohydrate D-altritol 8. It is anticipated that this
method should also be amenable to solid-phase synthesis and
thus allows for the preparation of carbohydrate libraries.
(14) Gen er a l P r oced u r e for th e Rin g-Closin g Meta th esis of th e Bis-
Alk oxysila n es. The diene 2b (0.214 g, 0.26 mmol) was dissolved in
anhydrous dichloromethane (5 mL) and the solution degassed in a sonication
bath. Grubbs’ catalyst 3 (0.016 g, 0.02 mmol) was added and the mixture
heated at reflux for ca. 20 h. An additional amount of 3 (0.005 g, 2.5 mol %)
was then added and the reaction mixture heated at reflux for a further ca.
6 h (NMR analysis). The reaction mixture was then cooled to ambient
temperature and concentrated in vacuo to afford the crude product.
Purification by flash chromatography (eluting with 20% benzene in hexanes)
furnished the cyclic bis-alkoxysilane 4a (0.189 g, 91%) as a white crystalline
solid: mp 115-118 °C.; [R]18 ) -2.4 (c ) 1, CHCl3); IR (CHCl3) 3072 (s),
D
2991 (s), 2960 (s), 2859 (s) 1591 (w) cm-1
;
1H NMR (400 MHz, CDCl3) δ
7.73-7.67 (m, 12H), 7.46-7.30 (m, 18H), 5.78 (s, 2H), 4.88 (t, J ) 5.2, 2H),
3.84 (A of ABX, J AB ) 10.0, J AX ) 6.4 Hz, 2H), 3.73 (B of ABX, J AB ) 10.0,
J BX ) 5.6 Hz, 2H), 1.05 (s, 18H); 13C NMR (100 MHz, CDCl3) δ 135.62 (o),
134.84 (o), 133.61 (e), 133.50 (e), 131.20 (o), 130.40 (o), 129.59 (o), 127.82
(o), 127.63 (o), 71.80 (o), 67.87 (e), 26.78 (o), 19.25 (e); HRMS (FAB) calcd
for C50H56NaSi3O4 827.3384, found 827.3369.
Ack n ow led gm en t. We thank Zeneca Pharmaceuticals
(Wilmington, DE) for generous financial support.
Su p p or tin g In for m a tion Ava ila ble: Full characterization
and proton spectra for compounds 1/2/4b-e and 5-9 (22 pages).
(15) The diphenyl silaketal 4a was converted to the C2-symmetrical 1,4-
diol 9, which is a common intermediate for the preparation of the trans-
2,5-diphenylpyrrolidine chiral auxiliary.3 Reduction of the cis-alkene 4b with
Raney Ni followed by the desilylation with tetra-N-butylammonium fluoride
furnished the C2-symmetrical 1,4-diol 9 in 65% overall yield.
J O9811524
(17) Shi, G.; Alfonso, D.; Fatope, M. O.; Zeng, L.; Gu, Z.-m.; Zhao, G.-x.;
He, K.; MacDougal, J . M.; McLaughlin, J . L. J . Am. Chem. Soc. 1995, 117,
10409.
(18) (a) Hann, R. M.; Haskins, W. T.; Hudson, C. S. J . Am. Chem. Soc.
1947, 69, 624. (b) Angyal, S. J .; Le Fur, R. Carbohydr. Res. 1980, 84, 201.
(c) Ko, S. Y.; Lee, A. W. M.; Masamune, S.; Reed, L. A., III; Sharpless, K.
B.; Walker, F. J . Tetrahedron 1990, 46, 245.
(16) This proved to be a more challenging example that required 0.5 equiv
of the Grubbs’ catalyst 3 for complete conversion.
(19) D-Altritol hexaacetate: [R]14D ) 39 (c ) 0.6, CHCl3) [lit.18 for L-altritol
hexaacetate, [R]20 ) -38.7 (c ) 0.59, CHCl3)].
D