Tctrahcdron Letters, Vo131, No.36, pp 5221-5224.1990 Printed in Great Britain

oo4o-4039190 $3.00 + .oo Pergamon Rcss plc

A NEW SYNTHESIS OF 1 P-O-METHYL ROYLEANONEI

John King and Peter Quayle’ Department of Chemistry

The Victoria University of Manchester Manchester Ml3 9PL

and John F. Malone

School of Chemistry The Queen’s University of Belfast

Belfast BT9 5AG

The use of chromium carbene complexes for the synthesis of ditetpenoid q&ones is reported.

The synthesis of highly oxygenated dii and triterpenes continues to attract considerable attention’. Whilst a number of elegant approaches to a variety of these systems have appeared, the introduction of specific oxidation patterns remains a considerable synthetic challenge. In this communication we wish to report a novel synthesis of 12- O-methyl royleanone (1) as an illustratiie example of the use of vinyl chromium carbene complexes in the synthesis of terpenoid natural products2. Whilst-the Dotz beruannulation reaction3 has been extensively applied to the synthesis of natural products containing the naphthaquinone moiety (Scheme l), the use of simple vinyl chromium carbene complexes in an anatogous manner leading to benzoquinones has received much less attention4.

(i) X = Y 0

(ii) [Ol 0

Scheme 1

We envisaged that reaction of the vinyl carbene complex (2) with the oxygenated acetylene (3), would after oxidative work - up afford the desired quinone (1) (Scheme 2). Clearly, if this approach is to be synthetically useful, good regtocontrol in the initial benzannulatton is a prerequisite. The use of oxygenated acetylenes in the Dotx reaction has been reported in a limited number of cases5, hence it was anticipated that this study would serve as a useful model for determining the factors affecting the regiochemistry of these processes.

5221

5222

The desired vinyl chromium carbene complexes required in this study were conveniently prepared from the Wieland - Mieschler ketone (4). Selective mono-protection6 (MED; cat. TsOH; rt; 30 hrs). kinetic alkylation’ (KOtBu, 2.2 equ.; Mel, 9 equ.: 82%), deoxygenation at C3 ( N2H4 /A; 84%) and deprotection (aq. HOAc; 84%) afforded the 3, - unsaturated ketone

(S)*. Reaction of the ketone (5) with tri - isopropylphenylsulphonyl hydrazine in dry THF at room temperature for 24 hours cleanly afforded the hydrazone (6) in 87% yield as a single geometrical isomer (presumably the E- isomer on the basis of sterlc arguments) . Treatment of the hydrazone (6) with “BuLi (2.2 equ.) at -78OC in DME generated a red coloured di - anion which on warming up to -2OOC afforded a golden yellow solution of the vinyl carbanion (7)g. Upon re - cooling to -78OC the anion (7) was added to a slurry of chromium hexacatbonyl (1 equ.) in anhydrous DME. The reaction mixture was allowed to warm up to room temperature after which time complete dissolution was observed, producing a deep red - coloured solution of the acylate complex (8). The solvent was removed in vacua and the salt (8) redissolved in degassed water to whi% was added solid Et3OBF4 (1.5 equ.). The aqueous solution was

extracted with pentane; concentration of the organic extracts in vacua afforded the crude carbene complex ( 9) as a red - coloured oil. Attempted purfficatiin of the complex (9 ) proved problematical and was subsequently used without further purification. Reaction of the crude complex (9) with the acetylene (3)” (3 equ.) in refluxing, degassed THF was complete after 4 hours, and after an oxidative work - up (CAN, 7.5 equ. in 0.1 M HN03) afforded the

quinone (10)’ ’ p12 as an orange crystalline solid in 28% overall yield from the hydrazone (6). ’ H nmr (300 MHz) analysis of the crude reactbn mixture indicated that the reaction had proceeded in a totally regioselective manner. Proof of the regiochemical outcome of the reaction was unambiguously determined by a single crystal X - ray structure analysis# of (lO)(Figure 1).

Encouraged by these results, the decalone* (11) was converted, as above, to the isomerically pure hydrazone (12) in good yield (75%). Shapiro reaction9 of the hydrazone (12) and subsequent functbnalisation of the resultant vinyl carbanion (13) afforded the crude complex (2). Reaction of the crude product (2) with the acetylene ( 3) (3 equ.) in refluxing, de - gassed THF and oxidative work - up afforded 12 -O- methyl royleanone12 (1) in 37% overall yield from the hydrazone (12). Once again, unambiguous proof of the regiochemistry of the beruannutatbn reaction was secured by a single crystal X - ray diffraction study# of (1) (Figure 2). In conlusion. the Dotz benzannulation reaction has been shown to provide a highly convergent

and regioselective route to the synthesis of polyfunctionaliied diterpenes. Further applications of this basic strategy are currently under investigation.

OMe

0 \ & 0

\ )

(10)

5223

,NHSO.$r

2.2 cq. “BuLi c

-78°C to -20 ‘C

(11) (12)

(i) Cr (co)6 (i) )-0~e / A

Li

\

,p k (13)

- (2) * (1) (ii) Et30BF4

(ii) cAN/HNo,

Scheme

5224

Acknowledgements One of us (JDK) thanks the SERC for provision of an Earmarked Studentship. PQ thanks Pfizer Central Research for the provision of a travel award. q First presented at the RSC DaltonIPerkin International Symposium on “Synthetic

Applications Of Transition Metals”; St. Andrews, II-14 September 1989. References and notes (1) A. deGroot and T. A. van Beek, B8s.L Trav. Cbim., 1987,1p6,1 (2) For previous synthetic endeavours to this and related compounds see T. A. Engler, U.

