Enantioselective Synthesis of Pyrrole‐Based Spiro‐ and Polycyclic Derivatives by Iridium‐Catalyzed Asymmetric Allylic Dearomatization and Controllable Migration Reactions

The first highly diastereo‐ and enantioselective synthesis of five‐membered spiro‐2H‐pyrroles was achieved using an Ir‐catalyzed asymmetric allylic dearomatization reaction. The spiro‐2H‐pyrrole derivatives readily undergo a controllable and stereospecific allylic migration under acid catalysis, providing polycyclic pyrrole derivatives in excellent yields and ee values. Additionally, the novel Ir‐complex K1 , derived from [Ir(cod)Cl]₂ (cod=1,5‐cyclooctadiene) and N‐benzhydryl‐N‐phenyldinaphthophosphoramidite (BHPphos), showed excellent control of both diastereo‐ and enantioselectivities.     

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

Reported herein is a copper‐catalyzed S_N2′‐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 S_N2′‐selective allylic substitution reaction to produce branched alkylboronates. The synthetic utilities of the obtained alkylboronates are also presented.     

Copper‐Catalyzed Enantioselective Allyl–Allyl Coupling between Allylic Boronates and Phosphates with a Phenol/N‐Heterocyclic Carbene Chiral Ligand

Copper‐catalyzed enantioselective allyl–allyl coupling between allylboronates and either Z‐acyclic or cyclic allylic phosphates using a new chiral N‐heterocyclic carbene ligand, bearing a phenolic hydroxy, is reported. This reaction occurs with exceptional S_N2′‐type regioselectivities and high enantioselectivities to deliver chiral 1,5‐diene derivatives with a tertiary stereogenic center at the allylic/homoallylic position.     

Transformations of Modified Morita‐Baylis‐Hillman Adducts from Isatins Catalyzed by Lewis Bases

The development of synthetic protocols to access architectures with broad structural and functional diversity from readily available starting materials is very attractive in both organic and medicinal chemistry fields. Toward this objective, the multifunctional isatin‐derived Morita‐Baylis‐Hillman (MBH) adducts provide opportunities to construct a variety of complex scaffolds containing a “privileged” oxindole motif through several catalytic pathways. By forming the ammonium or phosphonium salts with Lewis bases, isatin‐derived MBH adducts can undergo allylic substitutions with a range of nucleophiles, usually in a S_N2′‐S_N2′ pattern. Besides, assisted by Brønsted bases, the corresponding onium salts can be converted into the allylic ylide intermediates, which can undergo various annulation reactions or even 1,3‐difunctionalizations. Moreover, recent cooperative catalysis of Lewis bases and transition metal complexes further puts forward the application of isatin‐derived MBH adducts. This tutorial review covers the significant transformations of isatin‐derived MBH adducts, mostly in an asymmetric version, catalyzed by various Lewis bases over the past decade.     

Anilines as C‐Nucleophiles in Ir‐Catalyzed Intramolecular Asymmetric Allylic Substitution Reactions

Anilines generally act as N‐nucleophiles in transition‐metal‐catalyzed allylic substitution reactions. In this paper, a highly enantioselective intramolecular Friedel–Crafts‐type allylic alkylation of aniline derivatives was realized by using an iridium catalyst derived from [Ir(cod)Cl]₂ and (R _a)‐BHPphos. Various tetrahydroisoquinilin‐5‐amines were obtained in moderate to good yields, excellent enantioselectivity and regioselectivity under mild reaction conditions. BHPphos=N ‐benzhydryl‐N ‐phenyldinaphthophosphoramidite.     

Asymmetric Synthesis of Allylic Sulfonic Acids: Enantio‐ and Regioselective Iridium‐Catalyzed Allylations of Na2SO3

An enantioselective allylation reaction of allylic carbonates with sodium sulfite (Na₂SO₃) catalyzed by Ir complex was accomplished, providing allylic sulfonic acids in good to excellent yields with a high level of enantio‐ and regioselectivities. (R)‐2‐Phenyl‐2‐sulfoacetic acid, a key intermediate for the synthesis of Cefsulodin and Sulbenicillin, was synthesized as well.     

