Alcohols 4a,b derived from ketone 3 were transformed, in the pentacyclic derivative 8. This procedure provides easy access to the 16-deethylapovincamine skeleton. acidic medium, to the rearranged compounds 6 (or 6Ј) and to
In a recent publication, dealing with the preparation of cohols 4a,b induced some unexpected rearrangements and cyclizations of the chloropropenyl side chain. Herein, we the indolcephalotaxane skeleton, we described the oxidative rearrangement of enamine 1 under BuzasЈ and HussonЈs wish to report a practical approach to the eburnane skeleton as shown in Scheme 2. conditions leading to the expected key intermediate pyrroloazepinoindole 2 accompanied by variable amounts of side Treatment of 4a,b with trifluoroacetic acid afforded the product ketone 3. This latter compound can be formed rearranged compound 6 (or 6Ј) [2] isolated in 53% yield, acfrom 1 by an dehydration followed by an allylic transpocompanied by 7% of ketone 3. The reaction was carried out sition of the chloropropenyl chain from position 1 to 12b.
in dichloromethane at room temperature. Since the transformation of 4a,b to 6 (or 6Ј) involves an oxidation and a transposition of the chloropropenyl chain, we can postulate that trifluoroacetic acid plays two different roles in the reaction as depicted in Scheme 3. The first step could be the formation of an indolo-iminium ion, obtained by proton transfer to C-12a from the protonated alcohols 4a,b, followed by transposition of the chloroallyl chain, leading to a highly oxidizable diamino derivative 7 which was not isolated. Since it has already been observed that amines are easily oxidized to imines or enamines by molecular oxygen in the presence of acetic acid, [3] we assumed that the intermediate 7 would evolve through oxidation to afford ketone 6. It should be pointed out that ketone 3 was unaffected by treatment with trifluoroacetic acid under the above conditions. This shows that 3 is not an intermediate in the transformation of 4a,b into 6 (or 6Ј).
Unfortunately, analogous behavior was not observed for alcohols 5a,b. They proved to be very sensitive to acidic conditions, especially to trifluoroacetic acid, whose action caused complete degradation.
When trifluoromethanesulfonic acid was used instead of Scheme 1. Assumed transformation of side product 3 into enamine 1 trifluoroacetic acid, 4a,b could be transformed into the pentacylic adduct 8 in 55% yield. This yield was increased With the aim of recycling, the tetracyclic ketone 3 was when the reaction was performed with concentrated sulfuric subjected to reduction affording, in the presence of Zn dust acid under the same conditions; in this case, 8 was isolated in acetic acid, the rearranged alcohols 4a,b, while sodium in 65% yield. In the 1 H NMR spectrum recorded in CDCl 3 , borohydride reduction led to the isomeric alcohols 5a,b. We the indole NH signal does not appear and the chemical shift hoped that derivatives 4a,b and 5a,b could be transformed value of the indolic C-6 proton (δ ϭ 8.12, d, J ϭ 8.5 Hz) into the desired enamine 1 by oxidation in acidic medium, suggests the formation of a new ring by a cyclization with followed by an allylic rearrangement in the case of 5a,b, as the allyl side chain to form a pentacyclic structure related depicted in Scheme 1. Surprisingly, acid treatment of alto apovincamine derivatives. The presence of a methyl group (δ ϭ 2.85) is in agreement with the structure of 8 [a] UPRES A CNRS 6013 "Isolement, Structure, Transformations which was confirmed by extensive COSY, HMBC and et Synthe `se de Produits Naturels" IFR 53 Biomole ´cules,