J. Org. Chem. 1987,52, 4851-4855 A similar experiment was carried out with (R)-(-)-octan-2-01 ~ (EtOH, c l . l O ) ] and a [182 mg, 1.40 mmol, Fluka; [ a ]-10.9" solution of DIS (2 mmol) in CHzClz(3 mL). This reaction was completed within 2 h at 27 "C, affording, after the usual workup, (S)-(+)-2-iodooctane (315 mg, 93%), ["ID +34.0° (ethanol, c 1.52) (approximately 57% optical purity). The above experiment with (R)-(-)-octan-2-01 and DIS was repeated as described (2 h at 27 "C). After completion, the reaction mixture was stirred at 17 'C for 3 days. The usual workup afforded (S)-(+)-2-idoodane(315mg, 93%), ["ID +30.8O (ethahol, c 1.98) (approximately 51% optical purity). B. With TMSI. A similar experiment was carried out with (S)-(+)-octan-2-01 (182 mg, 1.40 mmol) with TMSI (4 mmol) instead of DIS. The reaction was completed within 3 days at 17 "c,affording (R)-(-)-2-iodooctane (283 mg, 85%),28b[CY],,-49.4' (ethanol, c 1.44) (approximately 82% optical purity).
Acknowledgment. We thank the fellowship program (29)Buijs, W.; van Elburg, P.; Van der Gen, A. Synth. Commun. 1983, 13,387.
4851
of the Consent Nacional de Investigaciones Cientificas y Tecnicas de la Republica Argentina for their generous financial support. Registry No. PhSiH,, 694-53-1;PhSiHJ, 18139-86-1;SiHJ, 13598-42-0; SiHzIz, 13760-02-6; t-BuOH, 75-65-0; PhCH20H, 100-51-6;EtOH, 64-17-5; sec-BuOH, 78-92-2; i-PrOH, 67-63-0; PhCHz0CH2Ph,103-50-4;t-BuOMe, 1634-04-4;(i-Pr)20,10820-3; sec-BuOMe,6795-87-5; i-PrOMe, 598-53-8;i-PrOBu-n, 1860-27-1; n-BuOMe, 628-28-4; (Et)20, 60-29-7; (n-Bu)?O, 142-96-1; (nHex),O, 112-58-3;PhOMe, 100-66-3;PhOEt, 103-73-1;PhCH21, 620-05-3; t-BuI, 558-17-8; MeOH, 67-56-1; MeI, 74-88-4; I(CH2)4OH, 3210-08-0; I(CHJ41, 628-21-7; GPrI, 75-30-9; sec-BuI, 513-48-4; n-BuI, 542-69-8; n-BuOH, 71-36-3; EtI, 75-03-6; n-HexI, 638-45-9; @-naphthylOMe,93-04-9; ethyl acetate, 141-78-6;butane-1,3-diol, 107-88-0;3-iodobutan-1-01, 6089-13-0;5a,3@-cholestanol, 80-97-7; 3a-iodocholestane, 29108-97-2;3@-iodocholestane, (S)-octan-2-01,6169-06-8; 82863-87-4; (R)-octan-2-01,5978-70-1; (R)-2-iodooctane, 29117-48-4; (S)-2-iodooctane, 1809-04-7; @naphthyl alcohol, 135-19-3;phenol, 108-95-2;TMSI, 16029-98-4; THF, 109-99-9.
Oxidation of Vicinal Diols to a-Dicarbonyl Compounds by Trifluoroacetic Anhydride "Activated" Dimethyl Sulfoxide Catherine M. Amon, Martin G. Banwell,*l and G. Lance Gravatt Department of Chemistry, The University of Auckland, Private Bag, Auckland, New Zealand, and Department of Organic Chemistry, The University of Melbourne, Parkville, Victoria 3052, Australia Received March 12, 1987 Trifluoroacetic anhydride "activated" dimethyl sulfoxide is an effective oxidant for the conversion of vicinal diols into the corresponding a-dicarbonyl compounds or products derived therefrom. Unlike the Swern oxidant, the title reagent system gives good yields of products derived from halogenated substrates. The method has permitted syntheses of previously inaccessible compounds including tropolones, a u-homo-o-benzoquinone, and a "hyperreactive" a-keto aldehyde.
