This paper describes the regioselective diamination of conjugated dienes using inexpensive Cu(I) as catalyst and N,N-di-tert-butylthiadiaziridine 1,1-dioxide as nitrogen source. The regioselectivity of diamination is likely due to dual mechanistic pathways which are greatly influenced by reaction conditions and the nature of the diene. A variety of useful internal and terminal cyclic sulfamides can be obtained in good yield.

Transamination of α-keto acids with transaminases and pyridoxamine phosphate is an important process to form optically active α-amino acids in biological systems. Various biomimetic transamination systems have been developed for carbonyl compounds including α-keto acid derivatives, fluoroalkyl ketones, and unactivated ketones with chiral vitamin B6 analogues, artificial transaminase mimics, chiral nitrogen sources, and chiral catalysts. This review provides a brief summary of this area.

An effective enantioselective 6-endo bromoaminocyclization of 2,4-dienyl N-tosylcarbamates catalyzed by a chiral phosphine oxide-Sc(OTf)3 complex is described. A wide variety of optically active 5-bromo-1,3-oxazinan-2-ones containing various functional groups can be obtained in 61–91% yields and 92–99% ees. An additive, such as NaCl, has been found to be crucial for the reaction process.

ConspectusVicinal diamines are important structural motifs present in various biologically and chemically significant molecules. Direct diamination of olefins provides an effective approach to this class of compounds. Unlike well-established oxidation processes such as epoxidation, dihydroxylation, and aminohydroxylation, direct diamination of olefins had remained a long-standing challenge and had been less well developed.In this Account, we summarize our recent studies on Pd(0)- and Cu(I)-catalyzed diaminations of olefins using di-tert-butyldiaziridinone and its related analogues as nitrogen sources via N–N bond activation. A wide variety of imidazolidinones, cyclic sulfamides, indolines, imidazolinones, and cyclic guanidines can be obtained from conjugated dienes and terminal olefins. For conjugated dienes, the diamination proceeds regioselectively at the internal double bond with the Pd(0) catalyst. Mechanistic studies show that the diamination likely involves a four-membered Pd(II) species resulting from the insertion of Pd(0) into the N–N bond of di-tert-butyldiaziridinone. Interestingly, the Cu(I)-catalyzed process occurs regioselectively at either the terminal or internal double bond depending on the reaction conditions via two mechanistically distinct pathways. The Cu(I) catalyst cleaves the N–N bond of di-tert-butyldiaziridinone to form a Cu(II) nitrogen radical and a four-membered Cu(III) species, which are likely in rapid equilibrium. The Cu(II) nitrogen radical and the four-membered Cu(III) species lead to the terminal and internal diamination, respectively.Terminal olefins are effectively C–H diaminated at the allylic and homoallylic carbons with Pd(0) as catalyst and di-tert-butyldiaziridinone as nitrogen source, likely involving a diene intermediate generated in situ from the terminal olefin via formation of a π-allyl Pd complex and subsequent β-hydride elimination. When di-tert-butylthiadiaziridine 1,1-dioxide is used as nitrogen source, cyclic sulfamides are installed at the terminal carbons via a dehydrogenative diamination process. When α-methylstyrenes (lacking homoallylic hydrogens) react with Pd(0) and di-tert-butyldiaziridinone, spirocyclic indolines are formed with generation of four C–N bonds and one spiro quaternary carbon via allylic and aromatic C–H amination.With Cu(I) catalysts, various terminal olefins can be effectively diaminated at the double bonds using di-tert-butyldiaziridinone, di-tert-butylthiadiaziridine 1,1-dioxide, and 1,2-di-tert-butyl-3-(cyanimino)-diaziridine as nitrogen sources, giving a variety of imidazolidinones, cyclic sulfamides, and cyclic guanidines in good yields, respectively. In the case of monosubstituted olefins using di-tert-butyldiaziridinone as nitrogen source, the resulting diamination products (imidazolidinones) are readily dehydrogenated under the reaction conditions, leading to the corresponding imidazolinones in good yields. Esters can also be diaminated to form the corresponding hydantoins with di-tert-butyldiaziridinone in the presence of a Cu(I) catalyst. A radical mechanism is likely to be operating in these Cu(I)-catalyzed reaction processes.Asymmetric processes have also been developed for the Pd(0)- and Cu(I)-catalyzed diamination reactions. Biologically active compounds such as (+)-CP-99,994 and Sch 425078 have been synthesized via the diamination processes. The diamination reactions described herein provide efficient methods to access a wide variety of vicinal diamines from readily available olefins and show great potential for synthetic applications.

