Organometallics 1996, 15, 2585-2587
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Oxidative Addition of py(dmgH)2Co-Na+ to a Ribofuranosyl Bromide: An Unusual Reaction with the Cobaloxime Ligand Rachel M. Slade and Bruce P. Branchaud*,† Department of Chemistry, University of Oregon, Eugene, Oregon 97403-1253 Received October 10, 1995X Summary: Reaction of 2,3,5-tri-O-benzoyl-β-D-ribofuranosyl bromide (12) with NaCo(dmgH)2py (dmgH ) dimethylglyoxime monoanion) in CH3CN was expected to proceed by normal oxidative addition to the carbonbromine bond to form 2,3,5-tri-O-benzoyl ribofuranosyl cobaloxime (4) with a carbon-cobalt bond in place of the carbon-bromine bond. Instead, the major products, the isomeric (mixture of R- and β-anomers) dimethylglyoxime adducts 1-O-(dimethylglyoximato)-2,3,5-tri-Obenzoyl-D-ribofuranosides (17), were the result of reaction at the oxygen of the dimethylglyoxime ligand rather than at the cobalt. It is well-known that the stability of the carbon-cobalt bond in coenzyme B12 model compounds, such as alkylcobaloximes, is strongly dependent upon the structure of the alkyl group. In the case of alkylcobaloximes, methyl and primary alkyls are stable and isolable, secondary alkyls are somewhat unstable but usually isolable, and tertiary alkyls are usually unstable and cannot be isolated.1 The trend in stabilities can be attributed to weakening of the carbon-cobalt bond with increasing alkyl substitution due both to steric destabilization (lengthening) of the carbon-cobalt bond2 and to stabilization of alkyl radicals with increasing substitution. The major decomposition pathway for coenzyme B12 model compounds such as cobaloximes is usually via β-H elimination to form an alkene and a cobalt hydride (eq 1). If
β-H species are not present in the alkyl group, slow radical-radical dimerization can occur, as in the case of PhCH2CoIII[C2(DO)(DOH)pn]I (1), for which a novel radical addition to the [C2(DO)(DOH)pn] ligand has been observed (Scheme 1).3 We have been studying the preparation and reactions of glycosylcobaloximes such as (2,3,5-tri-O-benzoylribofuranosyl)cobaloxime (4), (2,3,4,6-tetra-O-benzoylD-glucopyranosyl)cobaloxime (10), and (2,3,4,6-tetra-Obenzoyl-D-mannopyranosyl)cobaloxime (11) with the aim of applying cobaloxime-mediated radical cross-coupling †Phone: (503) 346-4627. Fax: (503) 346-4645. E-mail: bbranch@ oregon.uoregon.edu. X Abstract published in Advance ACS Abstracts, May 1, 1996. (1) Brown, K. L. In B12; Dolphin, D., Ed.; Wiley: New York, 1982; Vol. 1, pp 245-294. (2) Gerli, A.; Sabat, M.; Marzilli, L. J. Am. Chem. Soc. 1992, 114, 6711-6718 and references cited therein. (3) Daikh, B. E.; Finke, R. G. J. Am. Chem. Soc. 1991, 113, 41604172.
S0276-7333(95)00795-3 CCC: $12.00
Figure 1. Scheme 1
Scheme 2
reactions toward the preparation of C-glycosides and C-nucleosides. We were especially interested in preparing ribofuranosylcobaloxime 4, a derivative of D-ribose, with the aim of developing a cobaloxime-mediated synthesis of the C-nucleoside antitumor antibiotic showdomycin (7), as outlined in Scheme 2. In contrast to the easy preparation of six-membered-ring pyranosylcobaloximes such as 10 and 11 (eq 2), all attempts to
prepare five-membered-ring ribofuranosyl cobaloxime 4 © 1996 American Chemical Society
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Organometallics, Vol. 15, No. 11, 1996
