Synthesis of allenes via palladium-catalyzed hydrogen-transfer reactions: propargylic amines as an allenyl anion equivalent

Synthesis of allenes has been achieved by using palladium-catalyzed hydrogen-transfer reactions. Various propargylic amines, which were readily prepapred from iodobenzenes and propargylic amines by Sonogashira coupling reaction, underwent the hydrogen-transfer reaction in the presence of Pd2dba3.CHCl3/(C6F5)3P catalyst at 100 degrees C in dioxane for 24 h, giving the corresponding allenes in 43-99% yields. Various propargylic alcohols containing a propargylic aminomethyl group, synthesized by the addition of lithium acetylides of N,N-diisopropylprop-2-ynylamine to aldehydes and a ketone, also underwent the hydrogen-transfer reaction in the presence of Pd2dba3.CHCl3 catalyst and (C6F5)3P at 80 degrees C in dioxane, giving the corresponding allenes in 56-92% yields. In the current transformation, propargylic amines can be handled as an allenyl anion equivalent and introduced into various electrophiles to be transformed into allenes under palladium-catalyzed conditions.     

Direct and stereospecific synthesis of allenes via reduction of propargylic alcohols with Cp2Zr(H)Cl

Allenes can be synthesized via the direct SN2' addition of hydride to propargylic alcohols. Previous examples of this approach, however, have involved harsh reaction conditions and have suffered from incomplete transfer of central chirality to axial chirality. Here we show that Cp2Zr(H)Cl can react with the zinc or magnesium alkoxides of propargylic alcohols to generate allenes in good yield and in high optical purity. Dialkyl-, alkyl-aryl-, and diaryl-allenes are accessible by this method. Furthermore, the reaction can provide silyl-substituted allenes, trisubstituted allenes, and terminal allenes.     

Palladium(0)-catalyzed synthesis of chiral ene-allenes using alkenyl trifluoroborates

Enantioenriched allenes serve as chiral transfer reagents, making them attractive synthetic targets. Herein, the synthesis of enantioenriched allenes utilizing a Pd(0)-catalyzed cross-coupling reaction of propargylic carbonates and phosphates with alkenyl trifluoroborates is reported. Di-, tri-, and tetrasubstituted allenes were synthesized in moderate to high optical yields. Several racemic allenes possessing various functional groups were also synthesized.     

Enantiospecific synthesis of 1,3-disubstituted allenes by palladium-catalyzed coupling of propargylic compounds with arylboronic acids

An enantiospecific coupling of propargylic esters and carbonates with arylboronic acids has been developed using a palladium catalyst. Optically active 1,3-disubstituted allenes were synthesized with high enantiomeric excesses by carrying out the reactions under basic aqueous conditions.     

General approach to allenes through copper-catalyzed γ-selective and stereospecific coupling between propargylic phosphates and alkylboranes

Copper-catalyzed γ-selective coupling between propargylic phosphates and alkylboron compounds (alkyl-9-BBN, prepared by hydroboration of alkenes with 9-BBN-H) affords multisubstituted allenes with various functional groups. The reaction of enantioenriched propargylic phosphates to give axially chiral allenes proceeds with excellent point-to-axial chirality transfer with 1,3-anti stereochemistry.     

Rh‐Catalyzed Reaction of Propargylic Alcohols with Aryl Boronic Acids–Switch from β‐OH Elimination to Protodemetalation

It is known that Rh‐catalyzed reaction of propargylic alcohols with aryl metallic reagents undergoes S_N2’‐type reaction affording allenes via a sequential arylmetalation and β‐OH elimination process. Here we report a Rh/Ag‐cocatalyzed reaction of propargylic alcohols with organoboronic acids affording stereo‐defined (E)‐3‐arylallylic alcohols via arylmetalation and protodemetalation with a high regio‐ and stereoselectivity under very mild conditions. The reaction exhibits a good substrate scope and the compatibility with synthetically useful functional groups with no racemization for optically active propargylic alcohols. Such a reaction may also be extended to homopropargylic alcohols with a remarkable regioselectivity and exclusive E‐stereoselectivity.     