An effective Pd(OAc)2-PPh3 catalyzed hydroesterification of alkenylphenols with phenyl formate as CO surrogate is described. A variety of lactones are obtained in generally high yields with high regioselectivities. In one case, 76% ee is obtained with a chiral ligand.

Transition-metal-catalyzed cross-coupling reactions are among the most powerful synthetic transformations. This paper describes an efficient copper-catalyzed homo- and cross-coupling of Grignard reagents with di-tert-butyldiaziridinone as oxidant under mild conditions, giving the coupling products in good to excellent yields. The reaction process has a broad substrate scope and is also effective for the C(sp)–C(sp3) coupling.

An effective Pd-catalyzed hydrocarboxylation of olefins with phenyl formate and formic acid is described. A variety of carboxylic acids are obtained in good yields with high regioselectivities under operationally simple conditions without the use of toxic CO gas.

An asymmetric intermolecular bromoesterification of unfunctionalized olefins catalyzed by (DHQD)2PHAL is described. Optically active bromoesters can be obtained with up to 92% ee.

This paper describes an efficient asymmetric biomimetic transamination of α-keto esters with a quinine-derived chiral base as the catalyst, giving a variety of β-branched α-amino esters in 50–96% yield and 87–95% ee.

This paper describes azidation of indoles with NaN3 and ceric ammonium nitrate (CAN), giving a variety of spirocyclic 2-azido indolines in good yields and moderate diastereoselectivities.

This paper describes a chiral base-catalyzed asymmetric biomimetic transamination of α-keto acetals. A wide variety of α-amino acetals containing various functional groups can be synthesized in 50–85% yield and 82–86% ee.

Optically active deuterated primary amines have been obtained with 78–98% ee’s from chiral N-tert-butanesulfinyl aldimines via reduction with N-Selectride and subsequent alcoholysis.

An effective enantioselective bromoaminocyclization of allyl N-tosylcarbamates catalyzed by a chiral phosphine–Sc(OTf)3 complex is described. A wide variety of optically active oxazolidinone derivatives containing various functional groups can be obtained with high enantioselectivities.

A novel and efficient Cu(I)-catalyzed oxidation of alcohols has been achieved with di-tert-butyldiaziridinone as the oxidant under mild conditions. A wide variety of primary and secondary alcohols with various functional groups can be oxidized to aldehydes and ketones in high yields. The reaction proceeds under neutral conditions making it compatible with acid- or base-sensitive substrates, and it is amenable to gram scale.

This paper describes the catalytic asymmetric diamination of alkyl dienes using N,N′-di-tert-butylthiadiaziridine 1,1-dioxide in the presence of Pd(0) and a chiral phosphoramidite ligand to give cyclic sulfamides in high yield and high ee. The diamination is also amenable to gram scale.

A mild and highly efficient Cu(I)-catalyzed oxidative coupling of anilines is described. Various primary and secondary anilines can be efficiently coupled under mild conditions to the corresponding azo compounds and hydrazines in high yields. This method provides a direct and practical access to these compounds and is also amenable to gram scale with no special precautions to exclude air or moisture.

An approach to the pentacyclic core of aspidophylline A is described. The strategy features CAN-mediated intramolecular azidoalkoxylation of enecarbamate and ruthenium-catalyzed atom transfer cyclization.

A novel Pd(0)-catalyzed sequential C–N bond formation process via allylic and aromatic C–H amination of α-methylstyrenes with di-tert-butyldiaziridinone, giving spirocyclic indolines in good yields, is described. Four C–N bonds and one spiro quaternary carbon are generated in a single operation.

This communication describes a chiral base-catalyzed asymmetric [1,3]-proton shift of trifluoromethyl ketimines, giving a wide variety of trifluoromethyl aldimines containing various functional groups with up to 94% ee.

Various novel palladium(II) complexes with tunable chiral and achiral anionic counterions have been prepared from dialkylpalladium(II) agents and characterized by NMR spectroscopy and X-ray diffraction.

A concise approach to the spiroiminal fragment of marineosins A and B is described. The key steps involve an acid-catalyzed N-acyliminium ion cyclization and a Vilsmeier–Haack type reaction with Tf2O.

An efficient cyclopropanation of olefins with Zn(CH2I)2, a catalytic amount of CCl3CO2H, and 1,2-dimethoxyethane at room temperature is described. A wide variety of olefins, including acid-sensitive substrates, can be cyclopropanated in 71–99% yield.

