J. Org. Chem. 1993,58,6545-6547
6548
High-Precision Asymmetric Synthesis of Stegobiol and Stegobinone via Boronic Esters Donald S. Matteson' and Hon-Wah Man Department of Chemistry, Washington State University, Pullman, Washington 99164-4630 Received September 9, 1993.
Summary: Highly stereoselective boropic ester chemistry has been used to synthesize the drugstore beetle pheromones stegobiol and stegobinone. The convergent route utilizes a single intermediate containing all of the stereogenic centers for both segments of the pheromones, requires only one chromatographic separation, and is the first synthesis to provide pure, crystalline samples.
(2S,3R,l'S,Z'S)-Stegobiol(l)and (2S,3R,l'R)-stegobinone (2)are pheromones of the drugstore beetle Stegobium paniceum (Anobiidae),lS2an economically important pest of stored foodstuffs, and 2 is also the attractant of the furniture beetle, Anobiumpunctatum, a wood-eating pest.3 Stegobinone (2)has proved a particularly elusive synthetic target because it readily epimerizes, the 1'-epimer (3)is repellent to S. paniceum, and previous partially crystalline4or oily6 synthetic 2,which contained some 3 and other diastereomers, was unstable to prolonged storage. Synthetic racemate of 2 was also repellent, and samples of 2 at room temperature lost attractiveness in 2 weeks? The asymmetric chain extension of alkylboronic esters,' which with chiral directors of C2 symmetry has yielded diastereoselectivities >10001,8 is the key to the first pure, crystalline synthetic (2R,3R,l'S,2'S)-stegobiol(l) (mp 7374 "C (lit.29~il) and (2R,3R,l'R)-stegobinone (2)(mp51.552.5 "C; from natural source2mp 52.5-53.5 "C). Both the flexibility of the method and the precise stereocontrol, even though only 1OO:l at the critical labile stereogenic C(l'), were significant factors in the success of this approach. The only necessary chromatography in the entire synthetic sequence is for the final purification of 1.
-
ethanediol," available from Sharpless dihydroxylation of trans-stilbene12 and hydrogenation over rhodium.llJ3 Previously described procedures7were used for the reaction of 4 with (dichloromethy1)lithium to form chain-extended chloro boronic ester 5 and for the reaction of 5 with lithium benzyl oxide to form 6. Similar reaction of 6 with (dichloromethy1)lithiumfollowed by reaction of the chloro boronic ester (not illustrated) with methylmagnesium bromide yielded 7. A third chain extension, 7 with (dichloromethyl)lithium, yielded key intermediate 8. Deboronation of 8 to aldehyde 9 with hydrogen peroxide proved efficient at pH 9, in contrast to some previous oxidations of a-chloro boronic esters.14 Chromatography on silica partially epimerized 9,but bulb tobulb distillation yielded 9 containing 0.5-1 % (2R*,3S*)-epimerby 1H-NMR analysis, bp 94-95 "C (0.4 Torr), 65% from 4 without purification of any intermediate, except to obtain analytical samples.1° A second portion of 8 was treated with methylmagnesium bromide to furnish 10,which wasdeboronated with alkaline hydrogen peroxide to lla, which was distilled, tertbutyldimethylsilylated to 11b, debenzylated to 1 IC, and finally oxidized with pyridinium dichromate to 12,bp 41 "C (2 Torr), 28% based on 4. Ketone 12 is the second piece needed for the aldol condensation. In order to achieve debenzylation of llb without desilylation, it was necessary to use palladium hydroxide and calcium carbonate to suppress traces of acid from the silylation step. Conversionof 12to dibutylboron enolate 13 and reaction with aldehyde 9 was carried out by a literature method
