Allylic Nucleophilic Substitution Research Articles

A One-Pot Domino Reaction Providing Fluorinated 5,6-Dihydro-1,2-thiazine 1-Oxides from Sulfoximines and 1-Trifluoromethylstyrenes.

N-Trifluoroacetylated (N-TFA) sulfoximines react with 1-trifluoromethylstyrenes in a one-pot domino reaction to give fluorinated 5,6-dihydro-1,2-thiazine 1-oxides in good to high yields. The process involves three sequential reaction steps that can be characterized as (1) nucleophilic allylic substitution (SN2'), (2) hydrolysis, and (3) intramolecular nucleophilic vinylic substitution (SNV). The products can further be modified by defluorination. The molecular structure of the resulting product was confirmed by X-ray crystallographic analysis.

Water promoted allylic nucleophilic substitution reactions of (E)-1,3 diphenylallyl acetate

A transition metal free, reagent free, only water based, greener protocol for the allylic alkylation, allylic amination, and O-allylation of (E)-1,3-diphenylallyl acetate is described.

Direct palladium-catalyzed allylic alkylations of alcohols with enamines: Synthesis of homoallyl ketones

An efficient, direct nucleophilic allylic substitution of α-, β- and γ-substituted alcohols with enamines, using the Pd(OAc)2/PPh3 catalyst system and ZnBr2 as a promoter in CH2Cl2 at reflux, is reported. The reaction course was dependent on the steric hindrance at the α- or γ-positions with respect to the functionalized α-carbon, selectively affording in moderate to good yields, α- or γ-homoallyl ketones, the so-called “linear” and “branched” products, respectively.

Palladium-catalyzed nucleophilic allylic substitution of Morita–Baylis–Hillman adducts with enamines: Synthesis of 1,5-dicarbonyl compounds

An efficient nucleophilic allylic substitution of a variety of Morita–Baylis–Hillman adducts with enamines catalyzed by Pd(OAc) 2 in the presence of ZnBr 2 as a promoter is described in the present study. The reaction gives S N 2-type 1,5-dicarbonyl compounds that may subsequently undergo an intramolecular conjugate addition onto the enone moiety affording the corresponding 1,4-adducts. All the synthesized compounds have been isolated in moderate to good yields and fully characterized.

Transition-metal-free nucleophilic allylic substitutions of Morita–Baylis–Hillman bromides with aliphatic and aromatic amines

ABSTRACTA simple protocol for the preparation of functionalized allylic amines under mild, transition-metal-free conditions from the reaction of Morita–Baylis–Hillman (MBH) bromides with amines is described herein. The treatment of the MBH bromides with various amines in the presence of NaI and Et3N in aqueous acetone solution and at room temperature affords the corresponding functionalized allyl amines in moderate to good yields (45–87%). The reaction is rapid and carried out at room temperature.

ChemInform Abstract: Synthesis of a Series of γ‐Keto Allyl Phosphonates.

AbstractCyclic Morita—Baylis—Hillman acetates are rapidly transformed into the corresponding γ‐keto allyl phosphonates by allylic nucleophilic substitution.

Synthesis of a Series of γ-Keto Allyl Phosphonates.

Under solvent-free conditions and at 80 °C, a DMAP- or imidazole-mediated clean and rapid conversion of cyclic Morita-Baylis-Hillman (MBH) acetates into the corresponding γ-keto allyl phosphonates in 70-93% yields is described herein. This allylic nucleophilic substitution works well with primary and secondary acetates bearing, at the β'-position, linear or branched alkyl groups and aryl groups.

Synthesis of fatty acid conjugates with phenols, carbohydrates, amines, and CH‐acidic compounds by Pd(0)‐catalyzed allylic substitution

