Selected substituent effects on the rate and efficiency of formation of an eight-membered ring by RCM

Studies of a range of reactions forming cyclooctenones highlight a discrepancy between cyclization rate and cyclization efficiency. Cyclization rates change modestly as the oxygen function at the allylic position is varied, and increase upon gem-dimethylation. Cyclization efficiency has also been quantified for four substrates, revealing a range of effective molarities (EMs) of 2 orders of magnitude that are substituent dependent. The most efficient cyclization appears to result from suppression of the cross-metathesis pathway through which oligomerization begins, rather than from a particularly rapid cyclization reaction. In the presence of a Ti(IV) cocatalyst, diene monomers transform smoothly to eight-membered-ring products without the intermediacy of dimers or other oligomers, indicating that the cyclizations are kinetically and not thermodynamically controlled. The gem-dialkyl effect is also shown to be kinetic.     

A silicon-position dependent 6-endo-trig cyclization during Tsuji–Trost alkylation

Two silylated cyclohexenes products have been prepared by using a Tsuji–Trost palladium-catalyzed cyclization. It involves the generation of a cationic π-allylic palladium complex bearing a triethylsilyl group on C-3, which cyclizes via a 6-endo-trig process to afford the cyclohexene derivatives. It is also demonstrated that the position of the silyl group on the starting allylic substrate strongly influenced the reaction. It could favor either the production of the expected cyclohexenyl ring or a diene by an elimination that occurs on the silyl-substituted C-2 π-allylic palladium complex.     

Palladium-catalyzed cyclization reaction of allylic bromides with 1,2-dienyl ketones. An efficient synthesis of 3-allylic polysubstituted furans

3-Allylic polysubstituted furans were synthesized via a palladium-catalyzed cyclization reaction of allylic bromides with differently substituted 1,2-allenyl ketones. This process may occur via the reaction of a furanyl palladium intermediate with allylic bromide.     

Reversal of facial selectivity in complex Diels-Alder reactions

A complex Diels-Alder reaction between a semi-cyclic diene with allylic silyloxy substituents and a bromo enone presented an unusual diastereoselectivity: attack of the diene occured on its more hindered face, and this reversal of selectivity was shown to be induced by the presence of a bromo substituent in the dienophile.     

Novel Synthesis of Dihydrothiazoles from the Selenium‐Induced Cyclization of Allyl Thioureas

The reaction of allylic thioureas with phenylselenenyl chloride affords 2‐amino dihydrothiazoles in excellent yields by selenium‐induced cyclization of allylic thioureas.     

Palladium-catalyzed regio- and enantioselective allylic alkylation of bis allylic carbonates derived from Morita-Baylis-Hillman adducts

Morita-Baylis-Hillman diene adducts are used as substrates in the palladium-catalyzed asymmetric allylic alkylation reaction with oxygen and carbon nucleophiles in good regio- and enantioselectivity.     

Atom transfer cyclization catalyzed by InCl3 via halogen activation

[reaction: see text] Indium trichloride was found to be an efficient catalyst for the cyclization of allylic halides and alkynes with atom transfer in methylene chloride. Mechanistic evidence supports a cationic reaction pathway with Lewis acid activation of the allylic halogen. Concomitant nucleophilic attack by the alkyne and trapping with halide led to atom transfer cyclization products. Depending on alkyne substitution, a bromine atom was transferred from the substrate or a chlorine atom was transferred from the solvent.     

Synthesis of ent-haterumalide NA (ent-oocydin A) methyl ester

[reaction: see text] Stille coupling of allylic chloride 26 with vinylstannane 4a afforded 65% of 27 with the requisite skipped diene, vinyl chloride, and allylic oxygen functionality. Yamaguchi macrolactonization of 28 provided 65% of 29, which was elaborated to haterumalide NA methyl ester (32) by a Nozaki-Hiyama-Kishi coupling with 31.     

A new paradigm for cationic cyclization of iron tricarbonyl diene complexes with pendant alkenes and arenes

A new example of stereospecific cationic cyclization of iron tricarbonyl diene complexes with pendant alkenes and arenes is provided. Protonation of a double bond vicinal to the iron tricarbonyl diene moiety is employed to trigger the cyclization, rather than the previously reported Lewis/protic acid dehydroxylation of diastereomeric alcohols, eliminating one step of separation and avoiding some reactivity problems previously encountered for one of the alcohol diastereoisomers. [reaction: see text]     

α,β-Divinyl tetrahydropyrroles as chiral chain diene ligands in rhodium(I)-catalyzed enantioselective conjugated additions

A series of α,β-divinyl tetrahydropyrroles, synthesized by asymmetric allylic C-H bond activation/conjugated diene addition reaction of ene-2-dienes, were found to be very efficient chiral chain diene ligands in the rhodium-catalyzed conjugated addition of organoboronic acids to various α,β-unsaturated compounds, achieving the desired chiral adducts with good to excellent yields and ee values.     

Formal enantioselective synthesis of (+)-estrone

A formal total synthesis of (+)-estrone (4% overall yield; ca. 12 steps) could be achieved via the Torgov diene. An asymmetric allylic substitution is the key step for the construction of the chiral quaternary carbon center of a synthetic intermediate which was converted in four steps to the Torgov diene. [reaction: see text]     

Silylcupration of 1,3-dienes followed by an electrophilic trapping reaction

[see reaction]. Silylcupration reaction of 1,3-dienes with a cyanocuprate reagent, PhMe2SiCuCNLi, followed by an electrophilic trapping has been reported for the first time. The use of allylic phosphates as electrophiles resulted in a highly regioselective reaction with overall 1,4-addition of the silyl and allyl moieties across the diene.     