In connection with the development of a new route to tropolones, we observed2that the trifluoroacetic anhydride (TFAA)/dimethyl sulfoxide/ triethylamine (Et3N)reagent system3 efficiently (273% yield) converts various 7-halobicyclo[4.1.O]heptane-2,3- and -3,4-diols into the corresponding a-diketones. In contrast, the use2 of other oxidizing agents, many of which have been previously employed for converting vicinal diols into a-hydroxy ketones4b or a-diketones,@ led to decomposition of the bicyclic diols [with (Ph3P),RuC1,, benzalacetone, tetrahydrofuran (THF), 195 OC, 10 h8], low yields ( 1 2 5 % ) of the desired products (oxalyl chloride, dimethyl sulfoxide, Et3Ng),or no reaction (N-chlorosuccinimide,dimethyl sulfide, Et3N;4 (1)Please address any correspondence to this author a t the University of Melbourne. (2)Banwell, M. G.; Onrust, R. Tetrahedron Lett. 1985, 26, 4543. Onrust, R. M.S. Thesis, The University of Auckland, 1985. (3)For a review of activated dimethyl sulfoxide reagents see: Mancuso, A. J.; Swern, D. Synthesis 1981,165. (4) Corey, E. J.; Kim, C. U. Tetrahedron Lett. 1974,287. (5)Marshall, J. A.;Cohen, G. M. J. Org. Chem. 1971,36,877. (6)Newman, M. S.:David. C. C. J. Ow. Chem. 1967., 32., 66. Yates. P.; Lewars, E. G. J. Chem. SOC. D 1971,i537. (7)Goh, S.H.;Harvey, R. G. J. Am. Chem. SOC. 1973,95,242.Harvey, R. G.; Goh, S. H.; Cortez, C. J. Am. Chem. SOC. 1975,97,3468. (8) Regen, S. L.; Whitesides, G. M. J. Og. Chem. 1972, 37, 1832. (9)Ireland, R. E.; Norbeck, D. W. J. Org. Chem. 1985,50,2198.
acetic anhydride, dimethyl sulfoxide;6 pyridine, SO3, didimethyl methyl ~ u l f o x i d e dicyclohexylcarbodiimide, ;~~~ Other workers have noted13J6the insulfoxide, H+ ability of the last group of reagents to oxidize certain vicinal diols. In view of these results, and because no systematic assessment has been made of the ability of the TFAA "activated" dimethyl sulfoxide oxidant'l to effect the synthetically valuable vicinal diol to a-dicarbonyl conversion,l8a more extensive investigation of this reagent (10)Pfitzner, K.E.; Moffatt, J. G. J. Am. Chem. SOC. 1965,87,5661. have also been employed for the (11)Other oxidizing preparation of a-hydroxy ketones or a-diketones from vicinal diols. However, all of these employ reagents incompatible with the functionality present in our substrates and were, therefore, not investigated. Thus, both the bis(tributy1tin) oxide/BrJ2J3 and dimethyl s u l f ~ x i d e / C l ~ / E ~ N ~ ~ procedures are likely to effect undesired halogenation of unsaturated centers. The ability of Ag(1) ions to promote cleavage of halogenated cyclopropanes deterred us from using Ag,CO, on CeliteI5 as an oxidant. (12)Ueno, Y.; Okawaro, M. Tetrahedron Lett. 1976,4597.Del Nero, S.; Lombardi, P. Gazz. Chim. Ital. 1983,113,125. (13)Russell, R.A.; Kraus, A. S.; Irvine, R. W.; Warrener, R. N. Aust. J. Chem. 1985,38,179. (14)Corey, E. J.; Kim, C. U. Tetrahedron Lett. 1973,919. D 1969,1102. (15)Fetizon M.; Golfier, M.; Louis, J.-M. J.Chem. SOC. Fetizon, M.; Golfier, M. C. R. Seances Acad. Sci., Ser. C 1968,267,900. (16)Dailey, 0.D.; Fuchs, P. L. J. Org. Chem. 1980,45, 216. (17)T o our knowledge, only one example of the use of TFAA/dimethyl sulfoxide/Et3N for the oxidation of a vicinal diol has been reported.16
0022-3263/87/1952-4851$01.50/00 1987 American Chemical Society
A m o n et al.
