J. Org. Chem. 1990, 55. 5700-5710
5700
Conclusion AM1 and ab inito STO 3G MO calculations on bicyclo[2.2.2]oct-l-y1 cation and 2- and 3-substituted derivatives suggest that the carbonyl and imine functions in 3-oxo- (13) and 3-(E)-iminobicyclo[2.2.2]oct-l-yl(15) cations are less electron withdrawing than expected on the basis of their inductive (through-space) effect because of the intervention of an electron-releasing effect due to favorable through bond n(C0) u(C,C) p(C’) and n(C=NH) o(C,C) p(C+) interactions, r e s p e c t i ~ e l y . ~ ~
- -
-
~
~~
-
~
(25)For n-acylcarbenium ions, see: BBgu6, J. P.; Charpentier-Morize, M.; Pardo, C.; Sansoulet, J. Tetrahedron 1978,34,293-298. BBgu6, J. P.; Charpentier-Morize, M. Acc. Chem. Res. 1980, 13,207-212. Paddon-Row, M. N.; Houk, K. N.; Tidwell, T. T. Tetrahedron Lett. 1982,23, 383-386. See also: Hojo, M.; Masuda, R.; Ichi, T.; Yoshinaga, K.; Yanada, M. Tetrahedron Lett. 1982,23,4963-4964. Endo, Y.; Shudo, K.; Okamoto, T. J . Am. Chem. Soc. 1982,104,6393-6397.Olah, G. A.;Prakash, G. K. S.;Arvanaghi, M.; Krishnamurthy, V. V.; Narang, S. C. Ibid. 1984, 106, 2378-2380. Gassman, P. G.;Tidwell, T. T. Acc. Chem. Res. 1983, 16, 279-285. Creary, X.;McDonald, S. R.; Eggers, M. D. Tetrahedron 1981, 103, Lett. 1985, 26, 811-814. Creary, X. J . Am. Chem. SOC. 2463-2465. Creary, X.;Geiger, C. C. Ibid. 1982,104,4151-4162;1983,105, 7123-7129. Kulkarni, G. C.; Karmarkar, S. N.; Kelkon, S.L.; Wadia, M. S. Tetrahedron 1988,44,5189-5198.
This phenomenon is predicted to be less important in 3-(2)-iminobicyclo[2.2.21cation ( 17).
Acknowledgment. We are grateful to the Swiss National Science Foundation, the Fonds Herbette (Lausanne), and Hoffmann-La Roche and Co., AG (Basel) for financial support. We thank the Ecole Polytechnique FBd6rale of Lausanne (EPFL, CRAY 2 computer), the Swiss Institute of Technology in Zurich (ETHZ, CRAY XMP computer), and Prof. G. Bodenhausen, University of Lausanne (SUN 41, for generous gifts of computing time. Registry No. 11,22907-76-2; 12, 129314-99-4; 13, 129315-04-4; 14, 129315-00-0; 15, 129315-05-5;16, 129315-01-1; 17,129315-06-6; 18, 129315-02-2; 19, 129315-07-7;20,129315-03-3; 21,129315-08-8; 22, 129315-09-9;23, 129447-11-6;24,129315-10-2; 25,129447-12-7; 26, 280-33-1; 27, 2716-23-6; 28, 129315-11-3; 29, 129315-12-4; 30, 2972-20-5; 31, 129315-13-5; 32, 6962-74-9; 33, 5437-58-1; H-, 12184-88-2.
Supplementary Material Available: Atomic coordinates, bond lengths, and bond angles calculated (completely optimized geometries) by the AM1 method for 11-36 and by the STO 3G techniques for 11-19,26-30 (81 pages). Ordering information is given on any current masthead page.
