Regioselectivity lateral

This section details some recent examples of regioselective ring metalation and regioselective lateral metalation and subsequent functionalization. The examples were arbitrarily selected to demonstrate the versatility of such analogues. There is no attempt to include every metalated oxazole and the reader should consult the primary literature for additional examples. The synthesis and cross-coupling reactions of stannyloxazoles, silyloxazoles, and other organometallic oxazole analogues are discussed in Sections 1.4.8 and 1.4.9, respectively. 

In the case of the 2-dimethylamino- (or 2-amino-)methylene derivatives, the products were at first thought to be pyrimido[4,5-c]isoquinolines (267), but later work with 6-(N-substituted amino)uracils assigned the structures of the products (268) as belonging to the isomeric pyrimido[4,5-f>]quinoline system (74CB2537), in agreement with the regioselection rules above. 

The regioselectivity of the reaction with unsymmetrical alkynes is poor. Mixtures of isomers are obtained with alkyl substituted acetylenes, if the alkyl groups do not differ much in size. A solution to this problem has been reported by Semmelhack et al. The reactants are connected by a -OCHaCHaO-tether, which can later be removed the coupling step thus becomes intramolecular ... 

The analysis of the regioselective reactivity of olefins in identical topochemical environments by three computational methods concludes that both steric factors (cavity and potential energy) and electronic factors (perturbation energy from orbital interactions) play important cooperative roles in determining which C—C double bond in a molecule reacts first in [2-1-2] photodimerization. The steric factor is considered to be effective in the movement of olefins at an early stage of the reaction, whereas the electronic factors are effective in the adduction of olefins at a later stage of the reaction. 

This was later extended to the synthesis of novel pyrimido-[l,3-a]-pyrimidines under solvent-free conditions ethyl-2-armno-4-aryl-l,4-dihydro-6-phenylpyrimidine-5-car-boxylates react regioselectively with 3-formyl chromone or diethyl (ethoxymethylene) malonate, without solvent, to afford pyrimido-[l,3-a]-pyrimidines [92] (Scheme 8.66). 

Formation of a titanacyclopentane via cyclic dimerization of ethylene was reported as early as 197644 (Scheme 17). In marked contrast with the corresponding Zr-promoted reactions discussed later in this chapter, the intramolecular version of the Ti-promoted alkene-alkene coupling reactions does not appear to have been well developed. Consequently, detailed aspects of pair -selectivity and regioselectivity still remain largely unknown. 

The reaction sequence was later modified (74, 221) by carrying out the Dieck-mann ring closure on unsaturated ester 402. The process took place with total regioselectivity, thus resulting in 15,16-didehydroyohimbinone (410) as the sole product. Finally, catalytic reduction of 410 yielded ( )-yohimbine and ( )-0-yohimbine in a single step (74). 

The vinyloxirane reaction was later extended to methylidene cyclohexene oxide and to related meso derivatives [53]. The effects of the diastereomeric ligands 42 and 43 (Fig. 8.5), derived from (S)-binaphthol and (S, S)- or (R, R)-feis-phenylethyl-amine respectively, were investigated. In the case of kinetic resolution of racemic methylidene cyclohexane epoxide 45 with Et2Zn, ligand 42 produced better yields, regioselectivity, and enantioselectivity than 43 (Scheme 8.27). 

For cases where the regioselectivity of lithiation cannot be biased in the required direction, silylation can be used to block acidic sites while further lithiations are carried out. The blocking silyl group is later readily removed with fluoride . This method was used to avoid a competing lateral lithiation in the synthesis of the aldehyde 665 (Scheme 251... 

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