Allylic Reagents Research Articles

Copper-Catalyzed Allylation of Amines with Cyclopropyldiphenylsulfonium Trifluoromethanesulfonate

AbstractCyclopropyldiphenylsulfonium salt, a famous ylide precursor previously extensively employed in the preparation of cyclic compounds, has been successfully utilized as an efficient allylation reagent in this work. The copper-catalyzed reactions of cyclopropyldiphenylsulfonium trifluoromethanesulfonate with amines in the presence of an appropriate ligand provided the N-allylated products in good yields. Aliphatic/aromatic amines and primary/secondary amines were all converted under mild reaction conditions. This protocol was also applicable to N-functionalization of drug molecules, supplying the corresponding N-allylated compounds in satisfactory yields. The reaction, which showed good functional group tolerance with a wide range of substrates and excellent chemoselectivity, offers an interesting method for the synthesis of N-allyl amines.

Allylboronic Esters as Acceptors in Radical Addition, Boron 1,2-Migration, and Trapping Cascades.

Radical 1,3-carboheteroarylation and 1,3-hydroalkylation of allylboronic esters comprising a 1,2-boron shift is reported. Allylboronic esters are generally used in synthesis as allylation reagents, where the boronic ester moiety gets lost. In the introduced cascades, alkylboronic esters are obtained with the boron entity remaining in the product. The carboheteroarylation of the allylboronic esters are conducted without a metal catalyst, and the 1,3-hydroalkylation is achieved using iron catalysis. Both reactions work efficiently under mild conditions.

A mechanistic study on the regioselective Ni-catalyzed methylation–alkenylation of alkyne with AlMe3 and allylic alcohol

The recently reported Ni-catalyzed methylation–allylation of alkynes with allylic alcohols and AlMe3 reagents delivers valuable tetrasubstituted alkene units in a highly regioselective fashion.

Pd-Catalyzed umpolung asymmetric allylic alkylation of hydrazones to vicinal tertiary and quaternary chiral carbon centers

Vicinal tertiary and quaternary chiral carbon centers are constructed with high regio-, diastereo- and enantioselectivities via Pd-catalyzed umpolung asymmetric allylic alkylation of hydrazones with monosubstituted allyl reagents by using Kündig type chiral N-heterocyclic carbene as the ligand.

Palladium-catalyzed decarboxylative O-allylation of phenols with γ-methylidene-δ-valerolactones

A novel palladium-catalyzed decarboxylative O-allylation of phenols was developed, in which a GMDV was found to be an efficient and selective allylation reagent, affording the target allyl phenyl ethers in up to 92% yields.

CoIII-Catalyzed C-H Alkenylation and Allylation with Cyclopropenes via Sequential C-H/C-C Bond Activation.

An atom-economical strategy for the C-H alkenylation and C-H allylation of arenes by employing cyclopropenes as versatile alkenylating and allylating reagents is reported, catalyzed by cobalt. The Co-catalyzed C-H alkenylation process involves sequential C-H and C-C bond cleavage. Under the optimized conditions, broad-ranging alkenylated (hetero)arenes were synthesized with complete (E)-stereoselectivity (up to 91%). The consecutive C-H allylation proved viable under basic conditions via double-bond migration of the initially generated alkenyl (hetero)arenes, thus leading to allylated (hetero)arenes with high stereoselectivity of olefin (E/Z ratio = 91:9 to 100:0).

Palladium-Catalyzed Asymmetric Trifluoromethylated Allylic Alkylation of Pyrazolones Enabled by α-(Trifluoromethyl)alkenyl Acetates

The first asymmetric trifluoromethylated allylic alkylation of pyrazolones using α-(trifluoromethyl)alkenyl acetates as a novel trifluoromethylated allylation reagent is described, affording various functionalized chiral pyrazolones containing a trifluoromethylated allyl substituent in high yields with excellent regio-/enantio-/diastereoselectivities. Mechanistically, the double-bond migration of α-(trifluoromethyl)alkenyl acetates in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene is initial and interesting step. More importantly, this study is of significance in providing a novel and widely applicable trifluoromethyl-containing allylation reagent.