Amino Alcohol and Amino Sugar Synthesis by Benzoylcarbamate Cyclization Spencer Knapp,* Paivi J. Kukkola, Shashi Sharma, T. G. Murali Dhar, and Andrew B. J. Naughton Department of Chemistry, Rutgers-The State University of N e w Jersey, N e w Brunswick, N e w Jersey 08903 Received A p r i l 10, I990
The sodium anion (3) of an alcohol-derived benzoylcarbamate (2) may be used to deliver an amino nitrogen intramolecularly to electrophilic carbon centers such as bromides, epoxides, and triflates, giving rise to amino alcohol and amino diol derivatives of general form 4-6. A procedure for selective monotriflation of carbohydrate diols is described that exploits the enhanced reactivity of carbohydrate hydroxyls flanked by a cis, vicinal ether oxygen. Subsequent benzoylcarbamate formation and cyclization allows the conversion of several sugars to amino sugars (47, 54, 74, 80). However, the cyclization occurs on the carbonyl oxygen if the triflate site is hindered (63 and 67). For the synthesis of amino compounds, intramolecular delivery of a nitrogen nucleophile sometimes offers advantages over the intermolecular variant. An extensive family of cyclization methods has been developed that allows the synthesis of amino compounds with excellent control over the position and the stereochemistry of the amino group, while minimizing the extent of competing elimination or rearrangement side reactions.’,* We recently introduced? coincidentally with McCombie’s group: the benzoylcarbamate cyclization method for the synthesis of amino alcohol and amino diol derivatives from precursors bearing a hydroxy group and a nearby electrophilic carbon center. In this paper we present the full description (1)Harding, K.E. In Comprehemiue Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, in press; Vol. 4, Part 1, Chapter 9. (2)Cardillo, G.; Orena, M. Tetrahedron 1990,46, 3321. (3)Knapp, S.;Kukkola, P. J.; Sharma, S.; Pietranico, S. Tetrahedron Lett. 1987,28, 5399. (4) McCombie, S.W.; Nagabhushan, T. L. Tetrahedron Lett. 1987,28, 5395.
0022-3263/90/1955-5700$02.50/0
and experimental details for these transformations and also describe their further application to the preparation of amino sugars. The concept of an alcohol-derived benzoylcarbamate 2 as a likely intramolecular source of nucleophilic nitrogen arose because [ l ] such derivatives should readily form under neutral conditions (1 2),5 [2] the anion 3 of a benzoylcarbamate should be easily generated and stable but still possess toward reversion to the original al~ohol,6-~ sufficient negative charge a t nitrogen to undergo N -
-
Ulrlch, ( 5 ) (a) H.Speziale, Chem, Reu. A. J.; 1965, Smith, 65, L. 369. R. J. Org. Chem. 1961,27,3742. (b) (6) The difference in acidity between a secondary alcohol (pK, = 16.5) and the alcohol-derived benzoylcarbamate (2) in water may be estimated a t about 7 pK, units, based on the pK.’s of ethyl acetoacetate (11) and phthalimide (9.9),and the roughly hundredfold greater acidity of amide N-H relative to ketone C-H. Lange’s Handbook of Chemistry; Dean, J. A., Ed.; McGraw-Hill: New York, 1972. March, J. Aduanced Organic Chemistry, 3rd ed.; Wiley-Interscience: New York, 1985;p 221. (7)For a review of the properties and chemistry of imidic compounds, see: Wheeler, 0. H., Rosado, 0. In The Chemistry of Amides; Zabicky, J., Ed.; Wiley Interscience: New York, 1970;pp 335-382.
0 1990 American Chemical Society
J. Org. Chem., Vol. 55, No. 22, 1990 5701
Benzoylcarbamate Cyclization
tion. Benzoylcarbamate derivatives of cyclohexene chlorohydrin and iodohydrin gave much lower yields of cyclized product compared with bromohydrin derivative 8. Selective removal of the benzoyl groups of the cyclized products (e.g., 9 10) was accomplished by treatment with lithium hydroxide in aqueous tetrahydrofuran! For all the N-benzoyloxazolidinones examined, lithium hydroxide promoted hydrolysis occurred preferentially at the benzoyl carbonyl group. However, the balance is shifted by substitution on the phenyl ring. For example, the p-(methoxybenzoy1)oxazolidinone19, formed in 65% yield
Scheme I'
6
7
-
P
19
18. R
H
i
'Reagents: (a) NBS, H 2 0 , 0 to 25 "C; (b) PhCONCO, CCI,, 25 'C; ( c ) NaH (1.25 equiv), THF, reflux; (d) LiOH, H,O. THF,25 "C.
