Non-beckmann rearrangement of a steroidal ketoxime

Non-beckmann rearrangement of a steroidal ketoxime

Telxah~lron Letters, Vol.32, No.38, pp5071-5072, 1991 Printed inGreat Britain 0040~t039/91 $3.00+ .00 Pergamon Press pie NON-BECKMANN REARRANGEMENT ...

90KB Sizes 0 Downloads 18 Views

Telxah~lron Letters, Vol.32, No.38, pp5071-5072, 1991 Printed inGreat Britain

0040~t039/91 $3.00+ .00 Pergamon Press pie


Giinter Neef* and GUnter Michl Research Laboratories of Scherlng AG Bedin/Bergkarnen, D-1000 Berlin 65, Germany Summary: On treatment with triflic anhydride/4-dimethylaminopyridine steroidal oxime 1_ reacts by hydride transfer to form a homoallylic carbocation which undergoes a cascade of subsequent transformations resulting in a new polycyclic system. Due to their structural rigidity the adducts II obtained by Diels-Alder cycloadditions to steroidal dienol acetates of type I represent unique tools to study neighbourlng group effects and interactions of reactive centers with a suitably located double bond.1





/ ~ X Ac



On treating oxime 12 with triflic anhydride (2 equiv.) in the presence of 4-dimethylaminopyridine (5 equiv.) in CH2C12 (60 rain, -70°- 0°C)3 we isolated the heterocyclic derivative 3 in a fairly good yield (77%) instead of observing the intended Beckmann fragmentation product 2. OAc

OAc 1

~ _


. "'"~N. OH




Obviously, neither normal Beckmann rearrangement nor fragmentation had occurred.4 A possible suggestion for product formation involves 1,4-hydride transfer to give homoallylic carbocation _5 which undergoes homoallyliccylopropyl carbinyl rearrangement to form cationic intermediate 6 which is perfectly prepared for ring closure as depicted in the scheme. Subsequent acylation of7_ by excess triflic anhydride forms the final product 3_. The highly selective formation of compound 3_ has to be regarded as a surprising outcome, since reactive species like iminium cations usually possess many alternatives, the most common of which is alkyl migration and subsequent interaction of the cationic intermediate with an internal double bond or an external nucleophile.5 5071






H "4-



_3 -,a._ NH

_7 TO t h e best o f o u r k n o w l e d g e , t h e r e is o n l y o n e case s i m i l a r to o u r s , r e p o r t e d in t h e literature. L a n s b u r y5 o b s e r v e d a f o r m a l i n s e r t i o n o f a n i m i n i u m c a t i o n i n t o a s u i t a b l y l o c a t e d C - H b o n d . L a n s b u r y ' s e x a m p l e a n d ours c l e a r l y d e m o n s t r a t e t h a t n o n - B e c k m a n n b e h a v i o u r is s u b j e c t to a s t r i c d y d e f i n e d s t e r i c p r e d i s p o s i t i o n b u t can b e m a d e a selective and preparatively u s e f u l process. References and Notes


(a) ].R. Bull and R.I. Themson, Y.Chem ~o¢.Perkin Trans. 1,241 (1990). (b) D. Sehemburg, M. Thielmarm and E. Winterfaldt, Tetrahedron Lett. 1986, 5833.


A.J. Solo, B.Singh, F. Shelter and A. Cooper, Steroids 11,637 (1968).3


Slight variation of a procedure developed by E. Ottow, unpublished results


R.T. Conley and S. Gliosh in Mechanisms of Molecular Migrations, B.S. Thyagarayan, ed., Wiley lnterscience, N. Y. 1971, vol. 4, pp 197-308.


(a) P.T. Lansbury, Nilxenium Cations in Nitrenes, W. Lwowski, ed., Intersciences Publishers New York 1970, pp 405-419. (b) K. Maruoka and H. Yamamoto, Angew.Chem. 97, 670 (1985). (c) R.E. Gawley and E.J. Termine, J.Org.Chem. 49, 1946 (1984).


(a) P.T. Lansbury and N.R. Mancuso, ibid. 88, 1205 (1966). (b) R. Griot and T. Wagner-Jaurreg, Helv.Chim.Acta 42, 605 (1959).


Compound 3_: rap. 12.3-125°C; [a]D25 + 56,8" (CHCI3, c--0,515);

1H-nmr: ~=1,03 ppm (s, 3H, H-18); 1,00-_1,17 (m, 1H, H-Tax); 1,37-1,50 (2H, H-7eq, H-11ax); 1,56-1,64 (m, 1H, H-12ax); 1,65-131 (m, 1H, H-12eq); 1,74-1,83 (m, 2H, H-19, H-15); 1,86-1,95 (m, 1H, H-8); 2,06 (s, 3H, H-25); 2,32-2,48 (m, 2H, H-9, H-1 leq.) 2 75-2 90 (m, 2H, H-6ax, H-6eq); 3,49 (s, 1H, H-20); 3,77 (s, 3H, H-26); 4,60 (d, J=2Hz, 1H, H-22); 5,03 (s, 1H, H-16); 5,04 (d, J=2Hz, 1H, H-22); 6,61 (d, J=3Hz, 1H, H-4) 6,72 (dd, J=8 or 3Hz, 1H, H-2); 7,21 (d, J=SHz, 1H, H-l). 13C-nmr: 8=15,7 ppm (q, C-18); 20,3 (d, C-15 or C-19); 20,9 (d, C-19 or C-15); 21,1 (q, C-25); 23,4 (t, C-7); 26,5 (t, C-11); 29,6 (r, C-6); 32,4 (t, C-12); 34,4 (d, C-8); 38,3 (s, C-13 or C-14); 42,8 (d, C-9); 44,3 (s, C-14 or C-13); 53,3 (d, C-20); 55,2 (q, C-26); 68,1 (d, C-16); 90,6 (s, C-17), 93,0 (t, C-22); 111,9 (d, C-2); 113,8 (d, C-4), 119,9 (q, C-23); 126,7 (d, C-l); 131,4 (s, C-10); 137,4 (s, C-5); 143,4 (s, C-21); 157,7 (s, C-3), 169,6 (s, C-24) MS-EI (r¢l. int.): 523 (43); 390 (8); 362 (10); 268 (18); 227 (64); 215 (17); 173 (9); 147 (13); 57 (62); 43 (100) The nmr spectra were recorded on a Bruker AMX-500 using standard software. Proton spectra were run in CDCI3 , tetramethylsilane serving as internal standard. 13C chemical shifts were determined relative to solvent signal ~(CDC13)= 77 ppm. o 12



( R e c e i v e d in G e r m a n y 2 7 J u n e 1 9 9 1 )


11~7 ~



0 ~25


N/SO2 21