Thallium Trinitrate Mediated Ring Contraction of cis-2-Decalones

improved under this condition, the reaction occurred with low regioand diastereoselectivity, being observed three diastereomers of the four possibles (Table 1, entry 1). Two aspects can be invoked to explain this low selectivity. First, the formation of both enol forms of the ketone 112, which is responsible for the low regioselectivity. The ∆1,2 enol leads to the hydrindanes substituted at C1 position, whereas the ∆2,3 furnishes the carboxyl group at the C2 position (Figure 1). In 1988, Huffman and Balke 13 showed that the decalone 1 gives a slightly excess of the ∆2,3 trimethylsilyl enol ether, under thermodynamic conditions (TMSI/(Me 2Si)2NH/ CH2Cl2), which agrees with our result. The second aspect concerns the flexibility of the cis-fused system, which allows the trans-diaxial addition from both faces, thus explaining the low diastereoselectivity (Figure 1). We have no explanation for the fact that only three of the four possible diastereomers have been formed in the ring contraction reaction. *e-mail: hmferraz@iq.usp.br H O O

Cis-fused hydrindanes are an important moiety present in several natural products, such as bakkenolide-A 1 and thapsanol 2 .In the course of the synthesis of these challenging targets, we sought for an efficient method to promote the ring contraction of cis-2-decalones.improved under this condition, the reaction occurred with low regio-and diastereoselectivity, being observed three diastereomers of the four possibles (Table 1, entry 1).Two aspects can be invoked to explain this low selectivity.First, the formation of both enol forms of the ketone 1 12 , which is responsible for the low regioselectivity.The ∆ 1,2 enol leads to the hydrindanes substituted at C1 position, whereas the ∆ 2,3 furnishes the carboxyl group at the C2 position (Figure 1).
In 1988, Huffman and Balke 13 showed that the decalone 1 gives a slightly excess of the ∆ 2,3 trimethylsilyl enol ether, under thermodynamic conditions (TMSI/(Me 2 Si) 2 NH/ CH 2 Cl 2 ), which agrees with our result.The second aspect concerns the flexibility of the cis-fused system, which allows the trans-diaxial addition from both faces, thus explaining the low diastereoselectivity (Figure 1).We have no explanation for the fact that only three of the four possible diastereomers have been formed in the ring contraction reaction.Thallium(III) salts have been successfully used in the ring contraction of trans-2-decalones 3 , as well as steroidal ketones 4,5 , although some exceptions have also been reported 4,6 .However, only two papers describing the reactions of cis-2-decalones or related compounds with thallium(III) salts have been published 7,8 .In both of them, a single ring contraction product was obtained in low yield, as exemplified in Scheme 1.We anticipated that the low yield could be overcome using different experimental conditions for promoting this ring contraction 3,[9][10][11] and, consequently, an efficient methodology for constructing cishydrindanes could be established.
The first substrate studied was the decalone 1 (see Table 1), which was treated with thallium trinitrate (TTN) in CH 2 Cl 2 at room temperature.Although the yield was indeed Under similar reaction conditions, the 9,10-dialkyldecalones 2 and 3 led to the diastereomeric ring contraction products 8a/8b and 9a/9b, respectively (Entries 2 and 3).These results suggest that only the ∆ 2,3 enol was formed from the substrates 2 and 3. Therefore, the presence of two alkyl groups at the ring junction increased the regioselectivity, when compared to the substrate bearing an hydrogen at the same position.
The introduction of a methyl group at C8 position shows pronounced effect not only in the regio-, but also in the diastereoselectivity, as observed in the reaction of the decalone 4 with TTN.This reaction led to the formation of a single diastereoisomer of each regioisomeric acids 10 and 11, in a 10:1 ratio (Entry 4).
On the other hand, in the ring contraction of the decalone 5, which bears a methyl group at C5, an inversion in the regiochemistry of the reaction was observed, when compared to the other cis-fused substrates studied.In this case, the ∆ 1,2 enol form was the preferable pathway of the reaction (Entry 5).The ring contraction of the cis-decalone 5 promoted by SeO 2 was investigated by Da Silva 14 , in 1984.Using this oxidant, the acids 12 and 13 were obtained in a 2:3 ratio, respectively.It is worth noting that the result of the ring contraction of the decalone 5 was critical in our initial plan to the synthesis of bakkenolide-A.Due to the observed regioselectivity, a new route is being planned to achieve the desired carboxylic acid 12.
It is interesting to note that the 2-substituted hydrindanes 6, 10 and 12 can be distinguished from the corresponding 1-substituted 7, 11 and 13, respectively, by 13 C NMR. a The ratio was determined by 13 C-NMR (Inverse Gated Decoupling), except for 12:13, which was estimated by GC and 1 H-NMR analysis; b Single stereoisomer.Relative configuration not determined; c Relative configuration determined by comparison with literature 14 .The carbon attached to the carboxyl group in 6, 10 and 12 is shielded by ca. 5 δ when compared to the 1-substituted hydrindanes.Thus, it was possible to determine their ratio by inverse gated decoupling.

H
In contrast to the behavior of the cis-decalones 1, 4 and 5, the reaction of the corresponding trans-2-decalones, under similar conditions, has furnished a single ring contraction product, as exemplified for trans-10-methyl-2-decalone in Scheme 2 3,15 .
In summary, we showed that cis-2-decalones furnish ring contraction products in good yields, although in low regio-and diastereoselectivities (except for the substrate 4).We also revealed that the effect of the alkyl groups in the ring contraction depends on their position in the decalone ring system, in a non-straightforward manner.Changing the alkyl group from methyl to n-butyl in the ring junction slightly increased the diastereoselectivity of the reaction.

Experimental
Caution! Thallium(III) salts are toxic and must be handled with care.

Table 1 .
Reaction of cis-2-decalones with TTN in CH 2 Cl 2 at room temperature.