cyclization,8 and [3] oneg or bothlo carbonyl groups of the cyclized product 4 should be removable from the amino nitrogen hy a basic hydrolysis step (4 5 6). These expectations have been generally fulfilled in practice, and for certain classes of amino alcohol derivatives, the benzoylcarbamate cyclization serves as an efficient synthetic method:".'J1
--
.
5
6
Cis-oxyamination of Alkenes. Bromobydrins" derived from alkenes such as 7, l l , and 15 (Scheme I) are useful substrates for intramolecular nitrogen delivery. Each was converted to a benzoylcarbamate derivative (8, 12, and 16, respectively) in high yield by treatment with benzoyl isocyanate. Because this reaction occurs without the necessity for a basic catalyst, neither epoxide formation from the bromohydrins nor base-promoted destruction of the products interferes. Even the tertiary alcohol from 11 reacts rapidly a t room temperature. Diagnostic for the formation of the benzoylcarbamate are infrared stretches at about 3260 cm-' for the N-H and about 1760 and 1690 em-' for the two carbonyl groups. Cyclization of the benzoylcarbamates was carried out by using sodium bydride in refluxing tetrahydrofuran solution. For best yields and to minimize premature hydrolysis of the cyclized products, it is important to use freshly opened sodium hydride and to carefully exclude moisture from the reac(8)Barton,D. H. R.; Motherwell, W. B. J. Chem. Soc., Perkin Tram. I 1980, 1124. See: Sammes, P. G.;Thetford, D. Chem. SOL, Perkin
T
r
~ 1989,655. ~ ~ ~ . (9) Evans, D. A,; Chapman, K. T.; Bisaha, J. J. Am. Chem. Soe. 1987.
,no f o e ? , w a , YO-'.
(10)Knapp. S.; Patel. D. V. J. Am. Chem. Soe. 1983,105.6985. (11) Jung, M. E.; Jung, Y. H. Tetrahedron Lett. 1989,30,6637. (12) (a) Dalton, D. R.; Dutta, V. P.; Jones, D. C. J. Am. Chem. Soe. 1968, 90. 5498. (b) Sisti, A. J. J. Oig. Chem. 1970, 35, 2670.
20
by analogous use of p-methoxyhenzoyl isocyanate, underwent nonselective hydrolysis to give a 2 1 mixture of oxazolidinone 10 and the hydroxy amide 20. Thus electron-donating substituents on the benzoyl group are probably to he avoided (we have also eschewed electronwithdrawing groups on the phenyl ring so as not to reduce the reactivity of the benzoylcarbamate anion). For convenience of isolation and characterization, the hydrolysis of the cyclized products was only taken as far as the oxazolidinones 10, 14, and 18, respectively, although more vigorous conditions, described below, convert the oxazolidinone to the free amino alcohol when this is desired. The conversion of cyclic alkenes to oxazolidinones such as 10, 14, and 18 amounts to an overall cis-oxyamination and as such compares favorably with other alkene cisoxyamination pro~edures'~J.'such as osmium-based methods15 and the iodine isocyanate method.I6 A useful aspect of the benzoylcarbamate cyclization method is that the face selectivity and site selectivity follow from those of bromobydrin formation, and bromohydrins may be formed in several waysL7with complementary selectivities, including water attack on a bromonium ion (Markovnikov addition, hydroxyl on more hindered face), epoxide cleavage by bromide anion by trans-diaxial attack (bydroxyl on less hindered face), and epoxide cleavage by bromide anion a t less substituted side (formal Markovnikov addition, hydroxyl on less hindered face). Synthesis of Amino Diol Derivatives. The use of epoxy alcohols as substrates for benzoylcarbamate cyclization should lead to amino diol derivatives, wherein the original epoxide stereochemistry dictates the stereochemistry of the product.3~.'J1 Many epoxy alcohols are available as nearly pure enantiomers when prepared by Sharpless epoxidation'8 of the corresponding allylic alcohols. Additionally, many allylic alcohols can be kinetically resolved by selective epoxidation of one e n a n t i ~ m e r or ' ~ obtained in homochiral form in other ways.2O Methods for the (13) Review of alkene oxyamination: Gasc, M. B.; Lattes, A,; Perie,