Synthesis of conjugated allenes through copper-catalyzed γ-selective and stereospecific coupling between propargylic phosphates and aryl- or alkenylboronates

A Cu-catalyzed γ-selective coupling reaction between propargylic phosphates and aryl- or alkenylboronates afforded aryl- or alkenyl-conjugated allenes. The reaction showed excellent functional group compatibility in both the propargylic substrates and the boronates. The reaction of an enantioenriched propargylic phosphate proceeded with excellent chirality transfer with 1,3-anti stereochemistry to give axially chiral aryl- and alkenylallenes.     

Palladium‐Catalyzed Coupling of Propargylic Alcohols with Boronic Acids under Ambient Conditions

A highly efficient palladium‐catalyzed direct coupling of propargylic alcohols with organoboronic acids to synthesize tri‐ and tetra‐substituted allenes has been developed under mild reaction conditions. Many useful functional groups are tolerated in this process with high to excellent yields. Preliminary biological studies showed that several tri‐ and tetra‐substituted allenes exhibited potent anti‐diabetic activities.     

Synthesis of allenes via gold-catalyzed intermolecular reaction of propargylic alcohols and aromatic compounds

Functionalized allenes are efficiently synthesized in moderate to high yield from gold-catalyzed intermolecular reaction of propargylic alcohols and aromatic compounds. The user-friendly process could be conducted under mild reaction conditions with easily accessible starting materials.     

Asymmetric synthesis of trisubstituted allenes: copper-catalyzed alkylation and arylation of propargylic phosphates

Asymmetric synthesis of trisubstituted allenes is accomplished by copper-catalyzed alkylation and arylation of propargylic phosphates using organoboron nucleophiles. Excellent chirality transfer and regioselectivity, together with good functional group compatibility, were observed in reactions with both alkyl boranes and arylboronic esters.     

Synthesis of mono- and 1,3-disubstituted allenes from propargylic amines via palladium-catalysed hydride-transfer reaction

Mono- and 1,3-disubstituted allenes were synthesized from the corresponding propargylamines via palladium-catalysed hydride-transfer reaction. In the current transformation, propargylic amines can be handled as allenyl anion equivalents and introduced into various electrophiles to be transformed into allenes under palladium-catalyzed conditions.     

Ruthenium-catalyzed two-component addition to form 1,3-dienes: optimization, scope, applications, and mechanism.

A two component coupling of an allene and an activated olefin to form 1,3-dienes has been developed. The requisite allenes are synthesized either from terminal alkynes by a one carbon homologation using copper(I) iodide, paraformaldehyde, and diisopropylamine, via an ortho ester-Claisen rearrangement from a propargylic alcohol, or via a Wittig type reaction on a ketene generated in situ from an acid chloride. Mono- through tetrasubstituted allenes could be synthesized by these methods. Either cyclopentadienylruthenium(II) cyclooctadiene chloride or cyclopentadienylruthenium(II) trisacetonitrile hexafluorophosphate catalyze the addition reaction. When the former catalyst is employed, an alkyne activator is added to help generate the active catalyst. Through systematic optimization studies, a range of conditions was examined. The optimal conditions consisted of the use of cerium(III) trichloride heptahydrate as a cocatalyst in dimethylformamide as a solvent at 60 degrees C. The reaction was found to be chemoselective, and a wide range of functionality was tolerated, including esters, alcohols, nitriles, and amides. When substituted allenes are used, good selectivity can be obtained with proper substitution. A mechanism involving a ruthenacycle is proposed to account for the selectivity or lack thereof in product formation. With disubstituted allenes, selectivity is obtained when beta-hydrogen elimination is favored from a specific site. In tri- and tetrasubstituted allenes, steric issues concerning the C-C bond forming event appear to be the dominant factor in determining product formation. This process represents a highly atom-economical synthesis of 1,3-dienes in a controlled fashion. The utility of the 1,3-diene products was demonstrated by their use in Diels-Alder reactions to form a variety of cyclic systems including polycyclic structures. This sequence represents a convergent atom economic method for ring formation by a series of simple additions.     

On the lithium dimethylcuprate induced conversion of propargylic esters into allenes using a steroidal C/D fragment derived from vitamin D3 as a stereochemical probe.

The reactions of (CH₃)₂CuLi with various C-8 epimeric propargylic esters derived from Grundmann's ketone, a C/D steroid fragment originating from vitamin D₃, lead to the corresponding allenes, the stereochemistry of which indicate a preferred $\text{anti}$ 1,3-substitution.     