Copper-Catalyzed Highly Enantioselective 1,4-Protoboration of Terminal 1,3-Dienes

Copper-Catalyzed Highly Enantioselective 1,4-Protoboration of Terminal 1,3-Dienes

Mechanistic exploration of Rh(III)-catalyzed C-H allylation of benzamides with allyl bromide

The allylation of various benzamides under the catalysis of transition metal by the C-H activation is an attractive tool for the functionalization of aromatic system. One such reaction under the catalysis of Rh(III)-complex using allyl bromide as the allylating reagent was studied theoretically by employing density functional theory (DFT) to find out the plausible mechanistic path. The metal mediated allylation of various benzamides includes six steps – coordination of substrate with the catalyst, N-H metalation, C-H metalation, addition of allyl bromide, proton transfer and demetalation. Our calculations reveal that, the path involving the insertion of allyl bromide is energetically favorable compared to that of oxidative addition of allyl bromide. The effect of electron withdrawing and electron releasing substituents was also explained which nicely agrees with the experimental report.

1,3-Bifunctional Nucleophilic Allylation Reagents: Preparative Methods and Synthetic Applications

Abstract1,3-Bifunctional nucleophilic allylation reagents play an important role in organic synthesis. In this short review, we summarize the methods for the preparation of 1,3-bifunctional reagents and their reactions with various electrophiles. Synthetic applications of these reagents in the context of complex molecule synthesis are also discussed.1 Introduction2 Reagent Synthesis2.1 Symmetrical Reagents2.2 Unsymmetrical Reagents2.2.1 Bis-silane and Silyl-stannane Reagents2.2.2 Bis-boron and Silyl-boron Reagents3 Synthetic Applications3.1 Allylation of Aldehydes3.2 Allylation of Ketones3.3 Allylation of Imines3.4 Allylation of Other Electrophiles with 1,3-Bifunctional Allylation Reagents4 Summary

Photoredox Allylation Reactions Mediated by Bismuth in Aqueous Conditions

AbstractOrganometallic allylic reagents are widely used in the construction of C−C bonds by Barbier‐type reactions. In this communication, we have described a photoredox Barbier allylation of aldehydes mediated by bismuth, in absence of other metals as co‐reductants. Mild reaction conditions, tolerance of oxygen, and use of aqueous solvent make this photoredox methodology attractive for green and sustainable synthesis of homoallylic alcohols.

Visible‐Light Photoredox‐Catalyzed α‐Allylation of α‐Bromocarbonyl Compounds Using Allyltrimethylsilane

The development of a greener allylation reagent for α‐allylation of carbonyl compounds is of great necessity. Here we present allyltrimethylsilane as a novel allylation reagent in the photoredox‐catalyzed α‐allylation of carbonyl compounds such as ketones, esters, and amides. The reaction process shows good functional group tolerance and generates a good yield of the product. The reaction mechanism is a radical‐mediated reaction by photo‐induced single electron transfer.

C–O cleavage via InIII alkoxide intermediates: In situ 13C NMR analysis of the mechanism of an enantioselective in-mediated cyclopropanation reaction

Abstract The mechanism of asymmetric cyclopropanation of dibenzylideneacetone and benzylideneacetone by in situ generated allyl indium reagents in the presence of methyl mandelate as a chiral modifier has been studied by in situ 13C{1H} NMR in conjunction with 13C/2H labelling and mass spectrometry. Two indium alkoxides were identified, the first arising from indium mediated allylation of the ketone, the second arising from reaction of an in situ liberated homoallylic via a LiI mediated reaction with excess allyl indium reagent. On acidification, protonation at oxygen induces C–O rather than In–O cleavage and the incipient tertiary allylic cation is stereoselectivly allylated with approximately 90% si selectivity, via what is assumed to be a mandelate-chelated indium allyl reagent.

Selective Alkynylallylation of the C−C σ Bond of Cyclopropenes

A Pd-catalyzed regio- and stereoselective alkynylallylation of a specific C-C σ bond in cyclopropenes, using allyl propiolates as both allylation and alkynylation reagents, has been achieved for the first time. By merging selective C(sp2 )-C(sp3 ) bond scission with conjunctive cross-couplings, this decarboxylative reorganization reaction features fascinating atom and step economy and provides an efficient approach to highly functionalized dienynes from readily available substrates. Without further optimization, gram-scale products can be easily obtained by such a simple, neutral, and low-cost catalytic system with high TONs. DFT calculations afford a rationale toward the formation of the products and indicate that the selective insertion of the double bond of cyclopropenes into the C-Pd bond of ambidentate Pd complex and the subsequent nonclassical β-C elimination promoted by 1,4-palladium migration are critical for the success of the reaction.

