Racemic thiahelicene synthesis

The first [nfhelicenes, [6]pyrrolohelicene (2) and [5]helicene (3), were reported in 1927 and 1933, respectively [22-24]. The synthesis of a non-racemic [n]heli-cene, [6]helicene (1), was first described by Newman and Lednicer in 1956 [25], Photochemical syntheses developed during the 1960s and 1970s provided the longest [nfhelicenes to date, that is, [n]helicenes [with up to n = 14 benzene rings (4)] and [n]thiahelicenes [with up to n = 15 alternating benzene and thiophene rings (5)] [26-30]. 

Oxidative photocyclization of stilbene to phenanthrene, which was discovered in 1960, was first applied to the synthesis of [7]helicene by Martin and coworkers in 1967 [26, 44, 45]. This approach was extended to the syntheses of long [njhelicenes (n < 14) and [n]thiahelicenes (n < 15), using both mono- and diannelations. Numerous [nfhelicenes (n < 13) and [n]thiahelicenes (n < 13) were obtained in non-racemic form via the following methods (1) seeded crystallization of conglomerate (e.g. [7]-, [8]- and [9]helicene) [46, 47], (2) resolution by chromatography (e.g. [13]thiahelicene) [48] and (3) photocyclization from a resolved precursor (e.g. [13]helicene from hexahelicene-2-carboxylic acid) [49]. The oxidative photocyclization of stilbenes is still the method of choice for the preparation of selected [n]helicenes and their heteroatom analogs [50-58]. 

Annelation of racemic intermediate leading to racemic [n]helicene Larsen and Bechgaard reported the nonphotochemical synthesis of racemic [5]-and [9]thiahelicenes, relying on monoannelations of stilbene precursors [62], Electrochemical or chemical (FeCl3) oxidation was used in place of usual photooxidation, to provide thiahelicenes in 20-65% yields. For example, racemic [9]thiahe-licene 9 was obtained in —60% yield from stilbene 8 by oxidation with FeCl3 in methylene chloride (Fig. 15.3) a similar result was obtained by classical photooxidation of stilbene 8 [51]. 

Annelations via Diels-Alder reaction were employed by Katz and coworkers to develop exceedingly efficient methods for multi-gram scale syntheses of [n]heli-cenes with n up to 7. Efficient resolutions were carried out via functionalization with the camphanate ester derivatives and then separation of diastereomers by column chromatography (> 98% de). This synthetic approach may be illustrated by the synthesis of enantiopure [7]thiahelicene 10 [65]. Notably, the Diels-Alder diannelation and aromatization gives racemic 10 in 95 % yield. Resolution with camphanate tetraester provides enantiopure 11 (Fig. 15.4). 

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