Haifeng Du

Catalytic Asymmetric Allylic and Homoallylic Diamination of Terminal Olefins via Formal C−H Activation

This paper describes a catalytic asymmetric diamination process for terminal olefins at allylic and homoallylic carbons via formal C-H activation using di-tert-butyldiaziridinone as nitrogen source with a catalyst generated from Pd2(dba)3 and chiral phosphorus amidite ligand. A wide variety of readily available terminal olefins can be effectively diaminated in good yields with high regio-, diastereo-, and enantioselectivities.

Synthetic and mechanistic studies on Pd(0)-catalyzed diamination of conjugated dienes.

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(PPh(3))(4) (1-10 mol %) as the catalyst. Kinetic studies with (1)H NMR spectroscopy show that the diamination is first-order in total Pd catalyst and inverse first-order in PPh(3). 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(PPh(3))(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 PPh(3), undergoes migratory insertion and reductive elimination to give the diamination product and regenerate the Pd(0) catalyst.

Catalytic Diamination of Olefins via N–N Bond Activation

Conspectus Vicinal 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.

Cu(I)-Catalyzed Diamination of Conjugated Olefins with Tunable Anionic Counterions. A Possible Approach to Asymmetric Diamination

Various achiral and chiral Cu(I) salts have been prepared from mesitylcopper(I) and investigated for the diamination of conjugated olefins with 1,3-di-tert-butyldiaziridinone as nitrogen source. It has been found that copper(I) phosphate has high catalytic activity for the diamination, and encouraging ees have also been achieved with chiral phosphates as anionic counterions.

Cu(I)-catalyzed asymmetric diamination of conjugated dienes.

A Cu(I)-catalyzed asymmetric diamination for a variety of conjugated dienes and a triene with encouraging ees has been effectively achieved using (R)-DTBM-SEGPHOS as a chiral ligand and di- tert-butyldiaziridinone as the nitrogen source.

Cu(I)-Catalyzed Cycloguanidination of Olefins

This paper describes a novel cycloguanidination process using CuCl as catalyst and diaziridinimines as the nitrogen source. A variety of conjugated dienes, trienes, and terminal olefins can be effectively diaminated under mild reaction conditions. For dienes and trienes, the reaction occurs at the terminal double bond with high regioselectivity.

A Cu(I)-Catalyzed C−H α-Amination of Esters. Direct Synthesis of Hydantoins

This paper describes a novel intermolecular alpha-amination process of esters using CuCl as catalyst and di-tert-butyldiaziridinone as nitrogen source. A variety of hydantoins can be formed effectively under mild reaction conditions.

Mechanistic studies on a dipeptide-promoted asymmetric cyclopropanation of unfunctionalized olefins.

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. ZnI(2) plays an important role in promoting the reaction.

Cu(I)-Catalyzed C−H α-Amination of Aryl Ketones: Direct Synthesis of Imidazolinones

This paper describes an alpha-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.