4852 J . Org. Chem., Vol. 52, No. 22, 1987 Table I. Oxidation of Vicinal Diols by Trifluoroacetic Anhydride “Activated” Dimethyl Sulfoxide entrv 1
2
3 4
diol 1,2-dodecanediol (1)
oxidation product(s)” 2-hydroxy-2-dodecenal (12)
‘8iiOH 12)
0
Ho;,:G
trans-1,2-cyclohexanediol(3) cis-1,2-cyclohexanediol (4)
2-hydroxy-2-cyclohexen-1-one(14) 2-hydroxy-2-cyclohexen-1-one(14)
18)
5 6 m
8
113)
HO
-y&
115)
1,2-cyclooctanedione (16) 2J-octanedione (17) benzil (18)
cis-1,2-cyclooctanediol (6) erythro-2,3-octanediol (7) meso-1,2-diphenyl-l,2-ethanediol (8)
(19’
9
10 11
yield, 7hb 79
68 (25)/ 79
82 54 ( O Y 95‘ (91)f 87 98 (97)t 76 (25)f
85
5a-cholestane-2a,3a-diol (11)
T h e tautomeric preference in compound which predominated in deuteriochloroform otherwise stated. c This material contains e Yield after recrystallization of preparative oxide as the oxidant.
2-hydroxy-5a-cholest-l-en-3-one (21) and 3-hydroxy-5a-cholest-3-en-2-one (22)
84d 71‘
20 has not been determined. All other oxidation products are depicted in the tautomeric form, solution a t 18 O C as established by NMR analysis. *Of isolated and pure products unless some 4-(diethylamino)-l,l,l-trifluorobut-3-en-2-one. Yield after preparative TLC isolation. TLC material. f Yield of product obtained by using oxalyl chloride “activated” dimethyl sulf-
system seemed warranted. The results of such a study, which we now report, suggest that this oxidizing system is particularly well suited to the present purpose and allows the preparation of hitherto inaccessible a-dicarbonyl and related compounds. The tabulated data demonstrate that the title reagent system smoothly converts both open-chain and cycliclg vicinal diols into the corresponding a-dicarbonyl compounds or products derived therefrom. Noteworthy results include the formation of the “hyperrea~tive”~ a-keto aldehyde (isolated as its monoenolic tautomer 12) from diol 1 (Table I, entry 1) and the oxidation of compound 2 to the u-homo-o-benzoquinone 13 (entry 2). Product 13 is only the third example20 of this rare class of compound. The tropolones 19 and 20 (entries 9 and 10) are formed as a result of in situ ring expansion of the initially produced bicyclic diketones.2 Since several recent reportsz1 have stressed the useful biological activity of tropolones containing three or more contiguously oxygenated ring carbons, the synthesis of compound 20 is especially interesting. The oxidation procedure appears insensitive to the geometry of the hydroxyl groups in the starting diol since analogous treatment of the trans- and cis-diols 3 and 4 (18) For a discussion on the synthetic utility of a-dicarbonyl compounds, see: Sharpless, K. B.; Lauer, R. F.; Repic, 0.;Teranishi, A. Y.; Williams, D. R. J. Am. Chem. SOC.1971, 93, 3303. Wasserman, H. H.; Ives, J. L. J. Am. Chem. Soc. 1976, 98, 7868. (19) Attempts to convert exo,exo-bicyclo[2.2,l]heptane-2,3-diol into bicyclo[2.2.l]heptane-2,3-dioneby using this procedure gave widely varying yields (0-83%) of the diketone. These results are attributed to the instability of the oxidation product. See: Hanack, M.; Dolde, J. Justus Liebigs Ann. Chem. 1973, 1973, 1557. (20) The parent u-homo-o-benzoquinone is known; see: Engelhardt, M.; Luttke, W. Chem. Ber. 1977, 110, 3759. Sugihara, Y.; Yamoto, A.; Murata, I. Tetrahedron Lett. 1981,22, 3257. One functionalized derivative has been synthesized; see: Vol’eva, V. B.; Prokofeva, T. I.; Novikova, I. A.; Belostotskaya, I. S.; Ershov, V. V. Zzo. Akad. Nauk SSSR, Ser. Khim. 1984, 1632; Chem. Abstr. 1984, 101, 230384. (21) Kirst, H. A.; Marconi, G. G.; Counter, F. T.; Ensminger, P. W.; Jones, N. D.; Chaney, M. 0.;Toth, J. E.; Allen, N. E. J. Antibiot. 1982, 35, 1651. Takashi, S.; Takazawa, S.; Okaji, M.; Kawamoto, I.; Sato, T.; Oka, T.; Shirohata, K. Jpn. Kokai Tokkyo Koho 1978 78-135954; Chem. Abstr. 1979 90, 119757a. Kitamura, S.; Iida, T.; Shirahata, K.; Kase, H. J. Antibiot. 1986, 39, 589.