failed. Instead, we observed a new type of reaction, which is the topic of this communication. Standard cobaloxime-forming conditions4 were used in the addition of NaCo(dmgH)2py, prepared by NaBH4 reduction of ClCo(dmgH)2py,5 to the alkyl halide in deoxygenated methanol. Using such conditions, (2,3,4,6tetra-O-benzoyl-D-glucopyranosyl)cobaloxime (10) was synthesized from 2,3,4,6-tetra-O-benzoyl-D-glucopyranosyl bromide (8) in 89% isolated yield after silica gel chromatography and (2,3,4,6-tetra-O-benzoyl-D-mannopyranosyl)cobaloxime (11) was synthesized from 2,3,4,6-tetra-O-benzoyl-R-D-mannopyranosyl bromide (9) in 77% isolated yield after silica gel chromatography.6,7 In contrast, treatment of 2,3,5-tri-O-benzoyl-β-D-ribofuranosyl bromide (12) under the same conditions led rapidly to the formation of the corresponding 1-methyl2,3,5-tri-O-benzoylribofuranoside. The exceptional solvolytic lability of ribofuranosyl halides such as 2,3,5tri-O-benzoyl-β-D-ribofuranosyl bromide (12) made this standard method unsuitable for the preparation of 2,3,5tri-O-benzoylribofuranosyl cobaloxime (4). Previous work in our laboratories with highly reactive alkyl halides has shown that dry CH3CN is an ideal solvent to suppress ionic reactivity yet allow radical reactions to proceed smoothly.8 When the CH3CN conditions were used with 2,3,5-tri-O-benzoyl-β-D-ribofuranosyl bromide (12), (2,3,5-tri-O-benzoylribofuranosyl)cobaloxime (4) was not formed. Instead, the major products, isolated in as high as 60% yield, were the isomeric (mixture of R- and β-anomers) dimethylglyoxime adducts 1-O-(dimethylglyoximato)-2,3,5-tri-O-benzoyl-D-ribofuranoside (17).9 The structure of the major products 17 is fully consistent with the 1H NMR, and 13C NMR, lowand high-resolution MS data summarized in ref 9. Two mechanisms are proposed for the formation of 17, one radical and the other ionic (Scheme 3). The (2,3,5-tri-O-benzoylribofuranosyl)cobaloxime (4) is probably formed transiently, but due to stereoelectronic reasons (see below) it rearranges by either radical and/ or ionic processes to form 16, with the anomeric position of the ribofuranoside covalently bonded to an oxygen of a dimethylglyoxime ligand of the Co(dmgH)2py complex. Formation of 16 disrupts one of the two key hydrogen bonds that hold the dimethylglyoxime ligand together around cobalt, so that 16 likely falls apart to produce 17, either in a direct manner or during workup. These data highlight the sharp reactivity and stability distinctions between the two carbohydrate systems involved. Why is the alkylcobaloxime chemistry of pyranoses (conversion of 8 to 10 and 9 to 11) so different from that of the furanose (12 to 17 and not to 4)? The main difference can be attributed to the significantly stronger anomeric effect exhibited by furanoses com(4) Branchaud, B. P.; Meier, M. S.; Malekzadeh, M. N. J. Org. Chem. 1987, 52, 212-217. The procedure was modified only by using NaCo(dmgH)2py generated by direct NaBH4 reduction of ClCo(dmgH)2py, instead of its in situ formation as described in this reference. (5) ClCo(dmgH)2py was prepared as described by: Schrauzer, G. N. In Inorganic Synthesis; Jolly, W. L., Ed.; McGraw-Hill: New York, 1968; Vol. 11, pp 61-70. (6) Glycosyl cobaloximes 10 and 11 were characterized by 1H, 13C, IR, MS, and high-resolution MS. (7) The preparation of glycosylcobaloximes from NaCo(dmgH)2py and glycosyl halides has also been accomplished under aqueous conditions, buffered to minimize glycosyl halide solvolysis: Ghosez, A.; Gobel, T.; Giese, B. Chem. Ber. 1988, 121, 1807-1811. (8) (a) Branchaud, B. P.; Detlefsen, W. D. Tetrahedron Lett. 1991, 32, 6273-6276. (b) Branchaud, B. P.; Slade, R. M.; Janisse, S. K. Tetrahedron Lett. 1993, 34, 7885-7888.