J. J. Tetrahedron 1983.39, 703.
(14) For a related method using benzyleabmates, see: Das, J. Synth. Cammun. 1988.18.907. (15) Harranz. E.:. Shamless. . . K. B. Ore. ISvnth. . 1983.61.85 . . and 93. and r e f & e k thekin. (16) Hassner, A.; Lorher, M. E.; Heathcwk. C. J. Orc. Chem. 1966,31, 540 and references therein. (17) For a compilation of references on bromohydrin formation, see: h m k . R. C . Comwehensiue Oreonic Tmnsformotions;VHC Publishers: New Yorlt; 1989; 326. (18) Can, Y.; Hanson, R. M.; Klunder, J. M.; KO.S. Y.; Masmune, H.; Sharpless, K. B. J. Am. Chem. Soe. 1987, 109, 5765 and references therein. (19) Martin, V. S.; Wwdward, S. S.; Kabuki, T.; Yamada, Y.: Ikeda, M.; Sharpless, K. B. J. Am. Chem. Soc. 1981, 103,6327. (20) See, for example: Satoh. T.; Oohara, T.;Ueda. Y.: Yamakawa, K. J. Oq.Chem. 1989,54. 3130 and references therein.
Knapp et al.
5702 J . Org. Chem., Vol. 55, No. 22, 1990 Scheme 111
Scheme 11" 0
am
H
41 21
23
22
42, R'=TI, R'=H
141-42)
44
43, R'=R2=Tf
24 1 LiOH,aqTHF
1 25 equiv NaH
0
n
THF, 0 OC OMe
85% (44 -345) 25
27
26
n
0
0
30
31
47
45, R=COPh 46, R=H
drolysis. The oxazolidinone product as its 0-acetate 36 matches the known compound.z6 0
28
29
"Reagents: (a) PhCONCO, CCld, 25 "C; (b) MCPBA, CH&, 25 "C; (c) NaH (0.25 equiv), THF, reflux; (d) LiOH, HzO, THF, 25 "C.
synthesis of 2-amino 1,3-diols are of continuing interest because this (or a closely related) functional array appears in sphingolipids, amino sugars, amino cyclitols, antibiotics, alkaloids, and amino acids.21,22 Three (racemic) isomeric epoxy carbamates 22,26, and 29 were prepared from cinnamyl alcohol (21) and phenylvinylcarbinol (25), and treated with 0.25 equiv of sodium hydride in refluxing tetrahydrofuran to effect cyclization (Scheme 11). The major product9 produced (23, 27, and 30) are isomeric oxazolidinone esters, wherein cyclization has taken place with the expected inversion in stereochemistry at the epoxide carbon closer to the carbamate nitrogen. In all three products, the benzoyl group has migrated from the nitrogen of the oxazolidinone to the newly formed hydroxyl, as evidenced by the carbonyl stretches at about 1750 and 1725 cm-' (compare 9 at 1780 and 1675 cm-') and the oxazolidinone N-H resonance at about 6.6 ppm in the 'H NMR spectrum. The cis-disubstituted oxazolidinone 27 shows a larger H-4/H-5 coupling constant (8 Hz) than the corresponding trans-disubstituted isomer 30 (6 Hz), corroborating the structure a ~ s i g n m e n t . ~ ~ Hydrolysis of the ester group in 23 and 27 led to the same monosubstituted oxazolidinone 22, whereas hydrolysis of 28 led to an isomeric product, the trans-disubstituted oxazolidinone 31. The benzylic methine at 5.39 ppm (d, J = 6) of 31 is diagnostic, whereas 24 lacks a doublet in this region. Evidently the cis-disubstituted isomer, which would have been expected as the initial hydrolysis product from 27 and which might experience steric repulsion between the 4-and 5-substituents, rearranged to 24 under the basic reaction conditions. An example relevent to aminocyclitol synthesisz5is the efficient conversion of epoxycyclohexanol32 to its carbamate 33 and then cyclization of 33 to 34 and partial hy(21) Jacobsen, S. Acta Chem. Scand. 