J. Org. Chem. 1982,47,935-940
935
acetate mixtures, 101 and 51, respectively) were identical with those of an authentic sample provided by Wa~serman.'~The reaction mixture was fiitered through Celite, poured into pentane (15 mL), and washed three times with water (5 mL), and the material from the dried pentane solution was purified by preparative layer chromatography with ethyl acetate petroleum ether (15). The pheromone 5 was eluted with pentane and the solvent removed by passing a gentle stream of nitrogen over the solution. The infrared spectrum of the material obtained (130 mg, 64%) and that of the authentic sample15of the racemic 1were identical in the "fingerprint" region; []."D +81.5' (lit." +84.1°).
was added, and the solution was heated to reflux. After 2 h the reaction was complete, judging by the formation of an intensely absorbing product on TLC viewed by UV light. The reaction mixture was cooled in a water bath to room temperature and most of the solvent removed on a rotary evaporator. The reaction mixture was redissolved immediately in absolute ethanol and hydrogenated for 30 min with excess Raney nickel (1 g) as a catalyst. The hydrogenated product was then purified by column chromatography with benzene-diethyl ether (l:l),yielding 400 mg of synlpy 12 (65%) which exhibited the following data: TLC R , 0.37 [benzene-diethyl ether (1:1)]; [CYD ]' -3.2' (c 3.7, chloroform); IR 3450 (s, br), 2950 (s), 2880 (s), 1720 (e, sh), 1455, 1360, 730 (s), 690 (s) cm-'; NMR (220 MHz) 6 0.95 (t, 3, CHzCH3), OH),3.27 1.361.82 (m,6),2.09 (s, 3,COCH3),2.41(m,3,CH2C0, (m, 1, H-6) 3.45 (m, 1, H-7), 4.47 (d of AB q, 1,J A , B = 11.0 Hz, OCHAHBPh), 4.61 (d of AB 9, 1,JA,B = 11.0 Hz, OCHAHBPh), 7.35 (8, 5, OCH,Ph); mass spectrum, m / e 205 (M' + 1 CH&OCHJ, 115 (M' - CH3COCH3 - PhCH2). (1R ,5S,7R)-7-Ethyl-bethyl-l6,8-dioxabicyclo[ S%.l]octane [(+)-exo-Brevicomin (7)]. The ketone 12 (350 mg, 1.33 mmol) was dissolved in absolute ethanol (10 mL) and hydrogenated over a catalytic amount of palladium (5% on carbon). After 36 h, TLC indicated a faster running non-UV-active material had formed. The TLC mobilities ( R f0.51 and 0.57 in petroleum ether-ethyl
Acknowledgment. The work was supported by grants from the National Research Council of Canada and T h e Canadian Forestry Service (Environment Canada). We are deeply indebted t o Dr. Iain Weatherston (then at the Insect Pathology Research Institute) for numerous helpful discussions. Registry No. (+)-l, 20290-99-7; 4, 80485-56-9;7a, 582-52-5;7b, 18685-18-2; 7c, 22529-61-9; 7d, 22331-19-7; 8, 19877-13-5; a-ga, 80485-57-0; @9c, 80485-58-1; 80502-02-9; P-9a, 80502-03-0; CY-Qc, CY-9d, 80502-04-1;j3-9d, 80502-05-2;98,8048559-2; 11,80485-60-5;12, 80502-06-3.
Synthetic Routes to 6,8-Dioxabicyclo[3.2.1]octyl Pheromones from D-Glucose Derivatives. 3.t Synthesis of (-)-Frontalin Slawomir Jarosz, David R. Hicks, and Bert Fraser-Reid* Chemistry Department, University of Waterloo, Guelph- Waterloo Centre for Graduate Work in Chemistry, Waterloo, Ontario, Canada N2L3Gl Received June 24.1981
3-Deoxy-2-oxo glycosides with and without a C4 hydroxyl group are readily prepared from methyl CY-Dglucopyranoside. Reaction with methylmagnesium iodide gives the C2 tertiary alcohol with an axially oriented methyl group. The epimeric tertiary alcohol can be obtained by methylenation of the ketone followed by oxymercuration-demercuration.The carbinol obtained by the latter route has been converted into (-)-frontalin, the major naturally occurring enantiomer of the pheromone, by a sequence which can also be applied to obtain the (+) enantiomer. The preferred route utilizes the 3,4-dideoxyprecursor by benzylating the C2 tertiary alcohol and then hydrolyzing and reducing the anomeric center. The C5-C6 diol is then cleaved with periodate, and Upon hydrogenolysis a Wittig condensation affords 1,3,4,5-tetradeoxy-6-O-benzyl-6-C-methyl-~-glycero-hex~~e. of the benzyl ether, cyclization to frontalin occurs spontaneously.
