α-Oxoketene dithioacetals as intermediates for aromatic annelation

Abstract

The α-oxoketene dithioacetals of general formula 1 (Scheme 2), undergo regioselective 1,2-addition with allyl anions to afford the corresponding carbinol acetals 6 in quantitative yields, which on treatment with BF₃.Et₂O in refluxing benzene yield the corresponding aromatic systems. The method has been shown to be widely applicable as exemplified by a large number of allyl anions (Scheme 3) reacting with agr-oxoketene dithioacetals with wide structural variation. However, when 1 carry the agr-substituent the intermediate carbinol acetals 14 (Scheme 4) follow, different path to yield the corresponding indenes 15 in good yields. The cinnamoylketene dithioacetals 16 react with allyl anions to afford the corresponding methylthiostilbenes 18 (Scheme 5), while the homologous dithioacetal 20 failed to yield the corresponding 1,4-biaryl-1,3-diene 22 (Scheme 6). This limitation was circumvented by reacting 23 with allyl anions to afford the corresponding stilbenes 24, dienes 25 and triene 26 respectively. The method was successfully extended for naphthoannelation. Thus naphthalenes 28 (Scheme 7) were prepared by reacting benzylmagnesium chloride with 1. In this case the reaction followed a sequential 1,4-and 1,2-addition mode and yielded the corresponding benzyl substituted naphthalenes. This problem was solved by reacting benzylmagnesium chloride with 8 to afford the corresponding naphthalenes 31 (Scheme 8) in excellent yields. Similarly the lithio derivatives derived from toluene followed 1,2-addition mode with 1 to afford the derived methylthionaphthalenes 39 (Scheme 9) in high yields. The other alkyl substituted naphthalenes 41,43 (Scheme 9), 45,47 (Scheme 10) were similarly prepared. Also 1 and β-oxodithioacetals 8 reacted with 1-naphthylmethylmagnesium chloride to afford the corresponding phenanthrenes 49 and 51 respectively in good yields. The method was extended to benzanthracene 56 (Scheme 11) synthesis successfully. The 2-naphthylmethyl magnesium chloride reacted in a sequential 1,4- and 1,2- fashion to afford the corresponding naphthylmethyl hydrocarbons 58 while it reacted with β-oxodithioacetals to give expected condensed aromatics 60, 61 and 62 (Scheme 12) in high yields. The 1-naphthylmethylmagnesium chloride also reacted with β-oxodithioacetals 23 to afford the corresponding styrylphenanthrenes 65, dienes 66 and triene 67 respectively in high yields. The intermediate 69 precursor in the synthesis of hexahelicine was also obtained by reacting 68 with 1-naphthylmethylmagnesium chloride (Scheme 13). The oxygenated benzylmagnesium halides reacted with 1 in 1,2-fashion (Scheme 14) with the exception of the formation of 79. Five fold excess of Reformatsky reagent reacted with 1 to afford the corresponding salicylates 82 (Scheme 15) in high yields. Similarly 84 (Scheme 16) was formed. Propargylmagnesium chloride also reacted with 1 with the participation of solvent methanol to afford the corresponding thioresorcinol dimethylethers 86 (Scheme 17) in high yields. However, intermolecular solvent participation did not occur with open chain agr-oxoketene dithioacetals (Scheme 18) and the possible mechanism for this transformation is proposed (Scheme 19). The anion derived from aminocrotonate 97 (Scheme 20) reacted with 1 to afford the corresponding aminosubstituted aromatics 100. To prepare totally unsubstituted aromatics the allylanion was reacted with phenylthioacrolein 101 as exemplified by the synthesis of benzene 108a (Scheme 23), naphthalenes 109,110 and phenanthrene 111 (Scheme 24). In general our new method of aromatic annelation is a versatile, efficient and widely applicable for creating a large number of aromatics from easily accessible open chain precursors.