TetmkdronLeaem, Vol. 35, NO. 30. pp. 5513-5516. 1994 Elsevicr scimce Ltd

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Efficient Procedure for the Synthesis of Erythro and Threo

Furanoid GIycals from 2-Deoxyribose

Mohamcdxassouand scrgio castill6n*

Depemment dcQdmia~,UnivcrsilatRovirai Virgili.&a. ImpaialTanwo 1.43005 Tarrsgaok Spai%

Ahstrati Diffemmtly protected srythro aad three ibmnoid glycals hsve been synthesised stsltingti.om2deoxyribo3c,viaseknoxide-ssthekey8tep.

Glycals m useful starting mater&s for the synthesis of enahtiomerically pure c0mpounds.t Recently,

pymnoid glycals have been efIicientIy used as glycosyl donors in the stcreoselcctivc synthesis of Sglycosides via the la&ahydro derivatives2 and 2deoxyglycosides? and furanoid glycals in the preparation of 2’,3’- didcoxy-,4 2’-dcoxy-,5 and C-nucleosidcs .6 Both pyranoid’ and furanoid glycals arc usuauy obtained by rcductivc elimiIWon of appropriately activatbd compounds. Thus, the method of &eland,* which starts from D- ribonolactone and uses Li/NH3(l) as the reductive agent of l-halo-2.3-O-isopropylidmefurano9es. is the method of choice for the synthesis of differently protect& furanoid glycalslo of cry&r0 configuration with silyl ether or acctal protecting groups. Howcvcr, acyl protecting groups must bc avoided and, furthczmorc, glycals of rhreo configumtion need long multistep syntheses to be obtaine!dtt

Scheme 1

RO RO Redastive eliminrsDll Elimination X

The elimination-mediated synthesis of furanoid glycals from 2-deoxycarbohydrates has scarcely been investigated (Scheme 1),4 probably because of the strong acid and-basic media mquired for the elimination, which arc not compatible with the glycal. and the price of the starting mat&al, 2-deoxyribosc, with qard to ribonolactone. However. the later is no longer a problem. In this paper we show that both eryrliro and three fumnoid glycals can be easily obtained &nn 2&oxyribose (1) in hw steps using a key selenoxide elimination, and that this method has allowed us to obtain furanoid glycals with acyl prodecting groups.

Taking advantage of the recently dcscrikd method of the formation of tool ethers by the reaction of acetals with TMSOTft2, wc prepamd the methyl furanoside (3a) from 2-deoxyribose (1) by reaction with HClMeOH (0.05%1)~3 and BnBr/NaH. When 3a was treated with T’MSmf only the 2-benzyloxymethyl-furan could be isolated even when the maction was started at -20°C. The pr#lence of ot& protecting groups such as tBuPh$i led to the total degradation of the starting mat&al. Trying to avoid strong acid or basic media we turned our attention to the pyrolytic elimination of sulphoxidc derivatives. Trcatmcnt of 3a with PhSH/BF3.Et20t4 gave rise to the phcnylthio derivative 4. Oxidation of 4 with 1 c&v. of MCPBA gave the

5513

5514

corresponding sulphoxide and its subsequent pyrolytic elimination by heating in dioxanc or toluene, in the presence or in the absence of base, afforded only the furan. Heating the sulphoxide at reflux in cc14 in the presence of P(OMe)315 did not allow the glycal to be obtained either.

3b R=F’iv

OR 4 R=Bn. X=!Ph 5a R=Bn. X=SePh 5b R=Piv, X&cPh

g) c c ga R=‘BuPh& R’=H

8b R=‘BuPh$i, R’=tBuIU+Si

SC R=R’=H

9a R=Bn 9b R=Ac

a) 1. BnBr. NaH, THP @a). 2. PivCt Py (3b). b) 1. PhSH/BF$t&VX$& -00 (4). 2. mW/q.E~O/C%C~, -5T (5-7a). c) ‘BuPh~SiCi@daml/DMF. d) h4EMCl. Py. e) 1) Tf& Py, OV. 2) ICN&, Wcrown-6, DMF. E) ‘BuMe#CL DBU, bemzme. g) Bu.JW,TW. h) I. al (Sal 2. A+O, Py (9b).

Synthesis of phenyl Zdeoxy-l-selmo-D-mytim and hmAmanosides. The drastic conditions needed for the elimination of sulphoxides led to the aromatisation of the glycal. Recently, phenyl I-selenopyranosides have been synthesised by treating peracetylated sugars with PhSeH. 16 As the selonoxide derivatives undergo elimination at low temperature, we synthesised differently protected phenyl 2-deoxy-1-seleno-eryrhro-and ~hreo-furanosides (Scheme 2). Thus, methyl 2deoxyfuranosides 3a. 3b and 6, easily prepared from 2. were converted into phenyl2deoxy-l-selenofuranosides Sa, 5b and 7a (a/l3 mixture) in 85%, 71% and 75% yields respectively, by reaction with PhSaH and B@Et20. The tBuPh2Si group appeared to be stable enough under the conditions of PhSeH introduction when the temperature was maintained at -5°C. Prom compound 7a differently protected derivatives can be obtain&t for instance, 7b was prepared by treatment with MEMCl.