Communications Scheme 3
pared to pyranoses. The anomeric effect can be defined as bonding of a filled orbital from a heteroatom (in these cases, the oxygen in the ring) with the σ* antibonding C-X bond at the anomeric carbon.10 Conformational effects in five-membered-ring furanoses provide better torsion angles to achieve more orbital overlap (larger (9) ClCo(dmgH)2py (1.315 g, 3.26 mmol) was added to a stirred solution of CH3CN (30 mL) in a flame-dried three-necked 100-mL round-bottom flask. The solution was deoxygenated by bubbling N2 into the CH3CN through a syringe needle while the temperature was lowered to 0 °C. NaBH4 (0.139 g, 3.67 mmol) was added in portions over a few minutes until the solution turned dark green-black. A solution of 12 (2.71 mmol) in 4 mL of deoxygenated anhydrous THF was added via cannula, the flask was wrapped in foil, and the solution was stirred in the dark at 0 °C for 1 h under positive N2 pressure. Cooling was removed, the reaction mixture was stirred for 2.5 h and then cooled to 0 °C, and 8 mL of deoxygenated acetone was added. The solution was adsorbed onto 0.8 g of silica gel, which was evaporated to dryness with a rotary evaporator; the silica gel was then placed on top of a column of 8 g silica gel under N2 for chromatography using deoxygenated EtOAc for elution. Two additional column chromatographies using hexanes-EtOAc (1:2 and 3:1) for elution provided 17 as a pure mixture of epimers at the anomeric C-1 position in a ratio of roughly 2:1 (it is unclear which is the R- or β-anomer). 1H NMR: (300 MHz, CDCl3; contains both anomers): δ 2.00 (s, 6H), 2.10 and 2.14 (2s, 6H), 4.32-4.34 (m, 1H), 4.44-4.56 (m, 2H), 4.67-4.80 (m, 4H), 5.08-5.10 (m, 1H), 5.46 (t, 1H; J ) 4.8 Hz), 5.92 (d, 1H; J ) 3.6 Hz), 5.99 (s, 1H), 6.36 (d, 1H; J ) 4.2 Hz), 7.33-8.05 (m, 30H). 13C NMR: δ (contains some overlapping peaks) 9.45, 10.46, 10.64, 62.41, 64.45, 72.03, 72.86, 74.74, 76.05, 79.21, 79.50, 105.80, 107.77, 124.53, 126.01, 128.17, 128.33, 128.41, 128.46, 128.52, 128.91, 129.72, 129.83, 133.15, 133.37, 133.50, 135.72, 154.78, 155.05, 156.94, 157.03, 165.14, 165.31, 165.57, 166.06. IR (NaCl, thin film): 3443, 3090, 2850, 1735, 1460, 1370, 1277, 1094, 979, 720 cm-1. LRMS (Magic Bullet + NaI): m/z (relative intensity) 584 (15%, M + Na), 445 (30%, M - dimethylglyoxime), 105 (100%, PhCO), 77 (70%, Ph). HRMS: calcd for C30H29N2O9Na 584.1771, found 584.1758. (10) (a) Thatcher, G. R. J., Ed. The Anomeric Effect and Associated Stereoelectronic Effects; American Chemical Society: Washington, DC, 1993. (b) Juaristi, E.; Cuevas, G. Tetrahedron 1992, 48, 5019. (c) Deslongchamps, P. Stereoelectronic Effects in Organic Chemistry; Pergamon Press: Oxford, U.K., 1983.
Communications
anomeric effect) than in six-membered-ring pyranoses.11 The C-X bond involved in an anomeric type of interaction is typically a C-O bond or a C-halogen bond (as in 8, 9, and 12), but the concept of an anomeric effect applies equally well to the C-Co bond in alkylcobaloximes such as 4, 10, and 11. Thus, in analogy to more commonplace anomeric effects comparing pyranoses with furanoses,11 donation of an electron pair from the ring oxygen into the C-Co σ* antibonding orbital should be more effective for a furanose such as 4 than for pyranoses such as 10 and 11. The extra weakening of the C-Co bond in furanoses compared to pyranoses is apparently sufficient to make 4 unstable, whereas 10 and 11 are both stable and isolable. It is important to note that the anomeric effect argument for C-Co bond weakening should apply whether radical or ionic mechanisms of C-Co bond cleavage are considered, since an anomeric effect can stabilize either radical or cation intermediates. A complete interpretation of our results based on the anomeric effect then is (1) 4 should have a very weak C-Co bond, (2) ionic or radical C-Co bond cleavage in 4 will be very facile due to the anomeric effect, (3) 16 (ribofuranoside attached to O of dimethylglyoxime in Co(dmgH)2py) might be formed directly or 18 (ribofuranoside attached to C of dimethylglyoxime in Co(dmgH)2py) could be formed transiently, (4) if 18 is formed transiently, it should have a weak C-C bond due to both the anomeric effect and the unique set of structural features which make that type of bond weak in the analogous complex 3 (and thus make 3 a transient intermediate), and (5) 16 should eventually be formed (11) Cosse-Barbi, A.; Watson, D. G.; Dubois, J. E. Tetrahedron Lett. 1989, 30, 163-166.
Organometallics, Vol. 15, No. 11, 1996 2587
Figure 2.
as the most stable isomer of the three isomers 4, 16, and 18 since 16 should have a strong and stable C-O bond. In summary, oxidative addition of py(dmgH)2Co-Na+ to the unusually reactive 2,3,5-tri-O-benzoyl-β-D-ribofuranosyl bromide (12) provided new insight into a previously unobserved mode of substrate-ligand reactivity for coenzyme B12 model complexes such as cobaloximes. Although the results are unexpected, they can be understood using the concept of the anomeric effect and its stronger expression in furanoses compared to pyranoses. Acknowledgment. This work was supported by the NSF (Grant No. CHE 8806805) and a fellowship from the Department of Education GAANN program (R.M.S.). Supporting Information Available: Text giving preparation details and characterization data for the compounds synthesized in this paper (7 pages). Ordering information is given on any current masthead page. OM950795W
