6762 (1970), and references therein; (b) P. H. Kasai and D.McLecd, Jr., bid., 94, 720 (1972). (29) H. Nakatsuji, J. Am. Chem. SOC.,96, 24, 30 (1974). (30) Langhoff and DavidsonaCnote that their extensive calculation of methylene shows bent bonds, but they do not discuss the implications of the Hellman-Feynman theorem. The theorem is not satisfied by their results, and it would be interesting if including polarization functions on the hydrogens would improve the agreement. (31) R. C. Bingham and M. J. S. Dewar, J. Am. Chem. SOC., 95, 7180 (1973).
1
1
N-Me
2 '6"6 p Me-C6H4-S03H
J. Michael McBride Department of Chemistry, Yale University New Haven, Connecticut 06520 Received February 15, 1977
A Novel Synthesis of 1,2-cis-Disaccharides' Sir: Much effort is currently devoted to the efficient and stereocontrolled preparation of 1,2-~is-disaccharides.~The availability of a general procedure is of paramount importance as it opens the way to many biologically and clinically active Me substances like antibiotics and antigens. As the scope for im5 4 provement of existing methods appears to be limited, novel ,. reactions are desirable. The discovery in our laboratory that secondary amides react smoothly with halogeno sugars in the presence of a silver salt to give a new class of imidates paved the way to a novel method of selective activation of the anomeric center of carbohydrates, which appears full of promise in the field of glycosidic synthesis as amply demonstrated LR-H herein through the practical approach to eleven disacchar8 R = 2,3,4,6-tetra-~-benzyl-m-~-glucopyranosyl ides. 9 R = 2,3,4-tri-~-benzyl-a-~-fucopyranosyl A benzene solution of 2,3,4,6-tetra-0-benzyl-a-~-gluco6 12 R = 2,3,4,6-tetra-~-benzyl-o-~-galactopyranosyl pyranosyl chloride3 (1 equiv) was stirred for 12 h at room temperature in the presence of N-methylacetamide (1 equiv), Table I. a-L-Fucosylation of Various Alcohols Using the lmidate silver oxide (3 equiv), diisopropylethylamine, and powdered Derivative 13 4-A molecular sieves to give 1-0-(N-methy1)acetimidylProtected disaccharide Yield,a Mp [~]*OD,~ 2,3,4,6-tetra-0-benzyl-P-~-glucopyranose (1, 88%) as a syrup, Alcohol (or trisaccharide) 96 O C degree [ a I 2 O ~ 28.6' (c 1.51, CHC13).5The stereospecificity of this attack may be attributed to a push-pull mechanism at the 2 16 74 -65.5 surface of the insoluble silver oxide. This reaction is general I 9 92 116-117 -118 14 17 84 129-130 +3 and a variety of benzylated imidates have been prepared.6 They 93 87-88 +2 15 18 all react with alcohols in various solvents and in the presence 86 +I9 19 20 of p-toluenesulfonic acid to give a good yield of a-gluco~ides.~ A study of this glucosylation reaction using various imidates a No evidence for the formation of 0 anomer was obtained in any has shown that 1 is the best suited for this purpose. of the experiments. In chloroform, c 1. In a typical procedure, methyl 2,3,6-tri-O-benzyl-a-~lyzed conditions.2c When benzyl 3,4,6-tri-O-benzyl-P-D-gaglucopyranoside8 (2) was chosen as a crucial model for glulact~pyranoside'~ was glucosylated with 1, the disaccharide cosylation at the redoubtableg 4-hydroxyl group of a hexopyderivative 6 was obtained (90%) as a pure foam, [ a I 2 O+23O ~ ranoside derivative (4C1 chair form). A solution of aglycon 2 (c 1, CHCl3). A further example of effective a-glucosylation (0.5 mmol) in dry benzene (20 mL) was treated at room temwas provided by the reaction of 1with 1,2:5,6-di-O-isopropyperature with the imidate 1 (0.75 mmol) and p-toluenesulfonic lidene-a-D-glucofuranose (7), where the protected disaccharide acid (0.5 mmol) under rigorously anhydrous conditions. The 8 was obtained in crystalline form (70%), mp 90-91 OC, [a]20D solution was stirred for 6 days and neutralized with triethyl+46O (c 2, CHC13). A small amount of crystalline P anomer amine. After workup and purification (silica gel column), (396) was isolated, mp 118-119 "C, [ a l 2 O D + l