A novel and efficient Cu(I)-catalyzed oxidative homocoupling of terminal alkynes with diaziridinone as an oxidant is described. Various terminal alkynes can be transformed into the corresponding 1,3-diynes in good yields. The reaction process is base-free, operationally simple, and amenable to the gram scale.

This paper describes a chiral phosphoric acid-catalyzed sulfamination of amino-alkenes to form optically active 2-substituted pyrrolidines and piperidines in up to 86% ee.

Transition metal-catalyzed C–H amination at positions adjacent to double bonds and carbonyl groups is discussed in this critical review. While the focus will center on the recent developments of α-oxidative amination, some historical developments and mutually beneficial reports in the broader field of C–H amination will be discussed. C–H amination has become a viable method for the efficient installation of nitrogen atoms en route to target molecules (89 references).

An efficient asymmetric biomimetic transamination of α-keto esters with quinine derivatives as chiral bases was described. A wide variety of α-amino esters containing various functional groups can be synthesized in high yield and enantioselectivity.

An asymmetric biomimetic transamination of aromatic ketones to optically active amines with o-HOPhCH2NH2 as amine source catalyzed by hydroquinine-derived chiral base is described. Up to 85% ee was obtained.

An efficient stereoselective approach to the tetracyclic core of Cryptotrione, involving an asymmetric Michael addition, ring-closing metathesis, and subsequent cyclopropanation, is described.

The Simmons–Smith cyclopropanation is a widely used method to synthesize cyclopropanes from alkenes using methylene iodide and a zinc reagent. A novel class of organozinc species, RXZnCH2Y, has been found to efficiently cyclopropanate alkenes, including traditionally unreactive unfunctionalized alkenes. The reactivity and selectivity of this class of organozinc reagents can be regulated by tuning the electronic and/or steric nature of the RX group attached to Zn. During recent years, this class of organozinc reagent has been widely used in organic synthesis as a reagent for cyclopropanation and other useful synthetic transformations. Catalytic, asymmetric versions of this reaction have been developed providing high enantiomeric excess for unfunctionalized olefins.

The synthesis of optically pure (+)-ambrisentan has been achieved from 3,3-diphenylacrylate in four steps with 53% overall yield and >99% ee at the >100 g scale without column purification. The chiral epoxide intermediate was prepared via asymmetric epoxidation with a fructose-derived diacetate ketone as catalyst.

This paper describes an effective chiral base-catalyzed biomimetic transamination of α-keto esters using simple benzyl amines. A wide variety of α-amino esters containing various functional groups can be synthesized in high enantioselectivity and reasonable yield.

Conjugated dienes can be diaminated at the internal and/or terminal double bonds using Cu(I) as catalyst and N,N-di-t-butyldiaziridinone (1) as nitrogen source. The regioselectivity is highly dependent upon the choice of Cu(I) catalyst and the substituents on diene substrates. The diamination likely proceeds via two mechanistically distinct pathways. The N–N bond of N,N-di-t-butyldiaziridinone (1) is first homolytically cleaved by the Cu(I) catalyst to form four-membered Cu(III) species A and Cu(II) radical species B, which are in rapid equilibrium. The internal diamination likely proceeds in a concerted manner via Cu(III) species A, and the terminal diamination likely involves Cu(II) radical species B. Kinetic studies have shown that the diamination is first-order in N,N-di-t-butyldiaziridinone (1), zero-order in olefin, and first-order in total Cu(I) catalyst, and the cleavage of the N–N bond of 1 by the Cu(I) catalyst is the rate-determining step. The internal diamination is favored by use of CuBr without ligand and electron-rich dienes. The terminal diamination is favored when using CuCl–L and dienes with radical-stabilizing groups.

A mild acid-catalyzed formal allylic C−H oxidation of aryl cycloalkenes with N-propylthiosuccinimide in the presence of various nucleophiles to generate allylic ethers, esters, and sulfonamides is described. A possible reaction mechanism has been proposed.

An efficient acid-catalyzed sulfetherification of various unsaturated alcohols with sulfenamides to form tetrahydrofurans and tetrahydropyrans regioselectively is described. Mechanistic studies have shown that the tetrahydrofurans can stereoselectively rearrange to the corresponding tetrahydropyrans.

A novel Pd(II)-catalyzed aromatic C–H ethoxycarbonylation with oxaziridine involving C–C bond cleavage is described. Various aromatic 2-phenylpyridines and related compounds as well as aryl ureas can be effectively ethoxycarbonylated. A catalytic cycle involving Pd(II) and Pd(IV) is proposed.