Competitive Silyl–Prins Cyclization versus Tandem Sakurai–Prins Cyclization: An Interesting Substitution Effect

Two different mechanism pathways are observed for the reaction of allylsilyl alcohols 1 and aldehydes in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf). In the case of allylsilyl alcohols without allylic substituents, the reaction gives dioxaspirodecanes, which are the products of a tandem Sakurai–Prins cyclization. In contrast, allylsilyl alcohols with an allylic substituent (R²≠H) selectively provide oxepanes, thus corresponding to a direct silyl–Prins cyclization. Both types of product are obtained with excellent stereoselectivity. Theoretical studies have been performed to obtain some rationalization for the observed stereoselectivity.     

Sulfoxide-directed enantioselective synthesis of functionalized dihydropyrans

[reaction: see text] The highly selective base-promoted cyclization of enantiopure sulfinyl dienols affords allylic sulfinyl dihydropyrans.     

A rapid divergent synthesis of highly substituted delta-lactones

[reaction: see text] Nucleophilic 1,2-addition of (Z)-gamma-silyloxyvinylzinc reagents to ethyl glyoxylate followed by desilylation and cyclization affords 3,6-dihydro-3-hydroxypyran-2-ones in good chemical yields. In situ formation of allylic phosphates followed by reaction with RCu(CN)Li reagents affords substituted 5,6-dihydropyran-2-ones. The parent compound, 3,6-dihydro-3-hydroxypyran-2-one, undergoes allylic phosphate formation, cuprate-mediated allylic substitution, and 1,4-conjugate addition to afford trans-4,5-disubstituted tetrahydropyran-2-ones in a one-pot process.     

Stereoselection in the Prins-pinacol synthesis of acyltetrahydrofurans

[reaction: see text]. Depending upon the nature of the alkene and allylic substituents, acid-promoted rearrangements of acetals derived from anti allylic diols give 12 or stereoisomeric acyltetrahydrofurans 13. Stereoelectronic effects of the allylic substituents and the extent of bonding in the Prins cyclization transition state are central features of a proposed new model for predicting stereoselection in the Prins-pinacol synthesis of acyltetrahydrofurans.     

Facile, efficient, and enantiospecific syntheses of 1,1'-N-linked pseudodisaccharides as a new class of glycosidase inhibitors

This article describes an efficient synthesis of a potent trehalase inhibitor, 1,1'-N-linked pseudodisaccharide 1 (consisting of two valienamines), in 14 steps with an overall yield of 12% and a first synthesis of 2 (consisting of two 2-epi-valienamines) in 15 steps with an overall yield of 24% from (-)-quinic acid. The synthesis involves a stereospecific palladium-catalyzed coupling reaction between an allylic amine and an allylic chloride as the crucial step. The acetonide blocking groups were shown to be the best hydroxyl protecting groups, compatible with the palladium-catalyzed allylic amination reaction that afforded high yields of the 1,1'-N-linked pseudodisaccharides with a minimum amount of an elimination diene side product.     

Toward the total synthesis of methyl isosartortuoate: construction of the backbone of the diene unit

The backbone of diene precursor in the proposed biogenesis of methyl isosartortuoate through a Diels-Alder reaction has been constructed via dehydration to establish the conjugated system; and double cyclization by using Horner-Wittig-Emmons reaction and the chiral epoxy ring opening.     

Catalytic asymmetric synthesis of a 1-deoxy-1,1-difluoro-D-xylulose

[reaction: see text] A new route, of potential strategic importance, to a difluorosugar analogue has been developed. Key steps included a Stille coupling and a highly regio- and enantioselective dihydroxylation of a highly substituted diene. Protecting groups were chosen to enhance the reactivity of the disubstituted allylic fragment in the AD reaction and allow deprotection under orthogonal conditions.     

Stereoselectivity and regioselectivity in the segment-coupling Prins cyclization

The scope of the segment-coupling Prins cyclization has been investigated. The method is outlined in Scheme 1 and involves esterification of a homoallylic alcohol (1), reductive acetylation to give the alpha-acetoxy ether (3), and cyclization on treatment with a Lewis acid to produce a tetrahydropyran (4). Alkene geometries dictate the product configurations, with E-alkenes leading to equatorial substituents and Z-alkenes leading to axial substituents (Table 1). Not unexpectedly, applying the method to allylic alcohols leads to fragmentation rather than a disfavored 5-endo-trig cyclization. Dienols in which one alkene is allylic and the other alkene is homoallylic cyclize efficiently and produce the tetrahydropyrans 49-54, Table 3. Dienols with two homoallylic alkenes cyclize with modest to high regioselectively, generating tetrahydropyrans 40-45, Table 2. The relative rates for cyclization decrease in the order of vinyl > Z-alkene > E-alkene > alkyne. The configurations of the products are consistent with cyclization via a chair conformation, Figure 1. The 2-oxonia Cope rearrangement may be a factor in the regioselectivity of diene cyclizations and in the erosion of stereoselectivity with Z-alkenes. This investigation establishes the stereoselectivity and regioselectivity for a number of synthetically useful segment-coupling Prins cyclizations.