Interestingly, the configuration of the secondary alcohol in compound 7a was inverted by ma&on with Tf2O/Py and KNQ918-crow&/DMF~~ sffording three derivative 80 in 75% yield for the two steps (Scheme 2). Protection of the seeo&uy alcohol with &&ie$3iCl led to compound Sb.

In the same way, the treatment of 8s with Bu.+NP gave quantitatively the unprotected compound fk, from which the phenylseleno derivatives 9a and 9b were easily obtained by usual protection methods.

An alternative way of synthesixing three derivatives could be the inversion of co&uration in 6 followed

by protection, but PhSe introduction fails in this case.

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Table 1. Synthesis of furanoid glycals from phenyl2-deoxy-1 -s&no-furanosidesa

Pbenyl I-selaro derivative

Glycalis =WW

1 *Ph sa 10a 85

2 sePb Sb

opiv

lob

3 SePh

7b 1oc

4

5 w&sdh 9a -& llb

71

73

74

82

6 7ob

*Rea&x~s were performed at a 0.2 mm01 scale. in CH$l2, at 0 “C, witi a 1: 1:l. 1: 1 sa&Pr2EtN~aOOlVWO+r)~ ratio. b Sample of pure material by ‘I-l NMR. It partiany decMnposc on c lrromatographic puriflu&n.

Synthesis of furanoid glycals. FVelimins.ry oxidation experiments of phenyl I-selenofuranoside Sa with

Hz02 in TlW led directly to glycal1Oa in 30% yield as the best result (Fable 1). Use of MBBA gave rise to

decomposed products where no glycals could bc detected. Oxidation of Sa with tBuOOHlS in CH2ClS did not

produce the selenoxide but only starting material was recovered even after heating in refluxing CH2Cl2 for two

hours.

Addition of Ti(oiPr)420 to a mixture of Sa and tBuOOH cooled to OY! caused the fast oxidation of the

selenium leading cleanly to glycal1On with a 85% yield (Table 1, Entry 1). Similarly, compounds 7b, 8b and 9a (l3ntries 3.4 and 5) were converted into glycals 10~. lla and lib with yields above 70%. It is noteworthy

that ester21 containing phenylseleno derivatives Sb and 9b (Entries 2 and 6) also gave glycals lob and llc, respectively, under the same reaction conditions, and that lob ([a]D =+188. c 2, CHC13) was isolated and

CharactCliSCd.

In conclusion, the oxidation of phenyl2-deoxy-1-seleno-furanosides with the tWKlO~(Ol~)4 system

is an efficient and versatile procedure for the synthesis of furanoid glycals, allowing one to obtain eryfko and three furanoid glycals from 2-deoxyribose. The method is compatible with different protecting groups such as

methyl, benxyl or silyl ethers, acetals and even ester. Compounds l&n and 10~ were made in a 1-2 g scale.

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Acknowledgement: This rexarch was suppomd byDc31cX~ (~inisterio de R~~IIXCSI y ciencia. spit& Grant PB92-05 10.

Referencea and Notas 1. 2. 3.

8.

9. 10.

11. 12. 13. 14. 15. 16.

17.

18.

19. 20. 21.

