Regio- and stereocontrolled 6-endo-trig radical cyclization of vinyl radicals: A novel entry to carbasugars from carbohydrates

Full text of DOI:10.1021/jo981989z

9
626
J . Org. Chem. 1998, 63, 9626-9627
Regio- a n d Ster eocon tr olled 6-En d o-Tr ig
Ra d ica l Cycliza tion of Vin yl Ra d ica ls: A
Novel En tr y to Ca r ba su ga r s fr om
Ca r boh yd r a tes
Sch em e 1
Ana M. G o´ mez,* Gerardo O. Danel o´ n,
Seraf ´ı n Valverde, and J . Crist o´ bal L o´ pez*
Instituto de Qu ´ı mica Org a´ nica General (CSIC),
J uan de la Cierva 3, 28006 Madrid, Spain
Received October 1, 1998
The term “carbasugar” is currently used to describe
monosaccharide analogues having a methylene group in-
1
stead of the ring oxygen atom. Carbasugars have received
considerable attention recently due to their close structural
resemblance to carbohydrates and to the interesting range
of biological activities which they have shown. This interest
has resulted in the development of a plethora of synthetic
methods, and all 16 racemic carbapyranoses and most of the
exo)-endo-trig11 radical cyclization of an intermediate vinyl
2
radical (2), generated by tri-n-butyltin hydride (Bu SnH)
3
addition to a carbohydrate enyne 1, to produce a cyclohex-
enyl radical, 3, that after hydrogen transfer will lead to 4.
Standard manipulations on alkenyl stannane 4 will then
pave the way to carbasugar 5.
The synthetic pathway (Scheme 2) started with com-
mercially available D-glucose or D-galactose pentaacetates
3
2 enantiopure carbapyranoses have already been pre-
3
,4
pared. There are, however, only two reports involving a
5
radical cyclization as the key step in the formation of the
carbasugar cyclohexane ring.6,7 Both methods utilize a 6-exo
(6a and 6b, respectively) which were transformed in four
radical cyclization although they differ on the nature of the
6
7
steps into 2,3:4,6-di-O-isopropylidene-D-gluco and D-galacto
unsaturated radical acceptor (6-exo-trig and 6-exo-dig ). As
part of an ongoing program in our laboratory aimed at the
synthesis of carbocycles from carbohydrates,8 we report in
this paper on a novel entry to carbasugars from monosac-
charides which features the radical cyclization of a vinyl
radical10 as the key step. We have successfully applied this
method for the preparation of carbasugar analogues of
D-glucose and D-galactose.
pyranoses (7a and 7b, respectively).1
2,13
Known alkynes 8a ,b
,9
Sch em e 2
Our approach for the synthesis of carbasugars from mono-
saccharides is illustrated in Scheme 1. It involves the 6-(π-
(
(
1) Suami, T.; Ogawa, S. Adv. Carbohydr. Chem. Biochem. 1990, 48, 21.
2) (a) Ogawa, S. In Carbohydrate Mimics: Concepts and Methods;
Chapleur, Y., Ed.; Wiley-VCH: Weinheim, 1998; p 87. (b) Ogawa, S. In
Carbohydrates in Drug Design; Witczak, Z. J ., Nieforth, K. A., Eds.; Marcel
Dekker: New York, 1997; p 433. (c) Hudlicky, T.; Entwistle, D. A.; Pitzer,
K. K.; Thorpe, A. J . Chem. Rev. 1996, 96, 1195. (d) Ogawa, S.; Hidetoshi,
T. Methods Enzymol. 1994, 247, 136. (e) Ogawa, S. Methods Enzymol. 1994,
2
47, 128. (f) Suami, T. Top. Curr. Chem. 1990, 154, 257.
3) (a) Ogawa, S. In Studies in Natural Products Chemistry, Rahman,
(
A.-U., Ed.; Elsevier Science: New York, 1993; Vol. 13, p 187. (b) Suami,
T. Pure Appl. Chem. 1987, 59, 1509.
(4) Sudha, A. V. R. L.; Nagarajan, M. Chem. Commun. 1998, 925.
Angelaud, R.; Landais, Y. Tetrahedron Lett. 1997, 38, 8841. Verduyn, R.;
van Leeuwen, S. H.; van der Marel, G. A.; van Boom, J . H. Recl. Trav. Chim.
Pays-Bas 1996, 115, 67. Carless, H. A. J .; Malik, S. S. J . Chem. Soc., Chem.
Commun. 1995, 2447. Entwistle, D. A.; Hudlicky, T. Tetrahedron Lett. 1995,
were then prepared by Wittig reaction of hemiacetals 7a ,b
with chloromethylenetriphenylphosphorane followed by de-
13
hydrohalogenation according to Toma and co-workers.
3
6, 2591. Liu, P.; Vandewalle, M. Tetrahedron 1994, 50, 7061. Pingli, L.;
1
4
Vandewalle, M. Synlett 1994, 228. Yoshikawa, M.; Murakami, N.; Yoko-
kawa, Y.; Inoue, Y.; Kuroda, Y.; Kitagawa, I. Tetrahedron 1994, 50, 9619.
