Ter r ahedr on Vol. 46, No. 12, pp 44434456, 1990 oo4wo20/90 s3.00+ .I0 Prmted m Great Brian 0 1990 Pergamon Pnss plc STUDIES ON THE SYNTHESIS OF INDOLO[2,3-a]QUINOLIZIDIN-2-ONES. II1 Mario Rubiralta,* Anna Diez, and Cristina Vila Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona. 0802SBarcelona. Spain zyxwvutsrqponmlkjihgfedcbaZYXW (Received in UK 30 March 1990) Abstract- The synthesis of indolo[2,3-alquinolizidin-2-one (la) has been accomplished by the d&ct cyclization of N-hydroxyethyl-2-[1-@henylsulfonyl)-2-indolyl]4pi~done ethylene acetal(4) with KtBuO. Nevertheless, treatment of the 3-ethylpiperidine analogue 16 with KtBuO only led to the corresponding hexahydm-4Wpyrido [ 1’,2’: lZ]pyrazino [4,3-&dole (23). resulting from the cyclization upon the indole nitrogen. The indolo[2,3-alquinolizidin-2-one framework la2-9 is integrated in the structure of several key intermediates in the synthesis of pentacyclic indolo[2,3-alquinolizidine alkaloids. The great majority of such compounds are substituted on position 38910-14 and only two cases of C-l substituted derivatives have been reported (see Figure 1).15916 Indolo[2,3-ulquinolizidin-2-one itself (la) has been extensively studied and its synthesis has been carried out by two general synthetic strategies consisting in the elaboration of rings C or D in the key steps. Thus, elaboration of ring C has been carried out by formation of the C12a-C12b bond,4 while ring D has been constructed by i) a Dieckmann cyclization of the appropriate diester,3,6 ii) an hetero Diels-Alder or a Michael-Mannich tandem reaction applied on dihydrocarbolines,738 iii) by formation of N-C4 bond,2 and iv) by application of the acid catalysed rearrangement of isoxazoline-Sspiro cyclopropanes.9 These numerous synthetic studies arise from the application of la in the synthesis of related compounds to Rauwolfia and Yohimbe alkaloids such as reserpine 17 and yohimbine6. Moreover, other important synthetic intermediates are 3- and 1-ethylindolo[2,3-ulquinolizidin-2-ones zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPO lb and 2, respectively. In spite of the fact that 3-ethylderivative lb has been synthesized lo-12 and applied to the synthesis of dihydrocorynantheine,lg corynantheidinelg*l!J and flavopereirine 20 alkaloids , no synthesis has been described for its l-ethyl analogue 2. However, the 1-ethyl-1-methoxycarbonylmethyl derivative lk has been prepared and applied to the synthesis of ebumamonine.15 8 7 la R1=R2=R3=H (Ref. 2-9) b f+Rz=H; R3=C2H5 (Ref. 10-12) c R1-R~H; R3=CH3 (Ref. 10-12) d Rl=Rz=H; Rs=n-CsHT (Ref. 10,12) 4 e R,=RpH; R+C&3(Ref. 10.12) 3 f RI=R2=H; R3=CH2Ph (ref. 10, 12) ‘Q, g Rf=RpH; Ra=COCHa (Ref. 13) A3 h F+R2=H; R3=COOC2H5 (Ref. 3,13) I R,=Rz=H; R3=CH@QCH3 (Ref. 8,12) 0 j Rl=Rz=H; CH2CH2COOCH3 (Ref. 12,14 k R1+l+,; R2=CH2COOCH3; R3=H (Ref. 15) I Rf=CH$H$XOCH3; Rz=Ra=H (Ref.16) Figure 1 4443