Naphthyl-substituted substrates

Even better regio- and enantioselectivities were observed when 1-naphthyl-substituted allylic acetates (10b and 11b) were used. The regio- and enantioselectivities were essentially the same using either the achiral substrates (10) or the racemic isomers (11) (eq 3, Table 1). 

In comparison, 1-naphthyl-substituted derivatives were more potent inhibitors (IC5Q= 10 nM) with similar activity to epalrestat. 4-Oxo-2-thioxo-5-(2-naphthylmethylene)-3-thiazolidine-acetic acids were obtained by the condensation of substrate 4 with appropriate 2-naphthaldehydes. Results of in vitro studies related to these two classes of compounds are represented in Table 9.3 [16]. 

In conclusion, the use of naphthylpropionic acids as CDAs is limited by (a) the small number of substrates of known absolute configuration used to validate the method and (b) the absence of information about their conformational characteristics. The shifts obtained are smaller than those observed for other, better-known naphthyl-substituted reagents and, therefore, do not provide any advantage. 

In addition to naphthyl substituted alkynes, 2-methoxy-tetrahydronaphthalen-1-yl- and 2-methoxy-6-methylphenyl alkynes were shown to be suitable substrates affording the corresponding pyridones with e.e.s >90%. 

Meyers has demonstrated that chiral oxazolines derived from valine or rert-leucine are also effective auxiliaries for asymmetric additions to naphthalene. These chiral oxazolines (39 and 40) are more readily available than the methoxymethyl substituted compounds (3) described above but provide comparable yields and stereoselectivities in the tandem alkylation reactions. For example, addition of -butyllithium to naphthyl oxazoline 39 followed by treatment of the resulting anion with iodomethane afforded 41 in 99% yield as a 99 1 mixture of diastereomers. The identical transformation of valine derived substrate 40 led to a 97% yield of 42 with 94% de. As described above, sequential treatment of the oxazoline products 41 and 42 with MeOTf, NaBKi and aqueous oxalic acid afforded aldehydes 43 in > 98% ee and 90% ee, respectively. These experiments demonstrate that a chelating (methoxymethyl) group is not necessary for reactions to proceed with high asymmetric induction. 

Indoles, pyrroles, and carbazoles themselves are suitable substrates for palladium-catalyzed coupling with aryl halides. Initially, these reactions occurred readily with electron-poor aryl halides in the presence of palladium and DPPF, but reactions of unactivated aryl bromides were long, even at 120 °C. Complexes of sterically hindered alkylmonophosphines have been shown to be more active catalysts (Equation (25)). 8 102 103 In the presence of these more active catalysts, reactions of electron-poor or electron-rich aryl bromides and electron-poor or electron-neutral aryl chlorides occurred at 60-120 °C. Reactions catalyzed by complexes of most of the /-butylphosphines generated a mixture of 1- and 3-substituted indoles. In addition, 2- and 7-substituted indoles reacted with unhindered aryl halides at both the N1 and C3 positions. The 2-naphthyl di-t-butylphosphinobenzene ligand in Equation (25), however, generated a catalyst that formed predominantly the product from A-arylation in these cases. 

The reaction of aryl and hetaryl halides with the nitrile-stabilized carbanions (RC -CN) leads to derivatives of the type ArCH(R)CN. Sometimes, however, dimeric products of the type ArCH(R)CH(R)Ar are formed (Moon et al. 1983). As observed, 1-naphthyl, 2-pyridyl, and 2-quinolyl halides give the nitrile-substituted products, while phenyl halides, as a rule, form dimers. The reason consists of the manner of a surplus electron localization in the anion radical that arises upon replacing halogen with the nitrile-containing carban-ion. If the resultant anion radical contains an unpaired electron within LUMO covering mainly the aromatic ring, such an anion radical is stable, with no inclination to split up. It is oxidized by the initial substrate and gives the final product in the neutral form, Scheme 1-7 ... 

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