(entries 3 and 4) gave reaction product 14 in similar yields. In some instances, small quantities (58%) of 4-(diethylamino)-l,l,l-trifluorobut-3-en-2-one22 were observed in the crude oxidation mixtures. This material, which was easily separated from the desired a-dicarbonyl compounds by chromatography, probably arises by a single electron transfer initiated reaction of TFAA with Et3N.23 In a control experiment, treatment of the preformed dimethyl sulfoxide/TFAA complex (maintained at -60 “C in CH2Cl2, no diol present) with Et3N afforded a 33% yield of the acylated enamine. Presumably, complex formation between TFAA and dimethyl sulfoxide is reversible and, in the absence of an alcohol oxidation pathway, reaction between the anhydride and the amine becomes a significant process. Interestingly, entries 2, 5 and 9 (Table I) show that the oxalyl chloride ”activated” dimethyl sulfoxide system (Swern o x i d a t i ~ n )is~ ?a ~much less effective oxidant, a t least when the substrate contains a halogen atom. Why this is so remains unclear. In conclusion, the TFAA “activated” dimethyl sulfoxide reagent system provides an especially useful method for the oxidation of vicinal diols to a-dicarbonyl compounds. The procedure requires mild reaction conditions, gives high yields of product, is relatively general, and uses readily available reagents. Experimental Section General Procedures. ‘H N M R spectra were recorded o n a Varian T60 or JEOL FX-9OQ spectrometer and 13C N M R spectra o n a JEOL FX-60 or FX-9OQ instrument. Deuteriochloroform was used as solvent unless otherwise stated. Chemical shifts are reported as 6 values in p a r t s p e r million relative t o tetramethylsilane (6 0.0 p p m ) as an internal s t a n d a r d . Data are reported as follows: chemical shift (multiplicity, coupling constants, integrated intensity). Infrared spectra (IR) were recorded o n a Shimadzu IR-27G spectrometer. Electron-impact mass spectra (MS) a n d high-resolution mass spectra (HRMS) were measured (22) Platoshkin, A. M.; Cheburkov, Yu. A,; Knunyants, I. L. Izu. Akad. Nauk SSSR, Ser. Khim. 1969,112-119; Chem. Abstr. 1969, 70,114541. (23) Schreiber, S. L. Tetrahedron Lett. 1980, 21, 1027.