Ligand‐Controlled Regiodivergent and Enantioselective Copper‐Catalyzed Hydroallylation of Alkynes

A ligand‐controlled regiodivergent and enantioselective copper‐catalyzed intermolecular hydroallylation of alkynes with allylic phosphates and hydrosilanes has been achieved for the first time. The chiral bidentate sulfonate‐containing N‐heterocyclic carbene ligated CuCl complex leads to enantioenriched S_N2′‐type products, whereas the use of the IMesCuCl catalyst affords S_N2‐type products. Thus a range of chiral branched and achiral linear 1,4‐dienes could be facilely synthesized from readily available alkynes in a regiodivergent manner.     

Using N‐Tosylhydrazone as a Double Nucleophile in the Palladium‐Catalyzed Cross‐Coupling Reaction To Synthesize Allylic Sulfones

Without extra addition of sulfinate salt, allylic sulfones were synthesized by palladium‐catalyzed cross‐coupling of aryl iodide with N‐tosylhydrazone. In this transformation, not only the diazo compound but also the sulfinate salt, which were both generated in situ from base‐mediated decomposition of the N‐tosylhydrazone, was used as nucleophilic partner.     

Copper‐Catalyzed Ritter‐Type Reaction of Unactivated Alkenes with Dichloramine‐T

It was shown that dichloramine‐T ( 1 ) reacted with cyclohexene in acetonitrile to give N¹‐(2‐chlorocyclohexyl) amidine 2a and N‐(2‐chlorocyclohexyl)acetamide ( 3 ) via the competitive addition of acetonitrile and N‐chloro‐N‐tosylamino anion to cyclohexenechloronium ion. This reaction can be catalyzed by Cu(OAc)₂, primarily affording 2a . Furthermore, the resulting 2a can be cyclized to benzimidazol 14a in good yield by treating with KOH in dioxane.     

Latent Nucleophiles in Lewis Base Catalyzed Enantioselective N‐Allylations of N‐Heterocycles

Latent nucleophiles are compounds that are themselves not nucleophilic but can produce a strong nucleophile when activated. Such nucleophiles can expand the scope of Lewis base catalyzed reactions. As a proof of concept, we report that N‐silyl pyrroles, indoles, and carbazoles serve as latent N‐centered nucleophiles in substitution reactions of allylic fluorides catalyzed by Lewis bases. The reactions feature broad scopes for both reaction partners, excellent regioselectivities, and produce enantioenriched N‐allyl pyrroles, indoles, and carbazoles when chiral cinchona alkaloid catalysts are used.     

Palladium‐Catalyzed Asymmetric Allylic Alkylations with Toluene Derivatives as Pronucleophiles

The first two highly enantioselective palladium‐catalyzed allylic alkylations with benzylic nucleophiles, activated with Cr(CO)₃, have been developed. These methods enable the enantioselective synthesis of α‐2‐propenyl benzyl motifs, which are important scaffolds in natural products and pharmaceuticals. A variety of cyclic and acyclic allylic carbonates are competent electrophilic partners furnishing the products in excellent enantioselectivity (up to 99 % ee and 92 % yield). This approach was employed to prepare a nonsteroidal anti‐inflammatory drug analogue.     

Palladium‐Catalyzed Direct C2 Arylation of N‐Substituted Indoles with 1‐Aryltriazenes

A novel and efficient palladium‐catalyzed C2 arylation of N‐substituted indoles with 1‐aryltriazenes for the synthesis of 2‐arylindoles was developed. In the presence of BF₃ ? OEt₂ and palladium(II) acetate (Pd(OAc)₂), N‐substituted indoles reacted with 1‐aryltriazenes in N,N‐dimethylacetamide (DMAC) to afford the corresponding aryl–indole‐type products in good to excellent yields.     

Ligand‐Controlled Copper‐Catalyzed Highly Regioselective Difluoromethylation of Allylic Chlorides/Bromides and Propargyl Bromides

Highly regiodivergent copper‐catalyzed allylic/propargylic difluoromethylation reactions by employing different ligands are described. When 5,6‐dimethyl‐1,10‐phenanthroline was used as the ligand, exclusively α‐difluoromethylated products were obtained, while γ‐selective difluoromethylated products were generated when N‐heterocyclic carbene‐SIPr was used as the ligand. Likewise, high α‐ vs. γ‐selectivities were achieved in the presence of similar copper catalysts for the reactions of propargyl bromides. Moreover, a copper‐catalyzed asymmetric allylic difluoromethylation reaction with moderate to good enantioselectivity by the use of chiral ligands was developed.     