o (c 1, methyl 2,3,6-tri-0-benzyl-4-0-(2,3,4,6-tetra-0-benzyl-aCHC13). D-ghcopyranosy1)-a-D-ghcopyranoside was isolated as a clear This imidate procedure was then applied to stereospecific syrup (3,85%), [aI2'D +48O (c 1.05, CHC13). After catalytic a-L-fucosylations, as a-L-fucose containing oligosaccharides hydrogenolysis (Pd/C), methyl a-maltoside was obtained as are of widespread occurence in living systems. Under the ~ a foam (85%, [ a l z o+172.5O.I0 Similar glucosylation of methyl 2,4,6-tri-O-benzyI-a-~- agency of the Vilsmeier reagent,4 2,3,4-tri-O-benzyl-a-~fucopyranose14 (1 1) was conveniently transformed into crysglucopyranoside8 (20 h) followed by column chromatography talline 2,3,4-tri-0-benzyl-au-~-fucopyranosyl chloride (12, gave the disaccharide derivative 4 as a colorless foam (81%); 92%), mp 72-73 OC, [CY]~OD-169O (c 1, CH2C12), which was likewise, the isomaltoside 5 was obtained (80%), mp 101.5 "C [ c Y ] ~ ~ +59.3' D (C 1.78, CHC13).'' in turn converted into l-O-(N-methyl)acetimidyl-2,3,4-tri0-benzyl-0-L-fucopyranose (13,90%), mp 89-90 OC, [ a l * O ~ The 2-hydroxyl group of D-galactopyranosides has been glucosylated in poor yield (25%) using either 2,3,4,6-tetra-67O (c 1, C6H6). The imidate 13 has been most successfully used for the preparation of various protected di- and trisac0-benzyl-a-D-glucopyranosylchloride2b or 2,3,4,6-tetra-0charides, as shown in Table I. Owing to its crystallinity, its benzyl-a-D-glucopyranosylbromideI2 under halide ion cataI
I
-
+
Journal of the American Chemical Society
/
99:20
/ September 28, 1977
6763 (10) A value of t174’ (c 0.9,water) was reported fcf pure methyl a-maltoside: W. E. Dick, Jr., D. Weisleder, and J. E. Hodge, Carbohydr. Res., 18, 115
(1971). (11) In this case, -15% of the p anomer was present in the reaction mixture,
as shown by GLC. The pure p anomer was isolated in small amount after t17.1’ (c 0.42, column chromatography, mp 133-133.5 OC, [ a ] 2 0 D CHC13). (12)P. J. Garegg, I.J. Goldstein, and T. Iversen, Acta Chem. S c a d . 8, 30,876
I OBn
13
13
12
d
R = Bo R = A
ok
1 6R
= Me,R’ = OBn, R”=Bn 17 R = Bn, R ’ = NHAc,R”= Bn
-
18 R = En, R ’ = NHAc, R ” = A
(1976). (13)J. C. Jacquinet and P.Sinay, Tetrahedron, 32, 1693 (1976). (14)M. Dejter-Juszynski and H. M. Flowers, Carbohydr. Res., 18, 219 (1971). (15)In the case of the three amorphous disaccharides 3,4,and 10,no anomer was detectable using ’H NMR spectroscopy.
Acpoq
Jean-Ren6 Pougny, Jean-Claude Jacquinet, Mahmoud Nassr Danielle Duchet, Marie-Louis Milat, Pierre Sinay*
AcO
‘
VBn B
Laboratoire de Biochimie Structurale U.E.R.de Sciences Fondamentales et Appliqukes 45045 Orlkans Ckdex, France Receiued May 27, 1977
OBn
I
Stepwise Reduction of the Carbon-Nitrogen Triple Bond of Acetonitrile on the Face of a Triiron Nonacarbonyl Cluster
n
Sir: The use of transition metal clusters as homogeneous catalysts’ and stoichiometric reagents2 is currently of great interest.3 Metal atom clusters permit a greater variety of interacBnO tions with substrates than is possible in mononuclear comBn = CH c H plexes. Some examples can be cited for the cluster chemistry II 2 6 5 A = CH -CH=CH N-Me of but an even richer field has been found for ru2 2 3 thenium and o s m i ~ m . ~This ~ , greater ~ , ~ diversity of interactions stability and its ease of preparation from hemiacetal 11, the is also believed to be responsible for the ability of clusters to imidate 13 appears as an efficient a-L-fucosylating agent. carry out reactions which mononuclear species generally can Further use for the syntheses of blood group substances is now not, such as the reduction of triple bonds.3bWe report here the under way in our laboratory. preparation of a unique series of complexes (Scheme I) which Finally, l-O-(N-methyl)acetimidyl-2,3,4,6-tetra-0-benclearly delineate a sequence for the reduction of the carbonzyl-6-D-galactopyranose (21) was used to prepare the pronitrogen triple bond of a n organic