A chiral phosphoric acid catalyzed enantioselective bromocyclization of olefins is described. Various cis-, trans-, or trisubstituted γ-hydroxy-alkenes and γ-amino-alkenes can cyclize under the reaction conditions to give optically active 2-substituted tetrahydrofurans and tetrahydropyrroles in up to 91% ee.

This paper describes the regioselective diamination of conjugated dienes using inexpensive Cu(I) as catalyst and N,N-di-tert-butylthiadiaziridine 1,1-dioxide as nitrogen source. The regioselectivity of diamination is likely due to dual mechanistic pathways which are greatly influenced by reaction conditions and the nature of the diene. A variety of useful internal and terminal cyclic sulfamides can be obtained in good yield.

This paper describes a FeCl3/NaI-catalyzed formal allylic C–H oxidation of arylalkenes using a catalytic amount of disulfide with BnOH and 4-nitroaniline as nucleophiles and air as oxidant to form the corresponding allyl ethers and amines. A possible reaction mechanism has been proposed.

Various dienes and a triene can be regioselectively diaminated at the internal double bond with good yields and high diastereoselectivity using di-tert-butyldiaziridinone (5) as the nitrogen source and Pd(PPh3)4 (1−10 mol %) as the catalyst. Kinetic studies with 1H NMR spectroscopy show that the diamination is first-order in total Pd catalyst and inverse first-order in PPh3. For reactive dienes, such as 1-methoxybutadiene (6g) and alkyl 1,3-butadienes (6a, 6j), the diamination is first-order in di-tert-butyldiaziridinone (5) and zero-order in the olefin. For olefins with relatively low reactivity, such as (E)-1-phenylbutadiene (6b) and (3E,5E)-1,3,5-decatriene (6i), similar diamination rates were observed when 3.5 equiv of olefins were used. Pd(PPh3)2 is likely to be the active species for the insertion of Pd(0) into the N−N bond of di-tert-butyldiaziridinone (5) to form a four-membered Pd(II) complex (A), which can be detected by NMR spectroscopy. The olefin complex (B), formed from intermediate A via ligand exchange between the olefin substrate and the PPh3, undergoes migratory insertion and reductive elimination to give the diamination product and regenerate the Pd(0) catalyst.

A dehydrogenation method using Cu(I) and either N,N-di-tert-butylthiadiaziridine 1,1-dioxide or N,N-di-tert-butyldiaziridinone is reported. The dehydrogenation allows a facile introduction of C–C double bond(s) into various carbocycles and heterocycles such as oxazolines and thiazolines.

This paper describes mechanistic studies on a dipeptide-promoted asymmetric cyclopropanation system for unfunctionalized olefins. Zinc species generated from the deprotonation of the N−H of the dipeptide ligand have been investigated by NMR and X-ray structure studies and are likely to be responsible for asymmetric cyclopropanation. ZnI2 plays an important role in promoting the reaction.

This paper describes a diamination process using di-tert-butyldiaziridinone as nitrogen source and CuCl as catalyst. A wide variety of disubstituted terminal olefins can be efficiently diaminated in good yields under mild condition. This diamination process was used to synthesize potent NK1 antagonist Sch 425078.

A variety of nonconjugated cis-olefins has been enantioselectively epoxidized with chiral ketones 2, and up to 92% ee has been obtained. The two prochiral faces of an olefin are likely stereodifferentiated by the relative hydrophobicity of the olefin substituents and/or allylic oxygen functionality.

A fructose-derived diacetate ketone has been shown to be an effective catalyst for asymmetric epoxidation. High ee values have been obtained for a variety of trans and trisubstituted olefins including electron-deficient α,β-unsaturated esters as well as certain cis olefins.

This paper describes an α-amination process of aryl ketones using CuCl as catalyst and di-tert-butyldiaziridinone as the nitrogen source. A variety of imidazolinone derivatives are prepared in moderate yields under mild conditions. A possible catalytic cycle is proposed for this reaction.

Asymmetric epoxidation of olefins by using an α,α-dimethylmorpholinone-containing chiral ketone catalyst (4) has been investigated. This ketone, which has the combined features of several previously studied catalysts, is an effective catalyst for trans- and trisubstituted olefins, and up to 97% ee has been achieved. The α,α-dimethyl group has significant impact on spiro and planar transition states.

The asymmetric epoxidation of various fluoroolefins has been studied using chiral ketone catalyst, and up to 93% ee was achieved with fructose-derived ketone 1.