Selective Alkynylallylation of the C−C σ Bond of Cyclopropenes

AbstractA Pd‐catalyzed regio‐ and stereoselective alkynylallylation of a specific C−C σ bond in cyclopropenes, using allyl propiolates as both allylation and alkynylation reagents, has been achieved for the first time. By merging selective C(sp2)‐C(sp3) bond scission with conjunctive cross‐couplings, this decarboxylative reorganization reaction features fascinating atom and step economy and provides an efficient approach to highly functionalized dienynes from readily available substrates. Without further optimization, gram‐scale products can be easily obtained by such a simple, neutral, and low‐cost catalytic system with high TONs. DFT calculations afford a rationale toward the formation of the products and indicate that the selective insertion of the double bond of cyclopropenes into the C‐Pd bond of ambidentate Pd complex and the subsequent nonclassical β‐C elimination promoted by 1,4‐palladium migration are critical for the success of the reaction.

Copper(I)-catalyzed asymmetric 1,6-conjugate allylation

Catalytic asymmetric conjugate allylation of unsaturated carbonyl compounds is usually difficult to achieve, as 1,2-addition proceeds dominantly and high asymmetric induction is a challenging task. Herein, we disclose a copper(I)-NHC complex catalyzed asymmetric 1,6-conjugate allylation of 2,2-dimethyl-6-alkenyl-4H-1,3-dioxin-4-ones. The phenolic hydroxyl group in NHC ligands is found to be pivotal to obtain the desired products. Both aryl group and alkyl group at δ-position are well tolerated with the corresponding products generated in moderate to high yields and high enantioselectivity. Moreover, both 2-substituted and 3-substituted allylboronates serve as acceptable allylation reagents. At last, the synthetic utility of the products is demonstrated in several transformations by means of the versatile terminal olefin and dioxinone groups.

Base-Promoted C-C Bond Activation Enables Radical Allylation with Homoallylic Alcohols.

The Cα–Cβ bond in homoallylic alcohols can be activated under basic conditions, qualifying these nonstrained acyclic systems as radical allylation reagents. This reactivity is exemplified by photoinitiated (with visible light and/or blue LEDs) allylation of perfluoroalkyl and alkyl radicals generated from perfluoroalkyl iodides and alkylpyridinium salts, respectively, with homoallylic alcohols. C-radical addition to the double bond of the title reagents and subsequent base-promoted homolytic Cα–Cβ cleavage leads to the formation of the corresponding allylated products along with ketyl radicals that act as single electron reductants to sustain the chain reactions. Substrate scope is documented and the role of base in the C–C bond activation is studied by computation.

Stereoselective Syntheses of γ,δ-Bifunctionalized Homoallylic Alcohols and Ethers via Chemoselective Allyl Addition to Aldehydes.

Stereoselective synthesis of γ,δ-bifunctionalized homoallylic alcohols and ethers via chemoselective allylation is reported. Pd-catalyzed 1,2-diboration of allenylsilane provided a novel 1,1,2-trifunctional allylation reagent. Allylboration of aldehydes with the reagent followed by in situ protection gave TES-protected homoallylic alcohols with excellent Z-selectivities. Chemoselective allylsilation with the same reagent delivered γ,δ-bifunctionalized homoallylic ethers with high E-selectivities. The bifunctionalized alkene group in the products underwent various transformations without erosion of the olefin geometry.

Cp*Co(III)-Catalyzed γ-Selective C-H Allylation/Hydroamination Cascade for the Synthesis of Dihydroisoquinolines.

A Cp*Co(III)-catalyzed γ-selective C-H allylation/hydroamination cascade toward the synthesis of 3,4-dihydroisoquinolines (DHIQs) has been successfully developed, starting from NH ketimines and allyl carbonates. Notably, highly efficient and γ-selective C-H allylations were accomplished using γ-substituted allyl reagents, thus overcoming the issues of poor α/γ selectivity and low reactivity of previous transition metal-catalyzed C-H allylations. The stereochemistry of allyl carbonates was a crucial factor, and synthesis of the DHIQs was achieved using (Z)-allyl carbonates.

Labeling and Natural Post-Translational Modification of Peptides and Proteins via Chemoselective Pd-Catalyzed Prenylation of Cysteine.

The prenylation of peptides and proteins is an important post-translational modification observed in vivo. We report that the Pd-catalyzed Tsuji–Trost allylation with a Pd/BIPHEPHOS catalyst system allows the allylation of Cys-containing peptides and proteins with complete chemoselectivity and high n/i regioselectivity. In contrast to recently established methods, which use non-native connections, the Pd-catalyzed prenylation produces the natural n-prenylthioether bond. In addition, a variety of biophysical probes such as affinity handles and fluorescent tags can be introduced into Cys-containing peptides and proteins. Furthermore, peptides containing two cysteine residues can be stapled or cyclized using homobifunctional allylic carbonate reagents.