Key intermediate chloro boronic ester 8 incorporates all of the stereogenic carbons of both intermediates 9 and 12, which are converted to 1 via convergent aldol condensation.1° Chiral boronic ester 4 was prepared from dibutyl ethylboronate and (1R,2R)-1,2-dicyclohexyl-
(10)The following were characterized by 3ocl-MHz 'H-NMR and 75MHz W-NMR, plus analysis or high-resolution maas spectra if indicat& [ 4 R - ( 4 0 , 5 ~ ) 1 - 4 , 5 - d i ~ ~ o h ~ 1 - 2 ~ 1 - 1 (4), , 3 ~HRMS ~oxa~~e (CuH&OZ), C, H, B 6, HRMS (Ci7HmOzBCl); [4R-[2(R*),4~~,5@11-2[l-(phenylmethoxy)propyl]-4,5-dicyclohexyl-l,3,2-dioxaborolane(6), HRMS (-Bod C d c d 74.00,found 74.78,H [4R-[2(1S',2@),4~,5fl]2-[l-chloro-2-(phenylmethoxy)butyll-4,5-dicyclohexyl-1,3,2-dioxaborolane (intermediate between 6 and 7), HRMS (C&&ClOa), 7; [a(2(1S*,2S*,3S*) ,4a,5@l] -2[l-chloro-2-methyl-3-(phenylmethoxy)pentyl] 4,5-dicyclohexyl-1,3,2-dioxaborolane (8), HRMS (Cn&BClOs); 9 HRMS (CisHieOz);10, HRMS (CzeHlsBOa),C, H, B 118 (ClrHnnOn), C, H; Ilb, HRMS-CI (CasTOnSi, M+ + 1); 12,reported previously;6 14,HRMS-CI Mt + 1);0-benzyl(C&4704Si, M+ + 1);16,HRMS-CI (C&O&i, stegobiol (16),HRMS ( C a a O a , Mt), calcd C, 75.91,H, 8.92,found C, 75.39,H,8.89;l,ClsHllOacalcdC,68.99,H,9.80,foundC,68.90;H,9.66,
Abstract published in Advance ACS Abstracts, October 15, 1993. (1)Kuwahara, Y.;Fukami, H.; Howard, R.; Ishii, S.; Mataumura, F.; Burkholder, W. E. Tetrahedron 1978,34, 1769-1774. (2)Kodama, H.; Ono, M.; Kohno, M.; Ohnishi, A. J. Chem. Ecol. 1987,
(11)Hoffmann,R. W.; Ditrich, K.; Kbster, G.; S t h e r , R. Chem. Ber. 1989,122,1783. (12)(a) Jacobsen, E. N.; Mark6, I.; Mungall, W. S.; Schrbder, G.; Sharpless, K. B. J.Am. Chem. SOC.1988,110,1968-1970.(b) Sharpleee, K.B.; Amberg, W.; Bennani, Y.L.; Criepino, G. A.; Hartung, J.; Jeong,
1
2
3
13,1871-1879. (3)White, P.R.; Birch, M. C. J. Chem. Ecol. 1987,13,1695-1706. (4)(a) Hoffmann, R. W.; Ladner, W.; Steinbach, K.; Massa, W.; Schmidt, R.;Snatzke, G. Chem.Ber. 1981,114,2766-2801.(b) Hoffmann, R. W.; Ladner, W. Tetrahedron Lett. 1979,4653-4656. (5)Mori, K.; Ebata, T. Tetrahedron 1986,42,4413-4420. (6)Kodama, H.; Mochiuki, K.; Kohno, M.; Ohnishi, k; Kuwahara, Y . J. Chem. Ecol. 1987,13,1869-1869. (7)(a) Matteeon, D. S.; Sadhu, K. M.; Peterson, M. L. J. Am. Chem. SOC.1986,108,812-819.(b) Matteeon, D. S. Chem. Rev. 1989,89,15351551. (c) Matteeon, D. 5.;Kandil, A. A.; Soundararajan, R J.Am. Chem. SOC. 1990,112,3964-3969. (8)Tripathy, P.B.; Matteson, D. S. Synthesis 1990,200-206. (9)Mori, K.; Ebata, T. Tetrahedron 1986,42,4685-4689.
2.
K.-S.; Kwong, H.-L.; Morikawa, K.; Wang,2.-M., Xu, D.; Wang, X.-L.
J. Org. Chem. 1992,57,2768-2771.
(13)(a) (R,R)-1,2-Diphenyl-l,2-ethanediol(50 g) was hydrogenated at
1 atm over 5% Rh/AlzOs (2g) in methanol (so0mL) containing 1%water and 1% acetic acid over a period of a few days. Diphenylethanediol
should be washed with aqueous sulfuric acid to remove traces of alkaloidal catalyst poison before hydrogenation. One batch from the new procedurelzb appeared to contain a catalyst poison that could not be removed, another did not. We thank Dr. G. D. Schaumberg, Sonoma State University, for developing the hydrogenation conditions. (b) Diphenylethanediol is not a satisfactory chiral director," a finding that has been replicated by G. D. Schaumberg. (14)Brown, H.C.; Imai, T.; Deaai, M. C.; Singaram, B. J.Am. Chem. SOC.1986,107,4980.