Asymmetric epoxidation of various styrenes using carbocyclic oxazolidinone-containing ketone 3 has been investigated. High enantioselectivity (89–93% enantiomeric excess) has been attained for this challenging class of alkenes. Mechanistic studies show that substituents on the ketone catalyst can have electronic influences on secondary orbital interactions, which affects the competition between spiro and planar transition states and, ultimately, enantioselectivity. The results described herein not only reveal the potential of chiral dioxirane catalyzed asymmetric epoxidation as a viable entry into this important class of olefins but also further enhance the understanding of the mechanistic aspects of chiral ketone-catalyzed asymmetric epoxidation.

This paper describes the Cu(I)-catalyzed regioselective diamination of conjugated dienes using di-tert-butyldiaziridinone as nitrogen source. The internal diamination and terminal diamination likely proceed via two mechanistic pathways. Various dienes can be efficiently diaminated at the internal double bonds with high regio- and diasteroselectivity in good yield using inexpensive CuBr as catalyst.

An efficient cyclopropanation of olefins with Zn(CH2I)2, a catalytic amount of CCl3CO2H, and 1,2-dimethoxyethane at room temperature is described. A wide variety of olefins, including acid-sensitive substrates, can be cyclopropanated in 71–99% yield.

A concise approach to the spiroiminal fragment of marineosins A and B is described. The key steps involve an acid-catalyzed N-acyliminium ion cyclization and a Vilsmeier–Haack type reaction with Tf2O.

An effective enantioselective 6-endo bromoaminocyclization of 2,4-dienyl N-tosylcarbamates catalyzed by a chiral phosphine oxide-Sc(OTf)3 complex is described. A wide variety of optically active 5-bromo-1,3-oxazinan-2-ones containing various functional groups can be obtained in 61–91% yields and 92–99% ees. An additive, such as NaCl, has been found to be crucial for the reaction process.

An efficient stereoselective approach to the tetracyclic core of Cryptotrione, involving an asymmetric Michael addition, ring-closing metathesis, and subsequent cyclopropanation, is described.

Transamination of α-keto acids with transaminases and pyridoxamine phosphate is an important process to form optically active α-amino acids in biological systems. Various biomimetic transamination systems have been developed for carbonyl compounds including α-keto acid derivatives, fluoroalkyl ketones, and unactivated ketones with chiral vitamin B6 analogues, artificial transaminase mimics, chiral nitrogen sources, and chiral catalysts. This review provides a brief summary of this area.

Transition metal-catalyzed C–H amination at positions adjacent to double bonds and carbonyl groups is discussed in this critical review. While the focus will center on the recent developments of α-oxidative amination, some historical developments and mutually beneficial reports in the broader field of C–H amination will be discussed. C–H amination has become a viable method for the efficient installation of nitrogen atoms en route to target molecules (89 references).

Various novel palladium(II) complexes with tunable chiral and achiral anionic counterions have been prepared from dialkylpalladium(II) agents and characterized by NMR spectroscopy and X-ray diffraction.

This paper describes an efficient asymmetric biomimetic transamination of α-keto esters with a quinine-derived chiral base as the catalyst, giving a variety of β-branched α-amino esters in 50–96% yield and 87–95% ee.

An asymmetric biomimetic transamination of aromatic ketones to optically active amines with o-HOPhCH2NH2 as amine source catalyzed by hydroquinine-derived chiral base is described. Up to 85% ee was obtained.

This paper describes azidation of indoles with NaN3 and ceric ammonium nitrate (CAN), giving a variety of spirocyclic 2-azido indolines in good yields and moderate diastereoselectivities.

A novel and efficient Cu(I)-catalyzed oxidative homocoupling of terminal alkynes with diaziridinone as an oxidant is described. Various terminal alkynes can be transformed into the corresponding 1,3-diynes in good yields. The reaction process is base-free, operationally simple, and amenable to the gram scale.

The Simmons–Smith cyclopropanation is a widely used method to synthesize cyclopropanes from alkenes using methylene iodide and a zinc reagent. A novel class of organozinc species, RXZnCH2Y, has been found to efficiently cyclopropanate alkenes, including traditionally unreactive unfunctionalized alkenes. The reactivity and selectivity of this class of organozinc reagents can be regulated by tuning the electronic and/or steric nature of the RX group attached to Zn. During recent years, this class of organozinc reagent has been widely used in organic synthesis as a reagent for cyclopropanation and other useful synthetic transformations. Catalytic, asymmetric versions of this reaction have been developed providing high enantiomeric excess for unfunctionalized olefins.

This communication describes a chiral base-catalyzed asymmetric [1,3]-proton shift of trifluoromethyl ketimines, giving a wide variety of trifluoromethyl aldimines containing various functional groups with up to 94% ee.