Palladium‐Catalyzed Allylic Alkylation of Doubly Deprotonated Carboxylic Acids

Doubly deprotonated carboxylic acids undergo smooth palladium‐catalyzed carbon alkylations with the allylic substrates methyl allyl carbonate and (E)‐methyl (pent‐3‐en‐2‐yl) carbonate to give γ,δ‐unsaturated carboxylic acids. A diastereoselective and enantioselective protocol leads to (2S,3R)‐hexenoic acid in 87% ee.     

Copper‐Mediated and ‐Catalyzed o‐DPPB‐Directed Allylic Substitution

Complete control of chemo‐, regio‐ and stereoselectivity in the course of copper‐catalyzed and ‐mediated allylic substitution could be obtained with the ortho‐diphenylphosphanyl (o‐DPPB) function as a reagent‐directing leaving group. Complete chirality transfer by way of a syn‐addition process has been achieved for cyclic and acyclic systems. Readily available Grignard reagents may be employed as nucleophiles and the directing o‐DPPB group can be recovered quantitatively. The reaction requires neither cooling nor an excess of organometallic reagent.     

Application of SDP Ligands for Pd‐Catalyzed Allylic Alkylation

Chiral spiro diphosphines (SDP) are efficient ligands for the Pd‐catalyzed asymmetric allylic alkylation of 1,3‐diphenyl‐2‐propenyl acetate with dimethyl malonate and related nucleophiles. The newly synthesized ligand DMM‐SDP ( 1e ) with 3,5‐dimethyl‐4‐methoxy groups on the P‐phenyl rings of the phosphine shows the highest enantioselectivity (up to 99.1% ee). Diethylzinc as a base is critical for obtaining high enantioselectivity in the allylic alkylation using β‐dicarbonyl nucleophiles. The structure of catalyst [PdCl₂((S)‐SDP)] was determined by single crystal X‐ray diffraction. The SDP ligands create an effective asymmetric environment around the palladium, resulting in high enantioselectivities for the asymmetric allylic alkylation reaction     

Palladium‐Catalyzed Stereospecific Allylation of Nitroacetates with Enantioenriched Primary Allylic Amines

An unprecedented stereospecific allylation reaction of nitroacetates with enantioenriched primary allylic amines has been developed. A range of nitroacetates smoothly underwent allylation with enantioenriched primary allylic amines in the presence of a palladium catalyst and boric acid followed by one‐pot decarboxylation to afford structurally diverse homoallylic nitro compounds in good to excellent yields with excellent retention of configuration. On the other hand, the allylation followed by denitronation provided a facile synthetic route to optically active β‐chiral γ,δ‐unsaturated esters.

     

New Highly Effective Phosphite‐Phosphoramidite Ligands for Palladium‐Catalysed Asymmetric Allylic Alkylation Reactions

We have designed a new family of readily available highly‐modular phosphite‐phosphoramidite ligands for asymmetric allylic alkylation reactions. The introduction of a phosphoramidite moiety in the ligand design is highly advantageous in the product outcome. Thus, this ligand series affords high reaction rates and enantioselectivities and, at the same time, shows a broad scope for disubstituted hindered and unhindered substrate types.     

Highly Enantioselective Copper‐Catalyzed Allylic Alkylation with Phosphoramidite Ligands

New phosphoramidites were applied as chiral ligands in the Cu‐catalyzed allylic alkylation with dialkylzinc reagents. A variety of substrates, reagents and chiral ligands were screened, resulting in improved catalytic methodology for allylic bromides in which enantioselectivities up to 88% were reached.     

Highly Regio‐ and Diastereoselective Palladium‐Catalyzed Allylic Substitution. Synthesis of 3‐(2‐Aminobutylidene)‐ 4‐arylazetidin‐2‐ones

The palladium‐catalyzed benzylamine attack to a particular allylic moiety, the 3‐alkenyl‐3‐bromoazetidin‐2‐one is herein reported. This reaction shows interesting mechanistic aspects and allows us to introduce in one step and under high regio‐ and stereocontrol the amino function in the C3 side chain of non‐conventional β‐lactams, thus offering the opportunity for designing new potential glutamine syntethase inhibitors, such as Tabtoxin analogues.     

Recent Advances in Palladium‐Catalyzed Cascade Cyclizations

The importance of palladium‐catalyzed cross coupling reactions in contemporary organic synthesis is undisputed and underlined by the Nobel Prize for Chemistry in 2010. In addition to the highly efficient cross coupling reactions for single C C bond construction, palladium‐catalyzed cascade processes involving multiple bond formations have emerged in recent years as valuable tools for the rapid synthesis of complex molecular scaffolds. This review presents an overview of the most relevant developments in this field, with a focus on the generation of diverse poly‐ and heterocyclic scaffolds. The generally well understood reactivity of palladium has allowed the discovery of many intriguing novel cascade processes, and the creativity of the synthetic community will undoubtedly lead to many more discoveries in the future.     

Palladium‐Catalyzed Intermolecular Allylic Dearomatization Reaction of α‐Substituted β‐Naphthol Derivatives: Scope and Mechanistic Investigation

A highly efficient dearomatization reaction of α‐substituted β‐naphthols with excellent chemoselectivity and regioselectivity has been developed. Mechanistic studies demonstrated that the dearomatized alkylation product is the thermodynamically more stable compound. The etherification product could be further transformed to the dearomatization product.

     

Remarkable Ligand Effects in Regioselective Palladium‐Catalysed Allylic Substitution Reactions

The use of tricyclohexylphosphine (and related phosphines) in palladium‐catalysed allylic substitution reactions enables the selective conversion of branched allylic acetates into the branched substitution products (up to 120:1 regioselectivity). Linear allylic acetates do not show the same selectivity for the branched substitution products, thereby demonstrating a memory effect.     