Larsen, D. S.; Trotter, N. S.; Stoodley, R. J . Tetrahedron Lett. 1993, 34,
Oxidation at C-5 was carried out with PDC/Ac2O, to yield
ketones 9a ,b, and was followed by Peterson olefination to
15
generate enynes 1a ,b. Enyne 1b underwent radical cycliza-
tion (Scheme 3) by treatment with Bu3SnH and AIBN
8
151. Shing, T. K. M. Cui, Y.-X.; Tang, Y. Tetrahedron 1992, 48, 2349.
Ace n˜ a, J . L.; Arjona, O.; Fern a´ ndez de la Pradilla, R.; Plumet J .; Viso, A. J .
Org. Chem. 1992, 57, 1945. Ley S. V.; Yeung, L. L. Synlett 1992, 291. Cai,
S.; Stroud, M. R.; Hakomori, S.; Toyokuni, T. J . Org. Chem. 1992, 57, 6693.
(
syringe pump addition, 12 h, toluene reflux, 0.02 M) to give
16
alkenyl stannane 4b as the sole isolated product. On the
other hand, reaction of 1a under similar conditions also
afforded 4a as the major compound although accompanied
(
5) Motherwell, W. B.; Crich, D. Free Radical Chain Reactions in Organic
Synthesis; Academic Press: London, 1992. Curran, D. P. Synthesis 1988,
17. Curran D. P. Synthesis 1988, 489.
6) Redlich, H.; Sudau, W.; Szardenings, A. K.; Vollerthun, R. Carbohydr.
Res. 1992, 226, 57.
4
16
(
(
(
7) Maudru, E.; Sing, G.; Wightman, R. H. Chem. Commun. 1998, 1505.
8) Ferrier, R. J .; Middleton, S. Chem. Rev. 1993, 93, 2779. Fraser-Reid,
(11) Crich, D.; Fortt, S. M. Tetrahedron Lett. 1987, 28, 2895.
(12) G o´ mez, A. M.; Danel o´ n, G. O.; Valverde, S.; L o´ pez, J . C. Manuscript
in preparation.
B.; Tsang, R in Strategies and Tactics in Organic Synthesis; Academic
Press: New York, 1989; Vol. 2, Chapter 4.
(13) Mella, M.; Panza, L.; Ronchetti, F.; Toma, L. Tetrahedron 1988, 44,
1673.
(9) (a) G o´ mez, A. M.; Mantec o´ n, S.; Valverde, S.; L o´ pez, J . C. J . Org.
Chem. 1997, 62, 6612. (b) L o´ pez, J . C.; G o´ mez, A. M.; Valverde, S. J . Chem.
Soc., Chem. Commun. 1992, 613.
(14) Andersson, F.; Samuelsson, B. Carbohydr. Res. 1984, 129, c1.
(15) (a) Peterson, D. J . J . Org. Chem. 1968, 33, 780. (b) Ager, D. J .
Synthesis 1984, 385. (c) Pratt, D. V. Hopkins, P. B. J . Org. Chem. 1988, 53,
5885. (d) Carey, F. A.; Frank, W. C. J . Org. Chem. 1982, 47, 3548.
(16) Only one isomeric alkenyl stannane was observed, although the
stereochemistry had not been assigned.
(10) (a) Stork, G.; Baine, N. H. J . Am. Chem. Soc. 1982, 104, 2321. (b)
Stork, G.; Mook, R., J r. J . Am. Chem. Soc. 1983, 105, 3720. (c) Stork, G.;
Baine, N. H. Tetrahedron Lett. 1985, 26, 5927. (d) Stork, G.; Mook, R., J r.
J . Am. Chem. Soc. 1987, 109, 2829.
1
0.1021/jo981989z CCC: $15.00 © 1998 American Chemical Society
Published on Web 11/26/1998

Communications
J . Org. Chem., Vol. 63, No. 26, 1998 9627
Sch em e 3
Several aspects of the synthetic scheme deserve further
comment: (a) In vinyl radical cyclizations10 the 5-exo cy-
clization was found to be largely favored over 6-endo ring
closure.2
2,23
This exo versus endo preference, which has
normally been inverted by inducing reversibility under low
stannane concentration,2
2,23
has occasionally been directed
to the endo mode by substituting the internal position of the
alkene.1
0a,24
In our enyne system (1a ,b) we have included
two elements of regiocontrol to induce the 6-endo ring
closure, the above-mentioned substitution and the strain
associated with the presence of the trans-2,3-O-isopropyli-
dene ring;2
5,26
(b) hydrogen atom transfer to the cyclohexenyl
radical 3 takes place stereoselectively from the R-face of the
molecule, thus generating the stereochemistry at C-5 as-
sociated with sugars of the D-series; (c) the judicious choice
of a 2,3:4,6 di-O-isopropylidene derivative has reduced the
protecting group manipulations in the synthetic scheme to
a minimum; (d) unlike other approaches to carbasugars from
carbohydrates,6 in this protocol a hexose (i.e., D-glucose) is
correlated with its corresponding carbapyranoside (i.e.,
carba-D-glucose); (e) the alkenyl stannane intermediates
4a ,b are valuable precursors for the preparation of carba-
sugar derivatives.
