Exocyclic reactions regioselectivity

The new family of phospholes with 2,4,6-trialkylphenyl substituent on the phosphorus atom show, in many respects, a special reactivity. Due to the flattening of the P-pyramid, the arylphospholes exhibit aromaticity and hence underwent Friedel-Crafts reactions. The regioselective functionalization through reaction with phosphorus tribromide gave a variety of phospholes with an exocyclic P-moiety. Novel phosphole platinum and rhodium complexes were prepared and a part of them was tested in hydroformylation reactions. 

Aryl or alkyl substituents on the exocyclic double bond steer the regioselec-tivity towards the formation of isoxazolidine-4-spirocyclopropanes 274-276 (Table 22, entries 1-3). A complete reversal of regioselectivity to 277-279 was observed in the reactions of methoxycarbonyl substituted methylenecyclo-... 

A positive feature of the reaction is that nitrile oxides are more regioselective, in cycloadditions to methylenecyclopropanes, compared to nitrones. Only traces (up to 5%) of the 4-spirocyclopropane regioisomers are generally observed with methylenecyclopropanes unsubstituted on the exocyclic double bond. The yields are only moderate, but higher with more stable nitrile oxides (Table 27, entries 5, 6, 10-12). 

The reactions of substituents on ring nitrogen atoms in 1,3,4-oxadiazolium cations 2 and exocyclically conjugated mesoionic 1,3,4-oxadiazoles 3 are uncommon. Similar reactions of compounds 4 and 5 were reported occasionally. Biphenylmethylation of 2-trifluoroacetamido-l,3-4-oxadiazole 105 occurred regioselectively (Scheme 23), affording only the 2-acylimino derivative instead of the expected product 106 <1997H(44)133>. 

Dipolar cycloadditions to electron-deficient allenes are not regioselective, taking place at the electron-poor C=C bond, in all cases. For example, the reaction of 372 with nitrile oxide 378 furnishes a mixture of products 379-383 [356], Obviously, 379, 380 and 381 result from different [2 + 3]-cycloadditions followed by tautomer-ism, whereas 382 and 383 are formed from the primary products of the 1,3-dipolar cydoaddition via addition of a second equivalent of 378 to the remaining exocyclic C—C bond. 

In addition to the high levels of asymmetric induction, two other attractive features of this sequence of reactions warrant comment. First, both acylation and hydrolysis of the chiral auxiliary are facile, high yield reactions. Second, we have recently found that the lithium hydroperoxide hydrolysis protocol described in Part C is the method of choice for the deaoylation process. This reagent exhibits remarkable regioselectivity for attack at the desired exocyclic acyl carbonyl moiety. ... 

In the first addition of nitrile ylides to a,()-unsaturated lactones (92), it was found that the reaction of benzonitrilio 4-nitrobenzylide with the lactones 178-180 were strongly regioselective. Compounds 178 and 179 reacted to give [e.g., 181 from 178 (51%)] and its methyl analogue from 179 (54%). The exocyclic double bond in 180 was, however, the most reactive and gave 182 (69%). The six-membered analogue of 178 was less reactive (34%) and the seven-membered analogue failed to react. 

Reaction of p-nitrobenzenesulfonyl azide with alkylidenecycloalkanes 22-25187 does not yield isolable triazolines as expected, but the reaction products derived from alkenes 22 and 23 suggest a single triazoline intermediate, whereas in the case of tetrasubstituted derivative 24 both possible reaction modes are present,187 owing to weak double bond dissymmetry. Product analysis from 25 indicates some conflict between electronic and steric control in the addition, but provides evidence that electronic factors are much more important than steric effects in controlling regioselectivity.187 Reaction of the exocyclic olefins 22 and 23 appears to be controlled more by the interaction of the LUMO of the azide and the HOMO of the alkene.187 p-Nitrobenzenesulfonyl azide is reported to react with members of the novel... 

The regioselectivity in lithiation of 1-methylpyrazole has been investigated by experimental, DFT and multinuclear NMR studies.61 In THF, 1-methylpyrazole reacts initially at the exocyclic a-position, to give an a-lithiated species which forms the thermodynamic product C(5)-Li in an intermolecular reaction. A coordination from N(2) to lithium apparently favours formation of the kinetic product a-Li. 

The use of quinone monoketals in the reaction with an exocyclic enaminoester is a new variation150. It is not a typical Nenitzescu reaction since an enamine anion is used. Tricyclic intermediates are obtained, which nevertheless formally give typical Nenitzescu products in high yield and regioselectively (equation 58). In this way annelated indoles of mitomycin type become accessible. 

The combination Sc02/tbhp has been successfully applied to a number of natural product syntheses a selection of some more recent examples is shown in Table 1. It is interesting to note that in six out of seven cases, exocyclic alkenes were used as substrates, and frequently very high yields were obtained. The stereoselectivity of hydroxylation is explained by a favorable ene reaction from the less hindered face of the double bond and the transition slate geometry of the subsequent [2,3] sigmatropic rearrangement. The regioselectivity, in particular entries 1 and 2, is less well understood. 

One application of the reaction shown in equation (52) is the conversion of cyclic, conjugated dienes into exocyclic alkenes. Although the stereochemistry of the reaction needs to be established, the cycliza-tion-protonolysis sequence may provide a convenient route to stereodefined exocyclic alkenes, as suggested by the examples given in equations (53) and (54). These reactions are all at least 90-95% regioselective, as judged by NMR. 

The radical cation Diels-Alder reaction has been the subject of many mechanistic and theoretical investigations and has been shown to have much synthetic potential. With regard to heteroaromatics, the reaction has been exploited by Steckhan in the cycloaddition of indoles and 1,3-dienes. This reaction occurs smoothly upon photosensitization by triarylpyrrilium tetrafluoroborates. The reaction is satisfactory rationalized as involving addition of the indole radical cation to electron-rich dienes (Scheme 35), and the regioselectivity is in accord with theoretical predictions [104]. The reaction with exocyclic dienes has been developed for the synthesis of carbazole derivatives such as 52 and 53 [105]. 

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