nitrile on the face of an tected disaccharide 10 (74%) as a glass, [ a I 2 O+33O ~ ( c 1.1, Fe3(C0)9 cluster. CHC13).” In an attempt to extend our studies of hydridocarbonyl The examples reported herein prove that this novel approach cluster chemistry6 to that of the more common metals we is of wide applicability for the preparation of a wide variety of treated W(C0)sI- with Fe2(C0)g2- in refluxing acetonitrile. di- and oligosaccharides. The resulting anion mixture (later shown to contain 2)7awas acidified and the neutral product thus obtained was analyzed References and Notes by mass spectrometry. Surprisingly, it contained no tungsten, Research supported by Centre National de la Recherche Scientifique, Inbut it did contain the elements of a molecule of acetonitrile. stitut National de la Sante et de la Recherche Medicale and Delegation Spectroscopic data7b indicated structure 3 which has been G6nerale a la Recherche Scientifique et Technique (ASCO, Grant No. 74 7 0973 and 75 1 1364). confirmed by an x-ray determinatior8 The tungsten by(a) G. Wulff and G. Rohle, Angew. Chem., int. Ed. Engl., 86, 173 (1974); product was determined to be W(C0)3(CH3CN)3. W e have (b) P. A. Gent and R. Gigg, J. Chem. Soc., Perkin Trans. 1, 1446 (1974); subsequently found that anion 2 is also formed by the base (c) R. U. Lemieux, K. B. Hendricks, R. V. Stick, and K. James, J. Am. C b m . Soc., 97,4056 (1975);(d) K. Igarashi, J. Irisawa, and T. Honma, Carbohydr. disproportionation reaction9 of Fe(C0)S in moist acetonitrile, Res., 39,341 (1975);(e) D. E. lley and B. Fraser-Reid, J. Am. Chem. Soc., presumably via HFe3(C0)11- (1) (vide infra). Some 97,2563 (1975). This chloride was conveniently prepared in one step (85%) from comHFe(C0)4- as well as iron metal also forms. The HFe(C0)4mercially available 2,3,4,6-tetra-O-benzyl-a-~-glucopyranose(Pfanstiehl, decomposes when sodium iodide is included in the reaction Waukegan, U.S.A.), under the agency of dimethylchloroformiminium mixture, thereby facilitating workup.l0 The only apparent chloride (prepared from dimethylformamideand phosphorus pentachloride according to ref 4). reference to acetonitrile-induced base disproportionation of H. H. Bosshard, R. Mory, M. Schmid, and Hch. Zollinger, Helv. Chim. Acta, Fe(C0)s is a patent claiming Fe(C0)S as a catalyst precursor 42, 1653 (1959). All new compounds gave correct microanalyses and exhibited IR and NMR for the hydrogenation of nitriles to amines (500-5000 psi H2, spectral characteristics that were in accord with their structures. 100-300 OC).” The existence of metal carbonyl infrared See J. R. Pougny and P. Sinay, Tetrahedron Lett., 4073 (1976),for the spectral changes was noted (but not documented) in that work syntheses of some aromatic imidates. Except in acetonitrile where a majority of -glucoside was obtained, preduring preparation of the catalyst from Fe(C0)s in refluxing sumably through a nitrilium intermediate. Benzene was finally selected acetonitrile. as a standard solvent, but the nature of the solvent was not optimized in each specific case. The neutral product HFe3(CO)g(CH3C=NH) (3) is slowly J. M. Kuster and I. Dyong, Justus Liebigs Ann. Chem., 12,2179 (1975). air oxidized in solution to give Fe3(C0)9(CH3C=N) (6a)12 When methyl 2,3,6-tri-O-benzyl-a-o-glucopyranoside was partnered with in 20% yield. (The remaining iron can be approximately ac2,3,4,6-tetra-O-benzyl-a-~-glucopyranosylbromide according to Lemieux et aL2‘ no disaccharide was formed. In general many difficulties have been counted for as Fe(C0)s and iron oxide.) Significantly, 6a could experienced with the glycosylation of the 4-hydroxyl group of glucopyranot be prepared directly from either Fe3(C0)12 or Fez(C0)9 noside derivatives and it is only recently that a practical synthesis (44%) of a maltose derivative has been described.2d and acetonitrile. It (6a) can, however, be hydrogenated back OBn
qb\,w
kl
Communications t o the Editor