The efficiency of a pharmaceutical can be increased by connecting it to a fatty acid. Nucleophilic allylic substitution of methyl 10‐undecenoate and methyl oleate with palladium(0) as catalyst is explored to see, whether this reaction is useful for such connections with regard to yield and selectivity. For that purpose the allylic CH‐bonds in methyl 10‐undecenoate and methyl oleate were oxidized with selenium dioxide and tert‐butylhydroperoxide. The obtained allylic alcohols were then activated by conversion into their methyl carbonates. Allylic substitution was performed with O‐nucleophiles as methanol, carbohydrates, and different phenols as α‐tocopherol and estradiol; furthermore N‐ and C‐nucleophiles were applied. The yields of substitution products were in the range of 37–98%. High yields of conjugates were obtained with phenols, even when the hydroxy group was sterically shielded. These conjugates have an ether bond, a CN or a CC bond as link. They should have the advantage to be more stable in body fluids than the frequently applied conjugates being connected by the less inert ester bond. Triesters and dicyanoesters obtained with C‐nucleophiles can be possibly used as cross linkers for polyesters and polyamides.Practical applications: These conjugates should be more stable in cells and body fluids than the frequently applied conjugates being connected by the less inert ester bond. Triesters and dicyanoesters obtained with C‐nucleophiles can be possibly used as cross linkers for polyesters and polyamides.Methyl 9‐hydroxy‐10‐undecenoate is prepared by allylic oxidation from methyl 10‐undecenoate. After esterification to the methyl carbonate this leaving group is substituted via Pd(0)‐catalysis by O‐, N‐, and C‐nucleophiles to afford fatty acid conjugates. Similarly methyl oleate is converted.

Hydrogen Bond Controlled Anti‐Aza‐Michael Addition: Diastereoselective Synthesis of Cyclobutene‐Containing Amino Acid Derivatives

AbstractThe chemical reactivity encoded in a highly substituted cyclobutane platform, which contains the (E,E)‐dimethyl 2,2′‐(cyclobutane‐1,2‐diylidene)diacetate structural motif, has been explored. The cyclobutane platform features a C2 axis of symmetry as well as a dense and interconnected ring functionalization pattern that is defined by two allylic/benzylic stereogenic oxygen‐containing quaternary centers with a 1,2‐trans configuration and two exocyclic acrylate chains. The reactivity profile of the cyclobutane platform is defined by two important kinetic barriers (steric strain and antiaromaticity) and two structure‐biased chemical processes: (1) the thermally‐driven [3,3] sigmatropic rearrangement between one of the two equivalent aryloates and the corresponding allylic acrylate chain and (2) the allylic nucleophilic substitution (SN2′ reaction) that involves a tertiary aryloate and its exocyclic double bond (anti‐Michael addition). The reaction of platform 3a with secondary amines delivered the corresponding cyclobutene amino acid derivatives 15a–15f in excellent yields (up to ≥95 %) and high diastereoselectivities (up to 99:1). Computational studies are described to rationalize the observed diastereoselectivity.

A recyclable palladium-catalyzed synthesis of 2-methylene-2,3-dihydrobenzofuran-3-ols by cycloisomerization of 2-(1-hydroxyprop-2-ynyl)phenols in ionic liquids.

A recyclable palladium-catalyzed synthesis of 2-methylene-2,3-dihydrobenzofuran-3-ols 2 by heterocyclization of 2-(1-hydroxyprop-2-ynyl)phenols 1 in an ionic liquid medium (BmimBF4) is presented. The process takes place under relatively mild conditions (100 °C, 5 h) in the presence of catalytic amounts (2 mol %) of PdI2 in conjunction with KI (5 equiv with respect to PdI2) and an organic base, such as morpholine (1 equiv with respect to 1), to give 2 in high yields (70%–86%). The PdI2-KI catalytic system could be recycled up to six times without appreciable loss of activity. Moreover, products 2 could be easily converted in a one-pot fashion into 2-hydroxymethylbenzofurans 3 (52%–71%, based on 1) and 2-methoxymethylbenzofurans 4 (52%–80%, based on 1) by acid-catalyzed allylic isomerization or allylic nucleophilic substitution.

ChemInform Abstract: Enantioselective Synthesis of 4‐Heterosubstituted Cyclopentenones.

AbstractA highly effective palladium‐catalyzed kinetic resolution procedure via nucleophilic allylic substitutions is presented.

One Pot Continuous Reaction of Benzoin Condensation and Allylic Nucleophilic Substitution Using N-Heterocyclic Carbenes and Nickel(Ⅱ) Chloride as Catalysts

With the presence of nickel(Ⅱ) chloride as metal complex catalyst and N-heterocyclic carbene as organic catalyst effective one pot synthesis of allylated α-hydroxy carbonyl compound in 78% yield was developed using benzaldehyde and cinnamyl acetate as precursors in potassium carbonate THF solution.The involved reactions during the continuous reaction are benzoin condensation and allylic nucleophilic substitution.