Pentacoordinated Carboxylate π‐Allyl Nickel Complexes as Key Intermediates for the Ni‐Catalyzed Direct Amination of Allylic Alcohols

Direct amination of allylic alcohols with primary and secondary amines catalyzed by a system made of [Ni(1,5‐cyclooctadiene)₂] and 1,1′‐bis(diphenylphosphino)ferrocene was effectively enhanced by adding nBu₄NOAc and molecular sieves, affording the corresponding allyl amines in high yield with high monoallylation selectivity for primary amines and high regioselectivity for monosubstituted allylic alcohols. Such remarkable additive effects of nBu₄NOAc were elucidated by isolating and characterizing some nickel complexes, manifesting the key role of a charge neutral pentacoordinated η³‐allyl acetate complex in the present system, in contrast to usual cationic tetracoordinated complexes earlier reported in allylic substitution reactions.     

Cobalt‐Catalyzed Regio‐ and Stereoselective Hydroboration of Allenes

An efficient pincer‐ligand‐based cobalt‐complex‐catalyzed allene hydroboration affording Z‐allylic boronates is described. The reaction demonstrates an excellent regio‐ as well as Z‐stereoselectivity and a wide substrate scope that tolerates many functional groups. Based on solvent‐assisted electrospray ionization mass spectrometry (SAESI‐MS) studies, a rationale for the cobalt‐catalyzed hydroboration involving the highly selective insertion of an allene into the Co?H bond to form Z‐allylic cobalt intermediates is proposed.     

Synthesis of Heterocycles through Transition‐Metal‐Catalyzed Isomerization Reactions

Metal‐catalyzed isomerization of N‐ and O‐allylic systems is emerging as an effective method to form synthetically useful iminium and oxocarbenium intermediates. In the presence of tethered nucleophiles, several recent examples illuminate this approach as a powerful strategy for the synthesis of structurally complex and diverse heterocycles. In this Concept article, we attempt to cover this area of research through a selection of recent versatile examples.     

Ruthenium‐Catalyzed Tandem‐Isomerization/Asymmetric Transfer Hydrogenation of Allylic Alcohols

A one‐pot procedure for the direct conversion of racemic allylic alcohols to enantiomerically enriched saturated alcohols is presented. The tandem‐isomerization/asymmetric transfer hydrogenation process is efficiently catalyzed by [{Ru(p‐cymene)Cl₂}₂] in combination with the α‐amino acid hydroxyamide ligand 1 , and performed under mild conditions in a mixture of ethanol and THF. The saturated alcohol products are isolated in good to excellent chemical yields and in enantiomeric excess up to 93 %.     

PEG‐4000‐promoted palladium‐catalyzed N‐allylation in water: aminonaphthalene as an example

An environmentally friendly, efficient catalytic process using palladium associated with ligands in a PEG4000–water system leading to N‐allylation was described in this study. PEG‐4000 was found to improve the palladium‐catalyzed allylic amination of allylic acetates with aminonaphthalenes and gave overall good to high yields of the corresponding N‐allylic aminonaphthalenes. Copyright © 2012 John Wiley & Sons, Ltd.     

Disulfonimide‐Catalyzed Asymmetric Reduction of N‐Alkyl Imines

A chiral disulfonimide (DSI)‐catalyzed asymmetric reduction of N‐alkyl imines with Hantzsch esters as a hydrogen source in the presence of Boc₂O has been developed. The reaction delivers Boc‐protected N‐alkyl amines with excellent yields and enantioselectivity. The method tolerates a large variety of alkyl amines, thus illustrating potential for a general reductive cross‐coupling of ketones with diverse amines, and it was applied in the synthesis of the pharmaceuticals (S)‐Rivastigmine, NPS R‐568 Hydrochloride, and (R)‐Fendiline.     

Enantioselective Allylic Alkylation Catalyzed by Novel C2‐Symmetric Bisphosphinites

In this article, we present our results concerning new C₂‐symmetric bisphosphinites with a (1R,2R)‐1,2‐bis([1,1′: 3′,1″‐terphenyl]‐5′‐yl)ethane backbone. For the given chirality of the backbone, derivatives with aromatic and aliphatic substituents at the donor P‐atoms were synthesized with moderate yields in a straightforward manner. These compounds were evaluated in the Pd⁰‐catalyzed enantioselective allylic alkylations (up to 67% ee).