0022-3263/93/1958-6545$04.00/00 1993 American Chemical Society
6646
J. Org. Chem., Vol. 58, No. 24, 1993
Communications
Scheme 1.
I W
4
5
BnO
BnO
CI
:
l
'
PPm
. . 1
'
l
2.8
'
I
2.7
'
I
2.6
.
I
2.5
'
Figure 1. Portion of the 300-MHz 'H-NMR spectrum of [S-(2R*,3R*)1-2-methyl-3-(phenylmethoxy)pen~ (9). (a) U p per curve: magnified, showing -0.5% [R-(2R*,3S*)]-epimer at ii 2.58, flanked by lSC satellites of 9, JCH = 127 Hz. The taller oftheimpuritypeaksnearii2.6correspondto (2R*,3R*)-3-butoxy2-methylpentanal and those near ii 2.8 to (2R*,3R*)-2-methyl3-(phenylmethoxy)pentanoic acid. (b) Lower curve: a 1:l mixture of 9 and ita (2R*,3S*)-epimer.
-
15
--
- -
a (a) LiCHClz (-100 "C); ZnClz (-100 +25 "C, 8-16 h);' (b) BnOLi, THF, -78 "C, DMSO (4 equiv), 25 "C 18 h; (c) CHaMgBr, -78 25 "C, 24 h; (d) H202,21 THFIHzO, pH 8-9; (e) HzOz, NaOH l l a , R1 = Bn, R2 = H; ClSiMezCMe3 l l b , R1 = Bn, R2 = SiMez(t-Bu); cyclohexene/Pd(OH)2, CaCOs, EtOH l l c , R1= H, R2 = SiMea(t-Bu); (0 (pyH)&r207, CHzClz, molecular sieves, 3 h; (9) BuzBOTf, i-PrzNEt, -78 "C, 0.5 h; 0 OC, 4 h;l6 (h) -78 0 "C, 15 h; (i) 25% CFsCOOH in CHC13,25 "C, 30 min.
-
suitable for the structure types.15 Aldol product 14 was oxidized with pyridinium dichromate to diketone 15, which readily ring closed with trifluoroacetic acid in chloroform to form O-benzylstegobiol(16), 43% based on 12 that had not been chromatographed. In most runs, 16 was chromatographed, but crystallizable stegobiol has been obtained without this step. Debenzylation of 16 to stegobiol(1) was readily accomplished with palladium hydroxide and cyclohexene in (15) (a) Paterson, I.; Lister, M. A.; McClure, C. K. Tetrahedron Lett. 1986,27,4787-4790. (b) Paterson, I.; McClure, C. K. Tetrahedron Lett. 1987,28, 1229-1232.
Figure 2. Magnified portion of the 300-MHz 1H-NMR spectrum of purified stegobiol(1). showing W-satellites, J = 144 Hz.(a) Upper curve: without detectable epi-stegobiol. (b) Lower curve: with -1% added epi-stegobiol, evident at 6 3.67, and accidental diethyl ether, 6 3.47 (9).
ethanol. The 0.5-1 ?4 of (l'R)-epimer was removed only by chromatography of stegobiol (1) [mp 73-74.2 'C (sealed tube, uncorrected); [CrIED -118.7' (17') (c = 0.107, CHCl3) (lit.2 [ ( U I ~-98.3' ~ D (c = 0.06,CHCl3); lit? [ C Y ] ~ D 110' (is")(c = 0.42, CHCb))], which failed to crystallize until this and other minor impurities were reduced to very low levels as shown by 'H-NMR analysis. Oxidation of pure 1withN-methylmorpholine N-oxidel tetrapropylammonium permthenate's yielded stegobinone
-
J. Org. Chem., Vol. 58, No. 24, 1993 6547
Communications
51.5-52.5 OC (uncorr) (1it.l mp 52.5-53.5 OC). Crystalline 2 stored 9 months at -15 "C did not contain sufficient
epimer 3 for detection (