Oxidation of Vicinal Diols
J. Org. Chem., Vol. 52, No. 22, 1987 4853
on Varian MAT CH7 and AEI-MS3074 mass spectrometers, readditional phenol (270 mg, 29%). spectively. Ultraviolet spectra (W)were determined on a Varian A solution of compound 23 (160 mg, 0.49 mmol) in THF (5mL) DMS-100 instrument. Melting points were observed on a Reicwas treated with 3 M aqueous HCl (2.9 mL), and the resulting hert-Kofler block and are uncorrected. Microanalyses were mixture was allowed to stand at ambient temperatures for 55 h performed by Professor A. D. Campbell and associates a t the before being poured into water (30 mL) and extracted with EbO University of Otago, Dunedin, New Zealand, or by the Australian (3 X 5 mL) and then CH2C12(3 X 25 mL). The combined organic Microanalytical Service, Melbourne, Australia. Analytical thinphases were washed with water (50 mL), dried (MgS04),filtered, and concentrated under reduced pressure to give a pale yellow layer chromatography(TLC) was conducted on aluminum-backed oil (100 mg), which solidified on standing. 'H NMR, I3C NMR, 2-mm-thick silica gel 60 F254 p!ates supplied by Merck. Chromatograms were visualized with iodine vapor, anisaldehydeand TLC analyses of this material showed it to be a ca. 9 1 mixture /H2S04/EtOH (2593, v/v/v) spray reagent, or under a 254-nm of the required diol 2 and precursor 23. (This mixture was used UV lamp. Preparative TLC was conducted on 20 X 20 cm glass in the subsequent oxidation step.) Recrystallization (C6H6)of plates loaded with Merck Kieselgel60GFm (34 g/plate) or Reidel the solid mixture afforded spectroscopically pure 2 as off-white de Haen aluminum oxide DGF (400 mesh ASTM, 38 g/plate) crystalline masses: mp 83-85 "C; 'H NMR 6 5.95 (m, 2 H), 4.0 using the solvent system indicated. All extraction, recrystalli(m, 2 H), 2.80 (br s, 2 H, OH), 2.40 (dd, J = 6.5 and 2.5 Hz, 1 H), zation, and chromatographic solvents were distilled prior to use. 2.10 (dd, J = 6.5 and 3.5 Hz); 13CNMR 6 131.6,127.0,66.7,64.3, 35.2,33.7, 29.6; IR (KBr) 3375,1630 cm-'; MS, m/e 264 (2), 266 Dimethyl sulfoxide was distilled from CaH2 under reduced pressure. THF and diethyl ether (Et20) were distilled from (9), 268 (3) [[M - H,O]'+], 77 (100). benzophenone ketyl before use. Et3N was distilled from KOH (2a,3a,4a&8aB)-9,9-Dichloro-1,2,3,4,5,8-hexahydro-4a,8apellets and dichloromethane (CH2C12)from CaH2 Aldrich Gold methanonaphthalene-2,3-diol(5). A mixture of (4aa,8aa)Label TFAA and Fluka oxalyl chloride were used as obtained. 9,9-dichloro-l,4,5,8-tetrahydr0-4a,8a-methanonaphthalene~~ (1.20 All reactions requiring anhydrous conditions were run under an g, 5.58 mmol), tert-butyl alcohol (23 mL), water (6.8 mL), pyridine argon atmosphere in oven-dried glassware. (1.0 mL), and trimethylamine N-oxide dihydrate (1.38 g) was Diols 1,244,29 6,25 7,26 9: and 112' were perpared from the treated in one portion with osmium tetraoxide in tert-butyl alcohol corresponding olefins by using either the literature procedure or (0.46 mL of a 2.5 wt % solution, Aldrich), and the resulting the dihydroxylation method of Ray and Matteson.28 Diols 329 solution was heated at reflux under an argon atmosphere for 48 and 830were prepared from cyclohexene and benzil, respectively, h. The dark brown solution thus obtained was cooled, treated by using the cited procedures. All compounds had spectroscopic with sodium metabisulfte (20 mL of a 20 wt % aqueous solution), and physical properties in accord with those reported in the and then filtered and concentrated. The residue was partitioned literature. Compounds 2, 5, and 10 were synthesized by the between EhO (50 mL) and water (50 mL), and the resulting phasmethods detailed below. were separated. Extraction of the aqueous phase with EtzO (2 (lafa,3a,6a)-7,7-Dibromobicyclo[4.1.0]hept-4-ene-2,3-diol X 30 mL) and drying (MgSO,) of the combined organic phases (2). A 1.0 M solution of potassium tert-butoxide in tert-butyl followed by filtration and concentration afforded a light brown alcohol (20 mL) was added over a period of 4 h to a chilled (ice) solid. Recrystallization (CH2C12)of this material afforded diol solution of (la,6a)-8,8-dimethyl-7,9-dioxabicyclo[4.3.0]nona-2,4- 5 (0.95 g, 68%) as white needles: mp 117.5-118.5 "C; 'H NMR diene31(1.25 g, 8.22 mmol) in tert-butyl alcohol (5mL) containing 6 5.50 (m, 2 H), 3.75 (m, 2 H), 2.50-1.50 (complex m, 10 H); 13C bromoform (3.32 g, 13.15 mmol). The resulting mixture was stirred NMR (C5D5N)6 76.8, 68.4,36.9, 32.0,27.2 [the signal due to the a t ca. 5 "C for 1 h and then at ambient temperatures overnight vinylic carbons is obscured by the solvent resonances but is obbefore being poured into hexane (25 mL) and quenched with water served in CDC13at 6 122.851; IR (KBr) 3500,3425,3380,2900cm-'; (25 mL). The two phases were separated, and the aqueous phase MS, m/e 230 (21), 232 (12.5), 234 (1) [[M - H20]*+],91 (100) was extracted with hexane (25 mL). The combined organic phases [[C7H7]*+].Anal. Calcd for CllH14C1202:C, 53.03; H, 5.66; C1, were washed with water (3 X 30 mL), dried (MgS04), filtered, 28.46. Found: C, 53.05; H, 5.78; C1, 28.28. and concentrated under reduced pressure to give an oil. Prep(la,2a,3a,48,6a)-7,7-Dibrom0-4-met hoxybicyclo[ 4.1 .O] heparative TLC (silica gel, CH2C12)afforded two bands, A (Rf 0.6) 7,7-Dibromobicyclo[4.1.0]hept-3-ene34 (6.0 tane-2,3-diol ( and B (R, 0.5). Extraction (CH2C12)of band A afforded a solid, g, 23.8 mmol) was added to a stirred suspension of freshly rewhich on recrystallization (methanol) gave (3aa,5aD,6a@,6ba)crystallized N-bromosuccinimide (4.26 g, 24 mmol) in dried 6,6-dibromo-2,2-dimethyl-3a,6,6a,6b-tetrahydro-5~-cyclomethanol (12 mL). Following the slow addition of ca. 0.5 mL of propa[e]-1,3-benzodioxole(23)= (780 mg,29%) as white crystalline 98% H2SO4, the reaction mixture was allowed to stir at ambient masses: mp 80.5-82 "C; 'H NMR 6 5.90 (m, 2 H), 4.65 (br d, J temperatures for 48 h. The resulting deep yellow solution was = 7 Hz, 1 H), 4.40 (d of m, J = 7 Hz, 1 H), 2.35 (m, 2 H), 1.40 poured into water (100 mL) and extracted with CH2C12(3 X 25 (s,6 H); 13CNMR 6 128.0, 123.1, 109.4, 70.3,69.3,32.8, 29.9,28.2, mL). The combined organic phases were dried (MgS04),filtered, 27.6,25.8; IR (KBr) 2975,1370,1244,1210,1160,1040,1025,880, and concentrated under reduced pressure to give a yellow oil. 860,765,700 cm-'; MS, m/e 265 (4), 267 (9), 269 (3) [[M - H3CTrituration (methanol) of this material gave a white crystalline - CH2COl+l,43 (100) [[CH3COl+l.Anal. Calcd for Cl$lzBrz02: solid, recrystallization (methanol) of which afforded (la,3a,4@,6a)-3,7,7-tribromo-4-met hoxybicyclo[ 4.1 .O]heptane C, 37.07; H, 3.73; Br, 49.32. Found: C, 37.20; H, 3.92; Br, 49.48. Extraction (CH2Cl2/Et20)of band B afforded phenol (120 mg, (24)32(5.0 g, 58%) as white plates: mp 70.5-72 "C; 'H NMR 6 13%) identical by 'H NMR, IR, and TLC with an authentic 4.05 (q with further coupling, J = 8 Hz, 1H), 3.40 (s, 3 H), 3.25 sample. Acidification and then extraction (CH2C12)of the aqueous (m, 1 H), 2.65 (complex m, 3 H), 1.95 (complex m, 2 H), 1.34 phase obtained in the workup procedure detailed above gave (complex m, 1H); 13CNMR 6 79.3, 57.5, 50.6, 37.3,33.3, 28.8,27.0, 26.9; IR (KBr) 2870, 1430, 1127, 1098, 1040, 825, 746, 723, 622 cm-'; MS, m/e 328 (
