Copper-catalyzed Allylic Substitution Research Articles

Synthesis of the C(1)-C(13) Fragment of Leiodermatolide via Hydrogen-Mediated C-C Bond Formation.

The C(1)–C(13) fragment of the antimitotic marine macrolide leiodermatolide is prepared in seven steps via hydrogenative and transfer-hydrogenative reductive C–C couplings. A hydrogen-mediated reductive coupling of acetylene with a Roche-type aldehyde is used to construct C(7)–C(13). A 2-propanol-mediated reductive coupling of allyl acetate with (E)-2-methylbut-2-enal at a low loading of iridium (1 mol %) is used to construct C(1)–C(6), which is converted to an allylsilane using Oestereich’s copper-catalyzed allylic substitution of Si–Zn reagents. The union of the C(1)–C(6) and C(7)–C(13) fragments is achieved via stereoselective Sakurai allylation.

Synthesis of Branched Alkylboronates by Copper‐Catalyzed Allylic Substitution Reactions of Allylic Chlorides with 1,1‐Diborylalkanes

AbstractReported herein is a copper‐catalyzed SN2′‐selective allylic substitution reaction using readily accessible allylic chlorides and 1,1‐diborylalkanes, a reaction which proceeds with chemoselective C−B bond activation of the 1,1‐diborylalkanes. In the presence of a catalytic amount of [Cu(IMes)Cl] [IMes=1,3‐bis(2,4,6‐trimethylphenyl)imidazole‐2‐ylidene] and LiOtBu as a base, a range of primary and secondary allylic chlorides undergo the SN2′‐selective allylic substitution reaction to produce branched alkylboronates. The synthetic utilities of the obtained alkylboronates are also presented.

ChemInform Abstract: Copper‐Catalyzed Allylation of α,α‐Difluoro‐Substituted Organozinc Reagents.

A method for the coupling of organozinc reagents, difluorocarbene, and allylic electrophiles is described. The reaction involves insertion of difluorocarbene into the carbon–zinc bond followed by copper-catalyzed allylic substitution.

Silylative cyclopropanation of allyl phosphates with silylboronates.

A potassium-bis(trimethylsilyl)amide-mediated cyclopropanation of allyl phosphates with silylboronates has been developed. Unlike the reported copper-catalyzed allylic substitution reactions, the nucleophile selectively attacks at the β-position of the allylic substrates under the present reaction conditions. The mechanism of this process has also been investigated, thus indicating the involvement of a silylpotassium species as the active nucleophilic component.

Copper-Catalyzed Allylation of α,α-Difluoro-Substituted Organozinc Reagents

A method for the coupling of organozinc reagents, difluorocarbene, and allylic electrophiles is described. The reaction involves insertion of difluorocarbene into the carbon-zinc bond followed by copper-catalyzed allylic substitution.

Copper-Catalyzed Allylic Substitution and Conjugate Addition with Alkylboranes

Copper-Catalyzed Allylic Substitution and Conjugate Addition with Alkylboranes

Catalytic asymmetric synthesis of chromenes and tetrahydroquinolines via sequential allylic alkylation and intramolecular Heck coupling

Highly enantioselective synthesis of chiral chromenes and tetrahydroquinolines is achieved by combining asymmetric copper-catalyzed allylic substitution with Grignard reagents and an efficient intramolecular Heck reaction. Moreover, the exocyclic double bond formed in the cyclisation was subjected to RCM, hydroboration and hydrogenation illuminating the synthetic versatility of these heterocycles.

Asymmetric Allylic Alkylation in Combination with Ring-Closing Metathesis for the Preparation of Chiral N-Heterocycles

Asymmetric copper-catalyzed allylic substitution with methylmagnesium bromide is employed in combination with ring-closing olefin metathesis or ene-yne metathesis to achieve the synthesis of chiral, unsaturated nitrogen heterocycles. The resulting six- to eight-membered chiral heterocycles are accessible in high yields and with excellent enantioselectivities.