Sampath, D. V. Vekfe, F. Takusagawa and D. Yohannes, J. 1989, x5712 and refs. therein

(3) K. H. Dotz, Aoaew.. Int. Fdn Fngt., 1984, a, 587. (4) S. Ft. Gilbertson and W. D. Wulff, synlett, 1989,47; for recent diversifications see T. A.

Brandvold, W. D. Wulff and A. L. Rheingold, & Am. Chem. Sgg., 199O,u,1645; V. Dragisch, C. K. Murray, B. P. Warner, W. D. Wulff and D. C. Wang, Q&t, 1990,112, 1251; W. E. Bauta, W. D. Wulff, S. F. Pakovic and E. J. Zaluzec, J., 1989,%, 3249

(5) A. Yamashita, T. A. Scahill and C. G. Chidester, -Letters, 1985,X, 1159; W. Flitsch, J. Lauterwein and W. Micke. Q&f, 1989, a, 1633

(6) G. Bauduin and Y. Pietrasanta, Tetrahedron, 1973, 8,4225. (7) c.f. J. S. Dutcher, J. G. Macmillan and C. H. Heathcock, ,I. Oro. Ch&t.~_ 1976,41,2663 and

refs. therein (8) J. T. A. Reuvers and A. deGroot, ,!. Ora. Chem, 1984,& 1110 (9) e.g. R. M. Adlington and A. G. M. Barrett, J.eSoc.,in Trans. 1,1981,2848; R.

M. Adlington and A. G. M. Barrett, Act. Chem., 1983,x, 55. (lO)J. R. Nooi and J. F. Arens, & Trav. (;him. 1959,B. 284. - (11)Representative spectroscopic data:- ir, ,,,‘1712, 1657 and 1608 cm-’ ; ‘H nmr (300

MHz; CDC5) 3 5.71 (1 H, dd, J = 5,2 Hz), 3.88 (3H, s), 3.20 (1 H, dd, J = 24,5 Hz),

3.16(1H,m),2.84(1H,dd, J=24,2Hz), 1.86(1H,ddt J =25,12,3 Hz), 1.50(3H, s), 1.21 (3H, d, J = 7 Hz), 1.18 (3H, d, J = 7 Hz), 1.13 (3H, s).

(12) After completion of our work the synthesis of the quinone (10) yia a Diels-Alder route was reported (ref. 2).

(13) Representative spectroscopic data:- ir, max 1708,1643, 1601 cm-’ ; 1 H nmr (300

MHZ; CDC13) 33.88 (3H, S), 3.17 (lH, S, J = 7 HZ), 1.30 (3H, S), 1.19 (6H, d, J = 7

Hz), 0.92 (3H, s), 0.89 (3H, s). Crvstal data for (1): Cpl H3003, M = 330.5, triclinic, a = 10.524(3), h = 12.514(3),

g = 7.978(3)A, II = 105.77(3), Q = 111 .01(2), a = 78.86(2)“, 1l= 938.5(5)A3, 2 = 2, D,

= 1 .I 7 g cm3, F(OO0) = 360, space group Pl (No. 2), MO-Ku radiation, h = 0.71073A, u(MO-Ku) = 0.42 cm-l. Clear, yellow blocks, dimensions 0.2 x 0.4 x 0.7 mm; Siemens P3/V2000 difractometer, 8-28 scans, 8 scan range 0.8O, 3 < 20 < 40”; 2444 unique reflections measured, direct methods solution (SHEIXSI) and least squares refinement (SHELX76); non-hydrogen atoms anisotropic, all hydrogens located in a difference Fourier synthesis but included at calculated positions with common isotropic temperature factors for methyl-methylene- and tertiary CH-type hydrogens which refined to final values of 0.127(4), 0.070(3) and 0.059(S) respectively. In the final cycles the 1748 data with F > 60(F) gave R = 0.049, Rw = 0.062 with weighting scheme 11y. = 0.861/[&F) + 0.00317F2]. Crvstal Data for (10): Cpl H2803, M = 328.5, Monoclinic, a = 12.750(4), b =

19.259(5), 0 = 8.001(3)A, Q = 107.79(3)“, U = 1870.6(1 o)A3, 2 = 4, D, = 1 .17 g cm4,

F(OO0) = 712, space group P2$ (No. 14), MO-Ku radiation, X = 0.71073A. u(MO-Ka =

0.43 cm-‘. Yellow-orange diamond plates, dimensions 0.1 x 0.4 x 0.8 mm; Siemens P3/V2000 diffractometer, e-28 scans, 8 scan range 0.8”, 3 5 20 zz 40”; 1739 unique reflections measured, direct methods solution (SHELXS86) and least squares refinement 9SHELX76); non-hydrogen atoms anisotropic, all hydrogens located in a difference Fourier synthesis but included at calculated positions. In the final cycles the 981 data with F 5 60(F) gave R = 0.049. R, = 0.054 with weighting scheme w = 1.084/[&F) + 0.00158F2].

Projections of the two molecules are shown in the Figures. Full crystallographic results have been deposited with the Director, Cambridge Crystallographic Data Centre, Lensfield Road, Cambridge CB2 1 EW, U.K.

(Received in UK 25 July 1990)