Nonphotochemical syntheses

Cyclization induced by chemical oxidants can successfijlly lead to the construction of aromatic rings even in elaborated polycycHc systems. However, the study of oxidative carbon—carbon bond formation as a way of constructing discrete thiophene-based materials has been relatively underexplored. 

The generation of carbon—carbon bonds by oxidative coupling between the two P positions of thiophene rings in dithienyl terminal-substituted alkenes requires the protection of the a and positions of the terminal thiophene rings. In fact, if these positions have no substituents, the thiophene 

An interesting chemical oxidative methodology, first reported many years ago (the Scholl reaction), has gained significant interest in recent years, due to its potential in the synthesis of several TT-conjugated materials. This reaction is an intramolecular oxidative C—C bond formation, mediated by various metal-based oxidants, between two benzenoid rings to produce a biaryl linkage and it has been extensively utilized for the synthesis of planar polycyclic aromatic compounds. 

As for the oxidative cyclization that uses iron(III) chloride, to effectively suppress the polymerization, the DDQ/acid-mediated variant of the SchoU reaction requires the blocking of the a positions of thiophene rings. 

In the synthesis of thiahelicenes, much attention has been focused on how to build, as the final synthetic step, a thiophene ring between two arene units. It is well known that there are a rather limited number of synthetic methodologies of general applicability to achieve this goal. 

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Syntheses of [n]helicenes (and [n]thiahelicenes) via oxidative photocyclizations of stilbenes have serious constraints. They must be carried out in dilute solutions ( 1 mM) and the functional groups that significantly affect relaxation of the singlet excited states of stilbenes such as bromo, iodo, keto, amino and nitro, are typically not compatible for longer helicenes, problems with regioselectivity of photocyclization may be encountered [61]. These limitations have spurred the recent developments of nonphotochemical syntheses for efficient preparation of highly functionalized, nonracemic helicenes. 

For nonphotochemical syntheses, there are three major approaches (1) annela-tion of racemic intermediate leading to racemic [njhelicene, followed by resolution, (2) annelation of nonracemic intermediate giving nonracemic [njhelicene and (3) asymmetric synthesis, i.e. annelation of racemic intermediate in the presence of chiral reagent, catalyst or auxiliary. 

To date, the reported nonphotochemical syntheses of racemic and enantiopure [w helicenes are limited to n = 9 and 8, respectively [62, 63], Recently, asymmetric syntheses of [njhelicenes with n up to 11 were developed in our laboratory [64]. 

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]. 

Elaboration of enantiopure (M)-[6]helicenebisquinone 12 into (M)-[8]helicene 13 with complete transfer of ee was reported (Fig. 15.5) [63]. [8]Helicene 13 is the longest enantiopure helicene prepared via nonphotochemical synthesis. 

Recently, Billups et al. reported an unusually short, nonphotochemical synthesis of grandisol based on the production of c/s-1,2-divinyl cyclobutanes from 1,3-dienes under influence of zero-valent nickel complexes. ... 

Hashimoto H, Matsuda A, Tobita H (2005) Nonphotochemical synthesis of a base-free silyl (silylene)iron complex and its reaction with CO another direct evidence for reversible 1,2-and 1,3-group migrations. Chem Lett 34 1374... 

A series of 3-alkyl- and 3-aryl-7/7-furo[3,2- ]-l-benzopyran-7-ones 78 (linear furocoumarins) was synthesized and evaluated for their photochemical and nonphotochemical crosslink formation with DNA as well as for their spectro-photometric and fluorescent properties, lipophilicity, and ability to photobleach A, A -dimethyl-/)-nitrosoaniline (RNO) after irradiation with UVA light <2002AP187>. The synthesis of the linear furocoumarins (Scheme 10) was a modification of a previously published method in which 7-hydroxy-2//-l-benzopyran-2-ones 76 were converted into / -ketoethers 77 by alkylation with haloketones under phase-transfer catalysis conditions. Base-catalyzed intramolecular condensation and subsequent acidification gave the corresponding 78. A molecular complex between each one of these fluorescent furocoumarins and DNA was observed, but only compounds with a 3-Me or 3-Ph group showed UVA irradiation-induced crosslink formation. 

To test this mechanism, a synthesis of species A by nonphotochemical means was undertaken. a -Haloketones, when treated with strong base, ionize to such dipolar intermediates ... 

Although the techniques of photochemistry may be inconvenient, especially for large-scale synthesis, the remarkable indole syntheses shown in this chapter—many of which have no nonphotochemical counterpart— shonld not be ignored by the organic chemist seeking to prepare a target indole or carbazole. 

The unsatisfactory results generally obtained in the stereoselective synthesis described in Section 3.2.1 and the limits of photochemical routes underline once more the need of developing nonphotochemical enantioselective procedures. Even if asymmetric synthesis is a key step in many synthetic procedures of organic chemistry, and has nowadays reached a high level of sophistication, only sporadic cases have been reported in the field of thiahelicenes. This might also be due to the complex synthetic methods known for the preparation of thiahelicenes. Hence, efficient enantioselective synthesis of heterohelicenes stiU represents a challenging goal. 

There is a significant potential to use photochemical energy to cause synthesis reactions to occur more efficiently and with less production of waste byproducts than nonphotochemical processes. One example is the acylation of benzoquinone with an aldehyde to produce an acylhydroquinone, an intermediate used to make some specialty polymers ... 

Helicenes and helicene-like molecules possessing nonplanar ortho-fused scaffolds exhibit helical chirality. Enantiopure forms of these molecules are potentially applicable to optical or electronic functional materials and chiral reagents [1], Therefore, development of their practical enantioselective synthesis, which can introduce various substituents on their frameworks, is highly attractive. The classical nonasymmetric synthesis of helicenes is based on an oxidative photocyclization of stilbene-type precursors [2]. However, this method suffers from low product yields and low substrate concentrations. Thus, several nonphotochemical synthetic methods have been developed which have been applied to the synthesis of enantioenriched helicenes [3]. Among them, a [2 - - 2 - - 2] cycloaddition strategy is highly attractive because of its convenient operation and its applicability to the catalytic enantioselective synthesis. The synthesis of helicenes and helicene-like molecules by transition-metal-mediated [2 -I- 2 -I- 2] cycloaddition reactions, including enantioselective variants, is summarized in this section. 

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