In summary, we have described a new procedure for the
preparation of highly functionalized cyclohexane derivatives
from carbohydrates which features the 6-endo-trig radical
ring closure of a vinyl radical. This protocol has been
successfully applied to the synthesis of 5a-carba-â-D-glucose
and 5a-carba-â-D-galactose pentaacetates. The application
of this method for the preparation of other carbasugars as
well as synthetic transformations of alkenyl stannanes 4a ,b,
aimed at the preparation of carba-C-glycosides and carba-
C-disaccharides27 are underway in our laboratory and will
be reported in due course.
,7
by reduced 11a and the epimer at C-5 12a .16,17 Rapid
addition of Bu3SnH and AIBN to a refluxing solution of 1a
resulted in the exclusive formation of 11a (75% yield). The
final correlation between stannanes 4a ,b and carbasugars
was carried out uneventfully (Scheme 4): acid hydrolysis
Sch em e 4
Ack n ow led gm en t. This research was supported with
funds from the Direcci o´ n General de Ense n˜ anza Superior
(grants: PB96-0822 and PB97-1244). A.M.G. Thanks the
Consejo Superior de Investigaciones Cient ´ı ficas for finan-
cial support. G.O.D. Thanks the Agencia Espa n˜ ola de
Cooperaci o´ n Internacional for a MUTIS scholarship.
followed by acetylation led to alkene 13, ozonolysis followed
by stereoselective reduction (BH3‚SMe2)18 and acetylation
produced penta-O-acetyl carba-â-D-gluco and galacto pyra-
noses 14a 1
9,20
21
21
and 14b ([R] D ) -3.4 (c 0.4, CHCl3), mp )
1
43-145 °C), respectively.
Su p p or tin g In for m a tion Ava ila ble: Experimental proce-
dures and spectroscopic and analytical data for all new compounds
6 pages).
(
17) Compound 12a afforded upon destannylation alkene A which is the
epimer at C-5 of the corresponding alkene B prepared by destannylation of
a .
(
4
J O981989Z
(
(
22) Stork, G.; Mook, R., J r. Tetrahedron Lett. 1986, 27, 4529.
23) Beckwith, A. L. J .; O’Shea, D. M. Tetrahedron Lett. 1986, 27, 4525.
Beckwith, A. L. J .; O’Shea, D. M.; Westood, S. W. J . Am. Chem. Soc. 1988,
10, 2565.
24) Urabe, H.; Kuwajima, I. Tetrahedron Lett. 1986, 27, 1355. Munt, S.
P.; Thomas, E. J . J . Chem. Soc., Chem. Commun. 1989, 480.
(25) Anies, C.; Billot, L.; Lallemand, J .-Y.; Pancrazi, A. Tetrahedron Lett.
1995, 36, 7247. Anies, C.; Pancrazi, A.; Lallemand, J .-Y. Bull. Soc. Chim.
Fr. 1997, 134, 203.
1
(
(
18) Mincione, E. J . Org. Chem. 1978, 43, 1829.
(19) DL mixture: (a) Suami, T.; Ogawa, S.; Nakamoto, K.; Kasahara, I.
Carbohydr. Res. 1977, 58, 240. (b) Ogawa, S.; Ara, M.; Kondoh, T.; Saitoh,
M.; Masuda, R.; Toyokuni, T., Suami, T. Bull. Chem. Soc. J pn. 1980, 53,
1
121.
20) Enantiopure D form: (a) Ogawa, S.; Iwasawa, Y, Suami, T. Chem.
(26) For strain directed 6-endo-dig cyclizations see: Albrecht, U.;
Wartchow, R.; Hoffmann, H. M. R. Angew. Chem., Int. Ed. Engl. 1992, 31,
910. Marco-Contelles, J .; Bernab e´ , M.; Ayala, D.; S a´ nchez, B. J . Org. Chem.
1994, 59, 1234. Breithor, M.; Herden, U.; Hoffmann, H. M. R. Tetrahedron
1997, 53, 8401.
(
Lett. 1984, 355. (b) Ogawa, S.; Iwasawa, Y, Nose, T.; Suami, T.; Ohba, S.;
Ito, M.; Saito, Y. J . Chem. Soc., Perkin Trans. 1 1985, 903. (c) Paulsen, H.;
von Deyn, W. Liebigs Ann. Chem. 1987, 125.
(
21) DL mixture: Suami, T.; Ogawa, S.; Ishibashi, T.; Kasahara, I. Bull.
(27) Angelaud, R.; Landais, Y.; Parra-Rapado, L. Tetrahedron Lett. 1997,
38, 8845, and references therein.
Chem. Soc. J pn. 1976, 49, 1388.