Reversibility regioselectivity

The most reactive site of the diene part is Cj of the cyclohexadienone ring with the alkoxy gronp. This corresponds to Cj of 2-alkoxybutadiene (Scheme 15), which has the largest HOMO amplitnde. The preferable frontier orbital interactions (Scheme 22) are in agreement with the reversed regioselectivities. 

On the other hand, condensation of 4,5-dihydrothiazole-2-amine (70a) with 65 follows reversed regioselectivity to give 1/7-isomer, i.e. 5,6-dihydrothiazolo[2,3-e]... 

Isoxazolines 38 and 39 were obtained in different ratios by direct cycloaddition of 4-t-butylbenzonitrile oxide with acids 35 (R = H, path B) and by the intermediate formation of cyclodextrin derivatives 36 and 37 followed by basic hydrolysis and acidification (path A). The reversed regioselectivity as well as an increased rate of the cycloaddition step could be explained through the temporary association of the nitrile oxide with the cyclodextrin to give the inclusion complex 40 <06CEJ8571>. 

Disubstituted 1,2,3-triazoles are formed in 1,3-dipolar cycloaddition of alkynylmagnesium reagents to azides. This reverse regioselectivity is also achieved in ruthenium-catalyzed cycloadditions. Examples of such reactions can be found in Section 5.01.9. 

An interesting antibody-catalyzed intermolecular asymmetric 1,3-dipolar cycloaddition reaction between 4-acetamidobenzonitrile N-oxide and N,N-dimethylacrylamide generating the corresponding 5-acylisoxazoline was observed (216). Reversed regioselectivity of nitrile oxide cycloaddition to a terminal alkene was reported in the reaction of 4-A rt-butylbenzonitrile oxide with 6A-acrylamido-6A-deoxy-p-cyclodextrin in aqueous solution, leading to the formation of the 4-substituted isoxazoline, in contrast to the predominance of the 5-substituted regioisomer from reactions of monosubstituted alkenes (217). 

Alk-2- and alk-3-ynoic acids are stannylated with Bu3Sn(Bu)CuCNLi2 to give the 3- and 4-stannyl derivatives, respectively, but the tributylstannyl ester of but-3-ynoic acid gives the reverse regioselectivity (Equations (30) and (31)).115... 

Attack of silver (I) ion, on the other hand, leads to a reversed regioselectivity, presumably through attack on the a-electrons of the cyclopropyl ring. This raises the question of whether such o-insertions are generally mediated by transition metals with cycloproparenes. 

Interestingly, in the reaction of 2-(3-chlorophenyl)-4,4-dimethyloxazoline with an alkyllithium [25], the deprotonation is chelation-controlled, but the addition of R" follows PAR. A reverse regioselectivity for alkylcuprate addition may well be explained by a complex-induced proximity effect which has been invoked to rationalize the alkyllithium additions. It is known that copper coordinates exceptionally well with amino and imino ligands. 

Diels-Alder reactionsThis reagent is more reactive in Dicls-Alder reactions than cyclohcxcnone. Treatment of the /i-nitro ketone with DBN effects elimination of HNO, to form the a,/ -enone.2 Thus the final products correspond to adducts of a "cyclohcxynone, but with reversed regioselectivity. 3-Nitro-2-cyclopentenone, m.p. 69- 7T, is also a useful dienophile (second example). 

The corrinoid-mediated reduction of polyhaloethenes has been the subject of a recent study, which reports reaction via homolytic C-halogen bond fission. The elimination of a further halogen radical affords haloalkynes, which lead to acetylene itself.56 The electron transfer-induced reductive cleavage of alkyl phenyl ethers with lithium naphthalenide has been re-examined in a study which showed that it is possible to reverse regioselectivity of the cleavage (i.e. ArOR to ArH or ArOH) by introduction of a positive charge adjacent to the alkyl ether bond.57 A radical intermediate has been detected by ESR spectroscopy in the reduction of imines to amines with formic acid58 which infers reacts takes place via Lukasiewicz s mechanism.59... 

Alkyl-substituted pyridinium salts also exchange benzylic hydrogens with deu-terated solvents with reversed regioselectivity in comparison with pyrylium salts because their y-anhydrobases are less stable than a-anhydrobases [57],... 

In the alkyne dimerization catalyzed by palladium systems, all proposed mechanisms account for an alkynyl/alkyne intermediate with cis addition of the alkynyl C-Pd bond to the alkyne in a Markovnikov fashion, in which the palladium is placed at the less-substituted carbon, both to minimize steric hindrance and to provide the most stable C-Pd bond (Scheme 2a). The reverse regioselectivity in the palladium-catalyzed dimerization of aryl acetylenes has been attributed to an agostic interaction between the transition metal and ortho protons of the aromatic ring in the substrate (Scheme 2b) [7, 8],... 

Reversed regioselectivity in aryl radical additions to enamides and enamines can also be observed with aryl substituents on the alkene [86]. This cyclization type has been successfully applied in the synthesis of protoberberines and the pavine alkaloids. Argemonine (39) was obtained from a 6-exo cyclization of 40 passing through a well-stabilized benzylic radical (Scheme 15). 

The AA with reversed regioselectivity (see above) of arylacrylates and heteroaromatic derivatives has been used in a number of applications. The AA of... 

Fig. 54.—Benzoylation of 2-phenyl-1,2-enthanediol with reversed regioselectivity.55-84...

Fig. 55—Tosylation of 3-0-benzyl-l,2-0-isopropylidene-< -D-glucofuranose with reversed regioselectivity.20...

The synthesis of furans from /3-ketoesters and a-halogenated aldehydes or ketones under basic conditions is known as the Feist-Benary furan synthesis (Equation 28). In most of the cases, the reaction is initiated by an aldol reaction. If the first step is alkylation, reversed regioselectivity is observed. 

This reaction was investigated particularly as a regioselective route to the pyridyl biaryl CD ring system of the antitumor antibiotic streptonigrin (5). Thus the reaction of the 1,2,4-triazine 2 with the morpholino enamine 3 gives the desired tetracyclic adduct 4 together with some of the adduct formed with reverse regioselectivity. This product was converted in several steps into a known precursor of the natural product. 

Compounds 3a and c give a reversed regioselectivity compared to the analogous reactions with alkylamine hydrofluorides (sec Section 1.1.4.3.2.1.5.) whereas compound 3b gives almost equal amounts of regioisomers with 70% hydrogen fluoridc/pyridine. The low yield in cases 3d and e may be due to the solvent used. 

---