Rearrangement regioselectivity

Kunishima, M. Hioki, K Kono, K Kato, A. Tani, S. Sml2-Induced 2,3-Wittig rearrangement regioselective generation of a-allyloxy carbanions via 1,5-hydrogen transfer of vinyl radicals./. Org. Chem. 1997, 62, 7542-7543. 

Rearrangements. Regioselective ring contractions are possible via hromination of cyclobutyl ketones. The intermediate bromo ketone, when treated with silver acetate in acetic acid (120 °C, 6 h), affords a mixture of the cyclopropyl ketone and the acetoxy ketone (57% and 28% isolated yield, respectively, eq2).2... 

Dehydration of alcohols (Sections 5 9-5 13) Dehydra tion requires an acid catalyst the order of reactivity of alcohols IS tertiary > secondary > primary Elimi nation is regioselective and proceeds in the direction that produces the most highly substituted double bond When stereoisomeric alkenes are possible the more stable one is formed in greater amounts An El (elimination unimolecular) mechanism via a carbo cation intermediate is followed with secondary and tertiary alcohols Primary alcohols react by an E2 (elimination bimolecular) mechanism Sometimes elimination is accompanied by rearrangement... 

Dehydrohalogenation of alkyl halides (Sections 5 14-5 16) Strong bases cause a proton and a halide to be lost from adjacent carbons of an alkyl halide to yield an alkene Regioselectivity is in accord with the Zaitsev rule The order of halide reactivity is I > Br > Cl > F A concerted E2 reaction pathway is followed carbocations are not involved and rearrangements do not occur An anti coplanar arrangement of the proton being removed and the halide being lost characterizes the transition state... 

Hydroboration-oxidation of alkenes (Section 6 11) H and OF add to the double bond with a regioselectivity opposite to that of Markovnikov s rule This is a very good synthetic method addition is syn and no rearrangements are observed... 

Substituted TMM complexes also cycloadd to aldehydes in the presence of a tin cocatalyst such as MesSnOAc and MesSnOTs [31]. Reaction of 2-heptenal with methyl precursor (6) gave a mixture of methylenetetrahydrofurans (68) and (69). This regioselectivity is reversed with 10-undecenal and methyl precursor (5), where adduct (70) now predominates over (71). As in the carbocyclic system, the phenylthio group also functions as a regiocontrol element in reaction with cyclohexyl aldehyde. The initially formed adduct (72) eliminates the element of thio-phenol on attempted allyl rearrangement, and the overall process becomes a cycloaddition approach to furans (Scheme 2.21) [20]. 

Since the Fries rearrangement is a equilibrium reaction, the reverse reaction may be used preparatively under appropriate experimental conditions. An instructive example, which shows how the regioselectivity depends on the reaction temperature, is the rearrangement of m-cresyl acetate 8. At high temperatures the ortho-product 9 is formed, while below 100°C the para-derivative 10 is formed ... 

Interestingly, treatment of bicyclic imidate 5 (R = OMe) with lithium diisopropylamide at — 78 C, followed by addition of iodomethane and quenching into ammonium chloride solution, gives 2-methoxy-3-methyl-37/-azepine. In the absence of iodomethane, 2-methoxy-3i/-azepine (6, R = OMe) is produced. Rearrangement of the lithiated bicycle to a lithiated 2-methoxy-3//-azepine, followed by regioselective trapping by the electrophile, is the most likely mechanistic rationale. 

Ethyl 1 /T-azepine-l-carboxylate (1) and l,3-diphenyl-2/7-cyclopenta[/]phenanthren-2-one (26) (phencyclone) in refluxing benzene undergo a rapid peri- and regioselective cycloaddition to give the [4 + 2] 7t-e rfn-adduct 28 and not, as was first proposed, a [6 + 2] 7r-adduct.264 Subsequently, however, it was found that at room temperature a [2 + 4] 7r-cw/<>-adduct 27 is formed which readily undergoes a Cope rearrangement to the [4 + 2] endo,anti-adduct 28. 

A major disadvantage of this procedure is the lack of regioselectivity of the bishydroxylation which can take place on each of the four pyrrole rings of the macrotetracycle so that, in addition to the monoadduct, two bisadducts and one trisadduct are formed. The subsequent pinacol rearrangement of the diols can also occur in two directions, leading to a complex mixture of additional constitutional isomers. 

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