1988, B42, 605. (22) Some recent examples: (a) Roush, W. R.; Brown, R. J. J . Org. Chem. 1982,47,1371. (b) Roush, W. R.; Adam, M. A. J.Org. Chem. 1985, 50, 3752. (c) Minami, N.; KO,S. S.; Kishi, Y. J . Am. Chem. SOC.1982, 104,1109. (d) Bernet, B.; Vasella, A. Tetrahedron Lett. 1983,24,5491. (e) Julina, R.; Herzig, T.;Bernet, B.; Vasella, A. Helu. Chim. Acta 1986, 69, 368. .(? Knapp, S.; Lal, G. S.; Sahai, D.J. Org. Chem. 1986,51, 380. For additional examples, see refs 3, 4, 8, 11, 25, 26, and 28b. (23) Small amounts of non-oxazolidinone (by IR analysis) byproducts were formed in these cyclizations, but were not further characterized. (24) (a) Spassov, S. L.; Stefanovsky, J. N.; Kurtev, B. J.; Fodor, G. Chem. Ber. 1972, 205, 2462. (b) Futagawa, S.; Inui, T.; Shiba, T. Bull. Chem. SOC.Jpn. 1973, 46, 3308. (25) For example, see: Kuhlmeyer, R.; Seitz, B.; Weller, T.; Fritz, H.; Schwesinger,R.; Prinzbach, H. Chem. Eer. 1989,122,1729and references therein.
_.,
-
OlNHCOPh
PhCONCO
,,.s
1 NaH.THF reflux 2 LiOH. aq THF
9 7%
32
90% 1 3 3 1 35) 33
34, R'=COPh, R2=H 35, R'=H. R*=H 36. R'.H R~=AC
In comparison to benzoylcarbamate cyclizations that afford oxazolidinone products, the homologous six-membered cyclizations are much more difficult to achieve. Epoxy benzoylcarbamate 37 was prepared in the usual way from 3-buten-1-01, However, under reaction conditions that were successful for cyclizations of epoxy benzoylcarbamates such as 22, 37 gave starting material and benzamide but no cyclized product corresponding to 38 or an isomer. It is possible that reversion of 37 to 3,4epoxbuten-1-01 and benzoyl isocyanate (a source of benzamide) occurred instead.
38
37
not observed
A situation where the reversion to starting epoxy alcohol could be documented arose during our recently completed synthesis of l i n c o m y ~ i n . The ~ ~ galactose-derived epoxy alcohol 39 formed benzoylcarbamate derivative 40 despite the congested environment of the C-4 hydroxy group. Sodium hydride treatment of 40, however, returned 39 without the formation of any detectable cyclization product. Three factors may contribute to this failure to cyclize: delivery of a nucleophile to C-6 of this hindered octose is known27to be difficult, six-membered ring cyclizations of the sort desired are rare,21and steric repulsions may be relieved upon loss of benzoyl isocyanate from the anion of 40. Successful intramolecular delivery of nitrogen to C-6 of 39 was later accomplished in a different manner, by employing the isourea anion generated from 39, sodium hydride, and N,N-dimethyl~yanamide.~~ Whether this latter method enjoys the generality of the benzoylcarbamate cyclization for other substrates has not yet been established. BnO H&
PhCONCO
Brio OMe 39
*& +N H oichp
NaH, THF, reflux-
BnO
39
Brio OMe 40
Amino Sugar Synthesis. Many amino sugars are synthesized by displacement reactions of carbohydrate derivatives such as p-toluenesulfonates,z8or, better, tri(26) Knapp, S.; Patel, D.V. J. Org. Chem. 1984, 49, 5072. (27) Knapp, S.; Kukkola, P. J. J. Org. Chem. 1990, 55, 1632
J . Org. Chem., Vol. 55, No. 22, 1990 5703