Gold(I)-catalyzed propargyl Claisen rearrangement

Homoallenic alcohols are prepared from propargyl vinyl ethers using a trinuclear gold(I)-oxo complex, [(Ph3PAu)3O]BF4, as a catalyst for propargyl Claisen rearrangement at room temperature. The gold(I)-catalyzed reaction is effective for a diverse collection of propargyl vinyl ethers, including substrates containing aryl and alkyl groups at the propargylic position, and hydrogen, aryl, and alkyl substituents at the alkyne terminus. Tertiary propargyl vinyl ethers can be employed in the reaction, at slightly elevated temperatures, to afford tetrasubstituted allenes. Importantly, the rearrangement of 1,2-disubstituted vinyl ethers proceeds with excellent diastereoselectivity, and the rearrangement of chiral nonracemic propargyl vinyl ethers proceeds with excellent chirality transfer to furnish enantioenriched allenes.     

Highly stereoselective synthesis of tertiary propargylic centers and their isomerization to enantiomerically enriched allenes

Center of attention: A new approach for the synthesis of enantiomerically enriched allenes by isomerization of 2-p-tolylsulfinylphenyl propargylic derivatives is presented, which in turn are prepared by reaction of sulfinylated lithium benzylcarbanions with arylsulfonylacetylenes. The high control of stereoselectivity in both steps is exerted by the sulfinyl group.     

Palladium-catalyzed reduction of propargylic acetates with SmI2. A mild and convenient method for the preparation of allenes

A highly regioselective reduction of propargylic acetates has been attained by using SmI₂ and catalytic Pd(0) in the presence of 2,4-dimethyl-3-pentanol affording various types of allenes in high yields.     

Biocatalytic Synthesis of Allylic and Allenyl Sulfides through a Myoglobin‐Catalyzed Doyle–Kirmse Reaction

The first example of a biocatalytic [2,3]‐sigmatropic rearrangement reaction involving allylic sulfides and diazo reagents (Doyle–Kirmse reaction) is reported. Engineered variants of sperm whale myoglobin catalyze this synthetically valuable C?C bond‐forming transformation with high efficiency and product conversions across a variety of sulfide substrates (e.g., aryl‐, benzyl‐, and alkyl‐substituted allylic sulfides) and α‐diazo esters. Moreover, the scope of this myoglobin‐mediated transformation could be extended to the conversion of propargylic sulfides to give substituted allenes. Active‐site mutations proved effective in enhancing the catalytic efficiency of the hemoprotein in these reactions as well as modulating the enantioselectivity, resulting in the identification of the myoglobin variant Mb(L29S,H64V,V68F), which is capable of mediating asymmetric Doyle–Kirmse reactions with an enantiomeric excess up to 71 %. This work extends the toolbox of currently available biocatalytic strategies for the asymmetric formation of carbon–carbon bonds.     

Complementary Iron(II)‐Catalyzed Oxidative Transformations of Allenes with Different Oxidants

Substituent‐ and oxidant‐dependent transformations of allenes are described. Given the profound influence of the substituent on the reactivity of allenes, the subtle differences in allene structures are manifested in the formation of diverse products when reacted with different electrophiles/oxidants. In general, reactions of nonsilylated allenes involve an allylic cation intermediate by forming a C?O bond, at the sp‐hybridized C2, with either DDQ (2,3‐dichloro‐5,6‐dicyano‐p‐benzoquinone) or TBHP (tert‐butyl hydroperoxide), along with FeCl₂?4 H₂O (10 mol %). In contrast, silylated allenes favor the formation of propargylic cation intermediates by transferring the allenic hydride to the oxidant, thus generating 1,3‐enynes (E1 product) or propargylic THBP ethers (S_N1 product). The formation of these different putative cationic intermediates from nonsilylated and silylated allenes is strongly supported by DFT calculations.     

Palladium(O)-promoted synthesis of functionally substituted allenes by means of organozinc compounds

The paper describes new routes to aryl-, vinyl-, and 1-alkynylallenes and to diallenes $\text{via}$ Pd(PPh₃)₄-promoted reaction of propargylic or allenic halides with appropriate organozinc halides. Propargylic acetates are also suited to prepare such allenes.     

Palladium-catalyzed synthesis of allenes.

Substituted allenes are selectively obtained in good yields from the reaction of Grignard reagents with propargylic or allenic halides in the presence of catalytic amounts of palladium chloride, triphenylphosphine and diisobutyl aluminum hydride, in tetrahydrofuran at room temperature.