Subject regioselective alkylation

One of the most defining characteristics of the late metal a-diimine polymerization systems is the uniquely branched polyolefins that they afford. This arises from facile p-hydride elimination that late transition metal alkyl complexes undergo. The characteristics of the isomerization process have been the subject of much investigation, particularly with the more easily studied Pd(II) a-diimine system. The process is initiated by P-hydride elimination from the unsaturated alkyl agostic complex 1.17, followed by hydride reinsertion into olefin hydride intermediate 1.18 in a non-regioselective manner (Scheme 5). In doing so, the metal center may migrate... 

The regio- and diastereoselective rhodium-catalyzed sequential process, involving allylic alkylation of a stabilized carbon or heteroatom nucleophile 51, followed by a PK reaction, utilizing a single catalyst was also described (Scheme 11.14). Alkylation of an allylic carbonate 53 was accomplished in a regioselective manner at 30 °C using a j-acidic rhodium(I) catalyst under 1 atm CO. The resulting product 54 was then subjected in situ to an elevated reaction temperature to facilitate the PK transformation. 

Meldrum s acid, like other 1,3-dicarboxyl compounds, was amenable to radical reactions at C-5. The radical reaction between Meldrum s acid benzyl alkyl ethers mediated by InCl3/Cu(OTf)2 has been reported to proceed regioselectively at the benzylic position of the ether moiety (Scheme 35) <2006AGE1949>. Radical reaction of Meldrum s acid and alkenes was carried out with 2equiv of ceric ammonium nitrate (CAN) to give the a-carboxy-lactones which were subsequently subjected to decarboxylative methylenation affording the a-methylene lactones in 35-50% yield (Scheme 35) <2006SL1523>. 

Theoretically, the regioselectivity observed in photochemical [2 + 2] cycloaddition of 56 with 1,1-dimethoxyethene is in good agreement with experimental results and has been explained on the basis of pertubational molecular orbital theory." Hartke and co-workers" described an interesting contrast in the reactivity of tropolones in an intramolecular Diels-Alder reaction (Scheme 6.18). Thus, alkylation of 64a and 64b with 65 gave 66a and 66b, respectively, that were subjected to cyclization in refluxing toluene. Whereas 66a decomposed under the reaction conditions, 66b afforded 67b in high yield. 

The addition of caibenoids derived from alkyl diazoacetates to alkenes has been extensively studied. As two thorough reviews on the subject,1 2 dealing with a detailed comparison of the various catalysts, have recently appeared, only a general summary concerning regioselectivity, competing reactions, dia-stereoselectivity and enantioselectivity will be presented here. 

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... 

Scheme IS depicts a high yield, general method for specific ortho alkylation of polycyclic aromatic hydrocarbons. In this example, biphenyl is subjected to reductive methylation followed by oxidative rearrangement with trityl tetrafluoroborate to give 2-methylbiphenyl. In unsymmetrical substrates the regioselectivity is poor phenanthrene gives a 3 2 mixture of 4-methyl- and 1-methyl-phenanthrene.

The Julia olefination reaction is highly regioselective and ( )-stereoselective, providing a valuable alternative to the Schlosser reaction for making rrans -disubstituted olefins. The reaction involves condensation of a metalated alkyl phenyl sulfone with an aldehyde to yield a P-hydroxysulfone, which is then subjected to a reductive elimination to produce the alkene. There are limitations to the preparation of tri- and tetra-substituted alkenes via the sulfone route because the P-alkoxy sulfones derived from addition of the sulfone anion to ketones may be difficult to trap and isolate or they may revert back to their ketone and sulfone precursors. 

Sodium borohydride and potassium borohydride react regioselectively with the formyl group of alkyl 2-formylcyclopropanecarboxylates lithium aluminum hydride is unseleetive. Stereospecific reduction of the formyl group was observed when formyl-cyclo-propanes were subjected to yeast alcohol dehydrogenase. ei Furthermore, regiospecific reduction of the aldehyde function in a 2-cyclopropylprop-2-enal derivative was performed using a mixture of sodium borohydride and cerium(III) chloride. 

An important family of disconnections follows. The alkylations represented by 4c(i), 4c(ii) and 4c(iii) belong to extended enolate chemistry and you will learn to call the synthons 9,10 and 11 the a, y and a extended enolates. Synthons 9 and 11 react in the normal d2 position but 10 has d4 reactivity. There are obvious questions of regioselectivity in this family. This chemistry will not be discussed further in this chapter as it is the subject of chapter 11. 

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