Benzoylcarbamate Cyclization
Scheme V
Scheme IV Ph
Ph
Ph
n
-20 OC
57 (1 2%)
56 (36%)
55
96% 40
+ 2 3-di.Otr1flale58 (12%) + sm 55 (39%)
S
49 R'=H $T .I
148-49)
50 R'&.TI
51
Ph Ph
Ph 1 LIOH,aqTHF 2 aq NaOH reflux
1 25 q u i v NaH c
THF HMPA 0 %
81%
80%
(52-541
(5142)
Lo
ok OMe
H2N
0 52, R=COPh 53, R=H
59
€4(25% in mix)
61 (25% in mix)
62 (24%)
+ sin 59 (25%)
54
reaction with electrophiles at the C-3 With fluoromethanesulfonates (triflates).B Thus for application triflic anhydride under the conditions described above, 48 of the benzoylcarbamate cyclization method to amino sugar gave the 3-0-triflate 49 in excellent yield accompanied by synthesis, a series of carbohydrate diol monotriflates would a trace of the 2,3-di-O-triflate 50 (confirmed by indebe useful. These could in principle be prepared by sependent synthesis). Purified 49 was converted to the lective triflation of the corresponding diol. We therefore benzoylcarbamate 51 and cyclized as before. The resulting investigated the preparation and cyclization of some carN-benzoyloxazolidinone 52 was then hydrolyzed in two bohydrate substrates akin to 2, where "X" is an alcohol steps to the 3-aminogulose derivative 54. derived triflate. The site selectively exhibited toward triflic anhydride Procedures exist for the selective tosylation and acylaby 41 and 48 is lost upon switching to the alternate tion of carbohydrate diols such as methyl 4,6-0-(phenylanomers. Thus methyl 4,6-0-(phenylmethylene)-/3-~methylene)-a-D-glucopyranoside(41, Scheme III),3°b1but glucopyranoside (55) (Scheme V) gave a mixture consisting there is little information on selective t r i f l a t i ~ n .We ~ ~ find of 3-0-triflate 56, 2-0-triflate 57, 2,3-di-O-triflate 58 that under carefully defined conditions (1.15 equiv of triflic (confirmed by independent synthesis), and recovered anhydride, 2.0 equiv of pyridine, 0.05 M substrate in distarting material. Likewise, methyl 4,6-0-(phenylchloromethane, -20 "C), triflic anhydride exhibits even methylene)-a-D-galactopyranoside(59) gave a mixture of better selectivity for the C-2 hydroxyl of 41 than other 59-62. What is the cause of these remarkable changes in electrophiles [the actual electrophile is probably N-((trirelative reactivity? fluoromethyl)s~lfonyl)pyridinium~~]. Thus 41 was conPrevious workers studying other electrophiles have verted to a single diol monotriflate (42) (Scheme 111). The s u g g e ~ t e dthat ~ ~ ,hydrogen ~~ bonding of the proton on the only detectable byproduct was a small amount of the reacting hydroxyl to a cis, vicinal ether oxygen can enhance 2,3-di-O-triflate 43,33whose structure was confirmed by its reactivity relative to another hydroxy group (which is independent and quantitative synthesis from 41 using presumably less electron rich). Examination of the 'H excess triflic anhydride in pyridine solution. The posiNMR spectra of 41, 48, 55, and 59 at 400 MHz in deution(s) of triflation in pyranosides is clearly indicated in teriochloroform solution reveals that hydroxyl protons that the 'H NMR spectrum by the downfield shift (typically can (possibly) hydrogen bond to nearby cis, vicinal ether about 1.1 ppm to 