Palladium‐Catalyzed Heck‐Type Reactions of Allylic Esters with Arylboronic Acids or Potassium Aryltrifluoroborates

A selective and general route to (E)‐1,3‐diaryl‐prop‐1‐enes and (E)‐3‐arylallyl acetates has been developed by palladium‐catalyzed Heck‐type reactions of allylic esters with arylboronic acids or potassium aryltrifluoroborates. The present method selectively proceeds including β‐OAc elimination or β‐H elimination on the basis of the boronic acids. Whereas a variety of allylic esters were reacted with arylboronic acids, palladium(II) acetate [Pd(OAc)₂], tetra(n‐butyl)ammonium chloride [(n‐Bu)₄NCl] and postassium dihydrogen phosphate (KH₂PO₄) to afford the corresponding diarylation products in moderate to good yields, treatment of allylic esters with potassium aryltrifluoroborates furnished the corresponding monoarylation products.     

Highly Efficient Molybdenum(II)‐Catalyzed Intramolecular Allylic Alkylation of Arenes

The Friedel–Crafts‐type intramolecular allylic alkylation of simple arenes is performed in the presence of a catalytic amount of [Mo(II) (CO)₄Br₂]₂ (2.5 mol%). The moisture‐tolerant protocol provided a mild and direct access to a large library of functionalized 4‐vinyl‐1,2,3,4‐tetrahydronaphthalenes in high yields.     

A New Chiral P,N‐Ligand Derived from 1‐Phenylphospholane‐2‐carboxylic Acid (Phenyl‐P‐proline) for Palladium‐Catalyzed Asymmetric Allylic Substitution Reactions

New types of P,N‐ligands, cis‐ and trans‐ 3 , containing a tetrahydroisoquinoline skeleton as an N‐donor were synthesized from (1R,2S)‐1‐phenylphospholane‐2‐carboxylic acid (phenyl‐P‐proline, 1 ). The cis isomer, cis‐ 3 , was found to act as an excellent ligand in palladium‐catalyzed asymmetric allylic substitution reactions. The reactions of 1,3‐diphenyl‐2‐propenyl acetate ( 5 ) with several nucleophiles in the presence of [Pd(π‐allyl)Cl]₂, cis‐ 3 (Pd : ligand=1 : 2), and a base afforded the desired products in high yields with high enantioselectivity. It was suggested that these ligands did not serve as P,N‐bidentate ligands but as P‐monodentate ligands in these reactions.     

Iridium‐Catalyzed Asymmetric Allylic Amination with Polar Amines: Access to Building Blocks with Lead‐Like Molecular Properties

The combination of an air‐stable iridium catalyst and the dipolar aprotic solvent dimethyl sulfoxide (DMSO) allowed, for the first time, the systematic exploitation of highly polar, functionalized amines in asymmetric allylic substitutions: low molecular weight, sp³‐rich chiral building blocks were obtained with physicochemical properties that will be valuable in the synthesis of lead‐like small molecules.     

A Copper(II) Triflate‐Catalyzed Tandem Friedel–Crafts Alkylation/Cyclization Process towards Dihydroindenes

A one‐pot synthesis of dihydroindenes from substituted benzenes and haloalkenes was developed. The reaction proceeded via a copper(II) triflate [Cu(OTf)₂]‐catalyzed tandem Friedel–Crafts alkylation/cyclization process with high efficiency under relatively mild conditions.     

Palladium‐Catalyzed Intramolecular Coupling of Aryl Halides and Ketone Enolates: Synthesis of Hexahydro‐2,6‐methano‐1‐2

The palladium‐catalyzed intramolecular coupling of 2‐haloanilines and ketone enolates is a useful methodology for the synthesis of hexahydro‐2,6‐methano‐1‐2 derivatives. A study about the reaction conditions of the process is reported.     

Palladium‐Catalyzed Synthesis of Functional Tetralins via Benzylic Activation

2‐Monosubstituted, 2,2‐ and 2,3‐disubstituted tetralin derivatives have been synthesized from α,α′‐dihalo‐o‐xylenes and activated olefins using a palladium catalyst under basic conditions. The effects of temperature, base, palladium precursor and solvent have been fully explored, and this new catalytic reaction has been extended to a variety of substrates.     

Highly Enantioselective Zinc‐Catalyzed Friedel–Crafts Alkylation of Indoles with Ethyl Trifluoropyruvate

A highly enantioselective Friedel–Crafts alkylation of indoles with ethyl trifluoropyruvate has been developed using N,N′‐dioxide‐zinc(II) complexes. Both enantiomers of the desired adducts were obtained by the use of enantiomeric ligands in excellent results (up to 99% yield and 98% ee) within 0.5 h under mild conditions. On the basis of the experimental results, a proposed working model was proposed to explain the origin of the asymmetric induction.     

Pyranoside Phosphite‐Oxazoline Ligand Library: Highly Efficient Modular P,N Ligands for Palladium‐Catalyzed Allylic Substitution Reactions. A Study of the Key Palladium Allyl Intermediates

We have screened a library of modular phosphite‐oxazoline ligands for asymmetric allylic substitution reactions. The library is efficiently prepared from the commercially available and cheap D ‐glucosamine. The introduction of a phosphite moiety into the ligand design is highly advantageous for the product outcome. Therefore, this ligand library affords good‐to‐excellent reaction rates [TOFs up to 600 mol substrate×(mol Pd×h)⁻¹] and enantioselectivities (ees up to 99%) and, at the same time, shows a broad scope for mono‐, di‐ and trisubstituted linear hindered and unhindered substrates and cyclic substrates. The NMR studies on the palladium allyl intermediates provide a deeper understanding about the effect of the ligand parameters on the origin of enantioselectivity.