Hanessian, S. Total Synthesis of Natural PK&ICU: lltc Chit-on Approach’ Pergamon Press. Gxfonl, 1983. Dushin, R.G.; Danishefsky, S.J. J. Am. Chem. Sot. 1992,114,347 1. a) Roush, W.R.; Liu. X-F. Tetrahedron Len. 1993,34,6829. b) Kaila, N.; Gmwal, G.; Frau&, RW. J. Org. Chem. l!H2,57 2084. c) Horton, D.; Priebe, W.; Smaidman, M. Curbohydr. Res. l9!IO,205,71. d) Thiem, J.; KlafIbe, W. J. Org. Chent. 1989,54,2006. e) Beau, J.M.; Jaurand, G. Tetrahedron L&t. 1989,30,75. f) Kaye, A.; Neidle, S.; Reese, C.B. Tetrahedron L&t. 1988,29,2711. g) Preuss. R Schmidt, RR. Synthesis 1988,694. h) Jaurand, G.; Beau, J.M.; Sinay, P. J. Chern. See. C&m. Commun. 1981,527. Kim, C.U.; Misco, P.F. TetrahedronLett. 1992,33.5733. b) Bolitt, V.; Chaguir, B.; Sinou, D. Tetrahedron Lett. 1992,33,248 1. El-Laghdach. A.; Dfaz, Y.; CastilMn, S. Tetrahedron Lett. V&&34,2821. a) Doyle-Daves, G.; Hallberg, A. C&u. Rev. 1989.89.1433. b) Doyle-Daves. G. Act. Chem. Res. l990. 23.201. From hslopyranoses: a) (Zu/AcOH): Roth, W.; Pigman, W. Met& Carbohydr. Chem. 1963,2.405. b) Shafixadeh, F. Methods Carbohydr. Chem. 1%3,2,409. (Za in neutral medium): c) Holxapfel, C.W. ; Koekemoer, J.M.; Verdoom, G.H., S. &r. J. Gem. 1986,39,151. d) Csuk, R.; FUrstner, A.; GHnzcr, B.I.; Weidmann, H. J. Chem. Sot. Chew. Common. 1986.1149. From phenyl 1-thio-pyranosides: (Cl&Li): (e) Fem$ndez-Mayoralas, A.; Mart-a, A.; Trumtel, M.; Veyri&res,A.;Sinay, P. Carbohydr. Res. 1989,188,81. Ireland R.E.: Wilcox, C.S. Tetrahedron Lett. 1977.2389. b) Ireland, RE.; Wilcos, C.S.: Thaisrivongs. S. J. Org. Chem. 1978.43,786. c) h&nd R.E.; Tbaisrivongs. S.; Vauier, N.; Wilcox, C-S. J. Org. Chem. 1980,45,48. d) Abramski, W.; Chmieiewski, M. J. Carbohydr. Chem. 1994,13,125. Chi-Ya Cheng J.; Hacksell, U.; Doyle-Daves, G. J. Org. Chem.. 1985,50,2778. other methods of preparation of furanoid glycals from 1-halofuranoses: a) (Zn/Ag-graphite) See ref 7d. b) (CleH7Na) Eitehnan, S.J.; Hail, R-H.; Jordaan, A. J. Chum. Sot.. Perkins Trans I. 1978.595. c) (NafT’HF) Eitelman. S.J.. Jordam, A. J. Chem. SOL, Chem. Commun. 1977,552. Obayashi, M.: Schlosser, M. Chem. Len. NW. 17 15. Gassmau, P.G.; Burns, S.J.; Pfister, K.B. J. Org. Chem. 1993,58, 1449. Hansen, P.; Pedersen. E.B. Act. Chem. Scund. 1990,44,522. Chauteloup, L.: Beau, J.M. Tetrahedron Lett. 19!32,33,5347. Solaja B.; Huguet, J.; Karpf, M; Dmiding, A.S. Tetrahedron f&t. 1987.28.4875. a) Mehta, S.; Pinto, M. .I. Org. Chem. 1993,58,3269. b) Witcxak, Z.J.; Whistler, RL. ffeteroycles 1982, 19, 1719. Moriarty, R.M.; Zbuaug, H.; Peumasta. R.; Liu, K.; Awastbi, A.K.; Tuladhar, S.M.; Rae, M.S.C.; Singh, V.K. Tetrahedron fett. 1993,34,8029. All glycals (except compound llc which was not isolated) gave correct Elemental Analysis and spectroscopical data. Selected NMR (CDCl3.8 in ppm) data for glycals: (Ma) (lH) 6.58 (d, Jl,z=2.7 Hz. H-l), 5.15 (dd, H-2); (‘3C) 150.4 (C-l), 100.6 (C-2). (llb) (*H) 6.62 (d. JJ2=2.6 Hz, H-l), 5.15 (dd, H-2); (‘3C) 151.6 (C-l), 199.5 (C-2). (11~) (II-I) 6.53 (d, J12=2.4 Hz, H-l), 5.15 (dd, H-2); (‘SC) 150.3 (C-l), 101.0 (C-2). (12a) (lH) 6.63 (d. J12=2.1 Hz, H-l), 5.08 (dd, H-2); (13C) 149.6 (C-l), 103.9 (C-2). (l2b) (&I) 6.64 (d, Jt,g=2.6 I-Ix, H-l), 5.26 (dd, H-2); (‘3c) 150.6 (C-l), 101.4 (C-2). (l2c) (III) 6.68 (d, Jts=2.4 Hz, H-l), 5.23 (dd, H-2): (‘3C) 151.7 (C-l), 100.9 (C-2) Hori. T.: Sbarpples, K.B. J. Org. Gem. 1978.43.1689. Brunetiere. A.P.; Lallemand, J.Y. Tetrahedron L&t. 19%8,29,2179. For another mferencc describiig acyl protected furanoid glycals see: Ness, R.K.; Fletcher, H.G. J.Org. Chem. 1963,28,435.

(Received in UK 15 April 1994; revised 27 May 1994; accepted 3 June 1994)