Regioselectivity cyclic ether reactions

Cyclic ethers were also obtained by cyclization of alkoxyl radicals, generated in a radical chain reaction by reacting the thione 42 with (TMSfsSiH under photochemical conditions at 20 °C (Reaction 46). Regioselectivities of cyclization have been investigated and a progressive increase of the 6-endo-trig selectivity along the series R2 = H[Pg.140]

According to the Baldwin rule, the exo cyclization mode is favored in intramolecular reactions of alkynyloxiranes with alcohols to afford cyclic ethers. However, the unfavorable endo cyclization mode is observed by the complexation. Thus exclusive endo cyclization of epoxide complex 146 takes place regioselectively to give 147, without forming the five-membered ether 148 by exo mode reaction [37]. 

The intermolecular coupling of allenes 123 and enones 124 selectively afforded dienones 125 in 53-81% yields (Scheme 4.45) [93]. As a catalyst precursor, [CpRuCl(cod)] was employed with CeCl3 7H20 and an alkynol 126 as activators. The proposed reaction mechanism involves the regioselective oxidative cyclization of the two components on a cationic ruthenium center, leading to the ruthenacyclopentane intermediate 127. When allenyl alcohols 128 were employed under otherwise identical conditions, the final products were cyclic ethers 129 (Scheme 4.46) [94]. As a catalyst precursor, the cationic ruthenium complex 68 can be used in the absence of the alkynol 126. The ether ring was considered to be formed directly via the ruthenacyclopentane 130 or alternatively through its Jt-allyl form 131. 

Diels-Alder cycloadditions have greater synthetic flexibility when suitable substituents on the diene are available for elaboration to functionality which is otherwise difficult to build into the structure. To this end, several schemes to novel 1,3-dienes have been described this year. Hagemann s ester (79) is a useful intermediate in synthesis of terpenoids. The ester is now conveniently available by regioselective Diels-Alder reaction of 1-methyl-l,3-bis(trimethylsiloxy)buta-1,3-diene (80) with ethyl acrylate. The yield is 61% overall after 5 days heating in xylene at 170—180 C, followed by hydrolysis of the moisture-sensitive adduct (81). The diene (80) is readily prepared from acetylacetone and trimethylsilyl chloride in the presence of triethylamine-zinc chloride in an ether-benzene mixture. The related diene (82), similarly prepared from 2-formylbutan-3-one, is used to give the useful cyclic dienophile (83). These sequences are outlined in Scheme 18. ... 

The first catalytic asymmetric selenoetherification of alkenes, studied by the same group, turned out to be a more diHicult process, due to the marked configurational instability of the enantioenriched seleniranium ions [101]. Nevertheless, the reaction afforded cyclic ethers in good yield, satisfactory regioselectivity, and moderate enantiocontrol when reacting alkenols with o-nitrophenyl-N-selenophthalimide, along with 10 mol% of catalyst 34 in the presence of methanesulfonic acid (Scheme 14.35). 

Hydroalkoxylation. The cycloisomerization of unactivated unsaturated alcohols has been achieved using Al(OTf)3 (eq Reaction with unsaturated oximes also led to 1,2-oxaza heterocycles with five-, six-, and seven-membered rings. This catalyst provided a straightforward route to cyclic ethers with a Markovnikov-type regioselectivity. Notably, these conditions were used for efficient synthesis of olfactory-active rose oxide derivatives. Mechanistic studies showed that Al(OTf)3 coordinates to the oxygen atom of the alcohol, leading to strong acidification of the hydroxyl proton. Intermolecular hydroalkoxylation with methanol has also been reported. ... 

Previous studies showed that the normal RCM reaction of simple triene (61) gave a poor regioselectivity to afford a mixture of five- and six-membered cyclic ethers. To resolve this problem, the authors tested a selective relay alkene RCM strategy, where the precursor (62) was modified to arm with an allyloxymethyl side chain. In this case, the initial ruthenium carbene species was selectively formed at the terminal alkene position of the allyloxymethyl side chain for both steric and electronic... 

Manganese A regioselective oxyalkylation reaction of vinylarenes (186) with cyclic ethers (187) can now be catalysed by the diatomite-supported Mn304 nanoparticles (SMONP-1). This new reaction gives rise to the addition products (188) resulting from the C-H activation next to the ether oxygen. 

Reductive C-N bond cleavage has been demonstrated in more complex systems using ethyl chloroformate as a solvent. Chlorination of corticosteroid cyclic ethers has been observed. Tertiary aliphatic and alicyclic amines can be dealkylated. Phenyl chloroformate, however, is usually regarded as the reagent of choice. In summary, deamination, demethylation, debenzylation, and deal-lylation of tertiary amines can all occur on treatment with ethyl chloroformate but the regioselectivities of these reactions are difficult to predict. ... 

Triplet photoaddition of simple non-cyclic monoolefins is unknown. The sensitized dimerization of ethyl vinyl ether gives exclusively head-to-head adducts, Eq. 21, and probably should not be classed as an example of simple acyclic olefin. Usually the triplets have high energies and are severly twisted. 55> Some cyclic rigid molecules, Eq. 20, that do dimerize 63> do not incorporate substituents that allow regioselectivity to be determined. Butadiene gives principally head-to-head dimerization, Eq. 19, concordant with the PMO prediction, and so does indene, Eq. 22. The anti dimer that is formed would not be expected from a singlet excimer reaction. 

The intermediate enolate or enol ether from the initial reduction of an enone may be alkylated in situ (Eq. 281).455 / -Substituted cyclopentenones may be asymmetrically reduced and alkylated459 (see section on asymmetric reductions of enones). Enolates may also be trapped with an aldehyde in a reductive aldol condensation of an enone with an aldehyde,455 permitting a regioselective aldol condensation to be carried out as shown in Eq. 282.455 This class of reductive aldol condensation reactions can also occur in a cyclic manner (Eq. 283).460... 

The reaction is applicable to acyclic and cyclic enol ethers and to various (3-dicarbonyl compounds, but fails with silyl enol ethers and simple 1,2-disubstituted alkenes. When applicable, this route to furans is useful because the yields and regioselectivity are consistently satisfactory. The paper includes a preparation of the reagent by reaction of Mn(NO,)3 with Ac20 at 100° to give Mn,0(0Ac)7 H0Ac in 60% yield. 

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