In the preceding paper' we described a synthesis of exo-brevicomin for which the starting material was commercially available,2 1,2:5,6-di-O-isopropylidene-a-~glucofuranose ("diacetone glucose"). In an earlier communication from this laboratmy? we described some of our studies on the preparation of frontalin (1) from readily obtained (commercially available2) derivatives of methyl a-Pglucopyranoside, and in this paper we give full details of this work. Frontalin (1) was isolated4 as a component of the aggregation pheromone of Dendroctonus frontalis, and by synthesizing both enantiomers, Mori5 showed that the biologically active species was the 1S,5R form 1, having [ a I B D -52'. In addition, the molecule has been synthesized in racemiq6 both e n a n t i ~ m e r i c , 'a~n d unnatural ( lb)7b9c
* Present addresses: S.J., Institute of Organic Chemistry, Polish Academy of Sciences, Warsaw, Poland; D.R.H., Ayerst Laboratories, Montreal, Canada. B.F.-R., Chemistry Department, University of Maryland, College Park, MD 20742. 'For part 2 see ref 1. 0022-326318211947-0935$01.25/0
HO-C-CH,
==+ HO-C-CH,I
t CH3COCH=PPh3
forms, and notably in the context of of our work, Ohrui and Emoto have achieved a synthesis of the natural ma@ 1982 American Chemical Society
936 J. Org. Chem., Vol. 47, No. 6, 1982 terial (la)sbeginning with D-g1UCOSe by a totally different route from that reported herein. Although our primary interest was the naturally occuring enantiomer la, we were particularly interested in exploring routes which could be tailored to give one enantiomer or the other with only minor variations in the basic synthetic ~trategy.~ In keeping with our approach to exo-brevicomin,’ our target was the acyclic form of la, namely, 2 which is seen to have S chirality. This could be obtained from reaction of the tetrose 3 with the stabilized ylide 1-(triphenylphosphoranylidene)-2-propanone10(4) followed by hydrogenation. Thus our initial objective was to develop routes to the tetrose 3 and its mirror image. The primary requirement was therefore the preparation of the tertiary alcohol center(s) of 3 and its enantiomer in known configuration(s). For this task the readily prepared ketone 5” seemed a good starting point. The stereochemical outcome in additions to ketone 5 and the related olefin 8 were expected to be strongly influenced by the axial methoxyl group. Accordingly, Grignard addition to 5 (Scheme I) gave 6a as the exclusive product, while oxymercuration/demercuration was equally selective, giving 9a only. With methyllithium however, the reaction of 5 was much less specific, giving a 3:2 ratio of 6a and 9a. Although the structures of 6 and 9 follow from the method of their formation, we sought confirmation by spectroscopic methods. Lemieux12 and subsequently Li~ h t e n t h a l e r ’have ~ shown that for an epimeric pair of acetates on a pyranose ring, the methyl resonance of the axial member occurs to lower field in the ‘H NMR spectrum, Accordingly, the signal for 6b was at 6 2.01 and that for 9b at 6 2.08. The 13C NMR spectra gave independent support for these assignments. Thus the equatorial methyl group in 9 should be shielded by the methoxyl in accordance with the y effect;14 accordingly, the C2 methyl of 9a occurs at 20.93 ppm and that of 6a a t 23.1 ppm. The benzyl ethers 6c and 9c were hydrolyzed to give the diols 7 and 10 respectively, also crystalline materials. The lH NMR spectra of these diols provided independent confirmation for the structures assigned above on the basis of the shielding effects of geminal protons by neighboring oxygen function^.'^ Thus in 7 both the axial and equatorial protons a t C3 were coincident at 2.1 ppm; however, in 10 the equatorial H3 resonates a t virtually the same position, 2.2 ppm, while the axial H3 is considerably further upfield at 1.6 ppm. Evidently in 7 the C2 oxygen shields both C3 protons, while in 10 the C2 oxygen de(1) Sherk, A. E.; Fraser-Reid, B. J. Org. Chem., preceeding paper in this issue. (2) Pfanstiehl Laboratories, Waukengan, IL. (3) Hicks, D. R.; Fraser-Reid, B. J. Chem. Soc., Chem. Commun.1976, 870. (4) Kinzer, G. W.; Fentiman, A. F., Jr.; Page, T. F., Jr.; Faltz, R. L.; Vite.