Enantioselective Synthesis of 4-Heterosubstituted Cyclopentenones

Racemic 4-hydroxycyclopentenone, readily derived from furfuryl alcohol, can be transformed via its O-Boc derivative to 4-acyloxy, 4-aryloxy-, 4-amino-, or 4-thio-substituted cyclopentenones with high enantioselectivity by palladium-catalyzed kinetic resolution via nucleophilic allylic substitutions. Applying this methodology, a short formal synthesis of ent-noraristeromycin was readily accomplished.

Stepwise catalytic transformations of renewable feedstock arising from plant oils

AbstractTwo synthetic approaches to produce functionalized plant oil derivatives were investigated. The ruthenium‐catalyzed ene‐yne cross‐metathesis of propargylic carbonates with terminal olefins arising from ethenolysis of methyl oleate provides conjugated dienes. It was shown that the reactivity of these dienes in Diels–Alder [4 + 2]‐cycloaddition with symmetrical electron‐deficient alkynes towards the formation of cyclohexadienes was effective but limited by stereochemical considerations. On the other hand, the stepwise ene‐yne cross‐metathesis followed by ruthenium‐catalyzed nucleophilic allylic substitution by O, N, and C‐nucleophiles was very efficient both in term of reactivity and regioselectivity.

ChemInform Abstract: A New Copper(I)‐Catalyzed Cycloetherification/Acid‐Catalyzed Allylic Nucleophilic Substitution for One‐Pot Synthesis of 2‐Substituted Benzofurans.

AbstractThe cycloetherification process affords alkylidene‐substituted dihydrobenzofuran structures.

A New Copper(I)-Catalyzed Cycloetherification/Acid-Catalyzed Allylic Nucleophilic Substitution for One-Pot Synthesis of 2-Substituted Benzofurans

A new copper(I)-catalyzed cycloetherification followed by an acid-catalyzed allylic nucleophilic substitution have been developed for the one-pot synthesis of 2-substituted benzofurans. This one-pot reaction proceeds efficiently under extremely mild conditions with simple and inexpensive catalysts, providing diversely substituted benzofurans in good to excellent yields.

Transition metal catalyzed nucleophilic allylic substitution: activation of allylic alcohols via π-allylic species

Modern organic synthesis now requires efficient atom economical synthetic methods operating under greener pathways to achieve C-C and C-heteroatom bond formation. Direct activation of allylic alcohols in the presence of transition metal catalysts leading to electrophilic π-allyl metal intermediates represents such a promising target in the field of nucleophilic allylation reactions. During the last decade, this topic of recognized importance has become an emerging area, and selected transition metals, sometimes associated with alcohol activators, have brought elegant solutions for performing allylic substitution directly from alcohols in a regio, stereo and enantioselective manner.

Nucleophilic substitution reaction of Morita–Baylis–Hillman adducts of isatin with X, S, N, and O-nucleophiles: a facile and efficient synthesis of highly functionalized tetrasubstituted alkene appended oxindoles

The Morita–Baylis–Hillman adducts derived from isatins and maleimides have undergone a facile and efficient allylic nucleophilic substitution reaction with X, S, N, and O-nucleophiles to afford functionalized tetrasubstituted alkene appended oxindoles in very good yield. The MBH adducts and their acetates on treatment with halides, saturated and unsaturated amines, thiols, and trialkyl orthoformates afforded allyl halide, allyl amine, allyl thio-ether and allyl ether derivatives of oxindole, respectively.

Preparation of chiral ruthenium(iv) complexes and applications in regio- and enantioselective allylation of phenols

Facile preparations of chiral [Ru(Cp*)]- and [Ru(Cp')]-based allyl complexes featuring N,O chelate derived from (+)-nopinone are described. Single crystal X-ray structural analysis of one complex revealed the preferential configuration of the ruthenium centre and the orientation of the unsymmetrical allylic substituent. Applications of these complexes in catalysis for nucleophilic allylic substitution allowed regio- and enantioselective formation of branched allyl ethers from phenols.

ChemInform Abstract: The Allylic Nucleophilic Substitution of Morita—Baylis—Hillman Acetates with Isocyanides: A Facile Synthesis of Trisubstituted Olefins.

AbstractOptimized conditions allow a clean reaction of the title acetates with TosMIC.