6 -4.9) of the appropriate ring methine oxygens show a larger splitting than those that are not cis proton(s). Purified 42 was then converted to benzoyland vicinal to an ether oxygen. There is an apparent three carbamate derivative 44 in the usual way (the stability of bond coupling of about 9 Hz between the hydroxyl proton the carbohydrate triflate group to the acylation conditions and the ring methine proton a t C-2 of 41, C-3 of 48, and is noteworthy). Cyclization of 44 was carried out under both C-2 and C-3 of 59, even in the presence of water. The the previously defined protocol, but at 0 OC, and the Nremaining hydroxyl protons appear as narrow doublets benzoyloxazolidinone 45 was isolated in good yield. Hy(apparent J = 2 Hz). Decoupling experiments indicate drolysis of 45, carried out in two steps to characterize the which signals are due to C-2 hydroxyl protons and which intermediate oxazolidinone 46, gave the methyl 2-aminoare due to C-3 hydroxyl protons. Figure 1 shows the hy2-deoxymannopyranoside 47,34 completing the sugar to droxyl region for all four diols. Addition of 1 mol 5% of amino sugar transformation. pyridine to the NMR solution of 41 broadens slightly both Methyl 4,6-0-(phenylmethylene)-/3-~-galactopyranoside C-2 and C-3 hydroxyl resonances relative to reference. (48, Scheme IV) has shown modest to good selectivity for Selectivity is therefore correlated with structure and NMR spectra in these four examples (strongly coupled hydroxyl groups, cis and vicinal to an ether oxygen, react (28) (a) Horton, D.;Wander, J. D.In The Carbohydrates: Chemistry and Biochemistry, 2nd ed.; Pigman, W., Horton, D., Eds.; Academic in preference to weakly coupled ones, not cis and vicinal Press: New York, 1980; Vol IB, pp 644-760. (b) Cerny, I.; Trnka, T.; to an ether oxygen), although hydrogen bonding is not Cerny, M. Collect. Czech. Chem. Commun. 1983, 48, 2386. thereby indicated to be causal.30 Rapid "trapping" of the (29) Karpiesiuk, W.; Banaazek, A.; Zamojski, A. Carbohydr. Res. 1989, 186, 156. product of initial sulfonylation by intramolecular removal (30) Haines, A. H. Adu. Carbohydr. Chem. Biochem. 1976, 33, 11. of the hydroxyl proton by the cis, vicinal ether o ~ y g e n ~ ~ , ~ (31) (a) Garegg, P. J.; Iverson, T.;Oscarson, S. Carbohydr. Res. 1977, would also explain the observed selectivities. Another 53, C5. (b) Box, L. L.; Box, V. G. S.;Roberts, E. V. E. Carbohydr. Res. 1979, 69, C1. is that lone-pair repulsion between the ether oxygen (32) (a) Binkley, R. W.; Ambrose, M. G. J. Carbohydr. Chem. 1984, and the hydroxyl oxygen might enhance the reactivity of 3, 1. (b) Binkley, R. W.; Abdulaziz, M. A. J. Org. Chem. 1987,52,4713. (c) Kunz, H.; Gunther, W. Angeur. Chem., Int. Ed. Engl. 1988,27,1086. (33) Englebrecht, G.J.; Holzapfel, C. W.; Verdoorn, G. H. S. Afr. J. Chem. 1989, 42, 123. (34) Bukhari, S. T. K.; Guthrie, R. D.; Scott, A. I.; Wrixon, A. D. Tetrahedron 1970, 26, 3653.
~~~~
~
~
(35) Kondo, Y. Carbohydr. Res. 1987, 162, 159. (36) Jencks, W. P. Acc. Chem. Res. 1976, 9, 425. (37) Box, V. G. S. Heterocycles 1983,20,677 and references therein.
5704 J . Org. Chem., Vol. 55, No. 22, 1990
Knapp et al.