Enantioselective Synthesis of α-Methyl Carboxylic Acids from Readily Available Starting Materials via Chemoenzymatic Dynamic Kinetic Resolution

An enantioselective method for the synthesis of α-methyl carboxylic acids starting from trans-cinnamaldehyde, a readily available and inexpensive compound, has been developed. Allylic alcohol 1 was obtained via a standard Grignard addition to trans-cinnamaldehyde. Dynamic kinetic resolution was applied to allylic alcohol 1 utilizing a ruthenium catalyst and either an (R)-selective lipase or an (S)-selective protease to provide the corresponding allylic esters in high yield and high ee. A copper-catalyzed allylic substitution was then applied to provide the corresponding alkenes with inversion of stereochemistry. Subsequent C-C double bond cleavage afforded pharmaceutically important α-methyl substituted carboxylic acids in high ee and overall yields of up to 76%.

An Enantioselective Route to α-Methyl Carboxylic Acids via Metal and Enzyme Catalysis

Dynamic kinetic resolution of allylic alcohols to allylic acetates followed by copper-catalyzed allylic substitution gave alkenes in high yields and high optical purity. Subsequent oxidative C-C double bond cleavage afforded pharmaceutically important alpha-methyl substituted carboxylic acids in high ee.

O‐DPPB‐Directed Copper‐Mediated and ‐Catalyzed Allylic Substitution with Grignard Reagents

The ortho-diphenylphosphanylbenzoyl (o-DPPB) group was explored as a directing leaving group in copper-mediated and copper-catalyzed allylic substitution with Grignard reagents. Complete control of chemo-, regio- and stereoselectivity with complete syn-1,3-chirality transfer was observed as a result of the directed nature of the reaction. No excess of organometallic reagent is required and the directing group can be recovered quantitatively. Coordination studies in the solid state and in solution have shown that two substrates are bound via the phosphine function of the directing group at copper. Dynamic NMR experiments in solution are in agreement with a ligand-exchange process at copper, a prerequisite for the development of a substoichiometric process.

Catalytic Epoxypolyene Cyclization via Radicals: Highly Diastereoselective Formal Synthesis of Puupehedione and 8-epi-Puupehedione

Abstract: A catalytic and highly stereoselective synthesis of a com-mon building block for the marine natural product puupehedione ( 1 )and its biologically more active 8-epimer is described. Our ap-proach features a copper-catalyzed allylic substitution reaction ofepoxyfarnesyl acetate and a diastereoselective titanocene-catalyzedepoxypolyene cyclization via radicals. The formal syntheses of 1 and 2 are completed by highly diastereoselective ring closures to therequired benzodihydropyran units. Key words: catalysis, cuprates, epoxypolyene cyclization, naturalproducts Many biologically active compounds, some of them ofmarine origin, are composed of sesquiterpene units linkedto phenolic structures. 1 Prominent examples includepuupehedione ( 1 ), 2a its 8-epimer 2 , 2b and numerousderivatives with varying oxidation patterns on the arenemoiety. 3 They possess important biological properties,e.g. antitumor, 4 antiviral, 5 and antibiotic activities. 6 Over the last years the radical chemistry originating fromtitanocene-catalyzed epoxide opening has attracted a greatdeal of attention.

Practical Synthesis of Allylic Silanes from Allylic Esters and Carbamates by Stereoselective Copper-Catalyzed Allylic Substitution Reactions

The first copper-catalyzed allylic substitution reactions of allylic acetates and carbamates employing a bis(triorganosilyl)zinc reagent are reported. This novel procedure avoids the use of stoichiometric amounts of copper salts which are usually mandatory with this chemistry. Application of this methodology to standard model substrates substantiates a high diastereoselectivity for the double bond geometry (E : Z) as well as the relative configuration (syn : anti).

Synthesis and Use of a Phosphoramidite Ligand for the Copper-Catalyzed Enantioselective­ Allylic Substitution. Tandem Allylic Substitution/Ring-Closing­ Metathesis

A new one-pot method of reductive amination is used to prepare a chiral C2 symmetrical amine. This amine is used for the synthesis of a new chiral phosphoramidite ligand. The new ligand is, in turn, used to illustrate the enantioselective copper-catalyzed allylic substitution with Grignard reagents. When a remote double bond is located on the Grignard reagent, the newly formed alkene undergoes an in situ ruthenium-catalyzed ring-closing metathesis to afford the cyclized product in 77% yield and 94% ee.