1
I
n
I
80
Figure 1. 'H NMR spectra showing the hydroxyl region for the four carbohydrate diols 41,48,55, and 59, each -0.05 M in CDC13. Assignments and apparent coupling constants J are listed near the respective absorbances.
the latter. Explanations based on steric hindrance30or on the electronic withdrawing effect of the anomeric center,% may be declared unlikely, since relative reactivity does not correlate with either property. Migration or equilibration of the (trifluoromethy1)sulfonyl probably does not occur, since (for example) 42 and 49 are observed to be stable to the triflation, workup, and chromatography conditions. "Delivery" of the electrophile by the neighboring ether oxygen39might be possible for a positively charged electrophile in certain cases but seems unlikely for a neutral electrophile like benzoyl isocyanate (see below). We have also found that for furanosides and other carbohydrate substrates there is correlation of enhanced hydroxyl reactivity with the presence of a cis, vicinal heteroatom, although the other carbohydrate diols do not show quite the pronounced changes in relative hydroxyl reactivity exhibited by the pyranose substrates 41,48,55, and 59.40 Further investigation into this aspect of hydroxyl reactivity is currently underway. The greater reactivity of the 2-hydroxyl of 41 is retained with benzoyl isocyanate as the electrophile (suggesting that the selectivity may be an intrinsic property of the substrate and not depend strongly on the nature of the electrophile30). Thus condensation of 41 with benzoyl isocyanate under the usual conditions (Scheme VI) gave a 2:l mixture of the 2-0-carbamate and the 2,3-di-O-carbamate (no 30-carbamate was observed), and this mixture was treated (38) Dejter-Juszynski, M.; Flowers, H. M. Carbohydr. Res. 1973,28, 61. (39) (a) Knoblich, J. M.; Sugihara, J. M.; Yamazaki, T. J. Org. Chem. 1971,36,3407. (b) Chamberlin, A. R.; Mulholland, R. L.; Kahn, S. D.; Hehre, W. J. J. Am. Chem. SOC.1987, 109,672. (40) Knapp, S.; Naughton, A. B. J.; Kukkola, P. J.; Shieh, W.-C. Un-
published results. For a mechanistic study of the reaction of an intramolecularly hydrogen-bonded primary carbohydrate alcohol with phenyl isocyanate, see: Knapp, S.; Schreck, R. P.; Carignan, Y. P. Carbohydr. Res. In press.
Scheme VI 1 PhCONCO
''X+
2 TI20 CHSb pyr.
41
1 25equiv NaH
PhCONH*
66%
0
OMe
THF, 0 OC
63
P h T o O N
1 Lion, aq THF 2 aq NaOH reilux
PhToO%
+
Od
OMe NCOPh
0~
OMe
95% overalI from 9
6
64
66
65
Scheme VI1 Ph
L, \-u
1 PhCONCO 2 T120. pvr CH&
48
1 25 equlv NaH c
L
0 d oO&&OM TeI 0
66%
THF O°C
NHCOPh 67
Ph PhCON m
Ph
c-oy
0 O 68
M
e
+
60 01
=OMe
1 LiOH aqTHF 2 aq NaOH reflux
95% overall from ;6 69
b0 HO 70
with triflic anhydride to give the cyclization substrate 63. However, 63 underwent 0-cyclization, not N-cyclization, upon treatment with sodium hydride, giving a mixture of the benzoyl-iminocarbonate 64 and the allopyranoside cyclic carbonate 65.*l Lithium hydroxide converted the mixture entirely to 65, and more vigorous basic hydrolysis gave the allopyranoside 66.42 This reveals another avenue of reactivity available to benzoylcarbamates, the most (41) Copeland, C.; Stick, R. V. Aust. J. Chem. 1982, 35, 581. (42) Kondo, Y. Carbohydr. Res. 1973, 30, 386.
Benzoylcarbamate Cyclization
J . Org. Chem., Vol. 55, No. 22, 1990 5705 Scheme IX
Scheme VI11 1 6 eouiv T L O
0
3 2 equw 2 6 lulldine CH~CII 50
55
20°C
i
*
56
65%
--
PhCONCO
M oeO +O -+-hp
1 PhCONCOCH2C12
TI0
0
PhCOO T , o ~ ~ N H c o pNaH, h THF, rt. 6 h PhCOO
PhCONH
