Cu(I)-Catalyzed Regioselective Diamination of Conjugated Dienes via Dual Mechanistic Pathways

Abstract

Diamination of olefins presents an effective strategy to access vicinal diamine moieties which are contained in various biologically active molecules and are widely used as chiral control elements in asymmetric synthesis.1 Various metal-mediated and metal-catalyzed diamination processes have been reported.1-8 In our earlier studies, we have shown that conjugated dienes can be regioselectively diaminated using Pd(0)9 and Cu(I)10 as catalysts and di-tert-butyldiaziridinone (2)11 , 12 as nitrogen source. The Pd(0)-catalyzed diamination occurred regioselectively at the internal double bonds of dienes,9 and the Cu(I)-catalyzed diamination occurred primarily at the terminal double bonds with 10 mol% CuCl-P(OPh) 3 (Scheme 1).10 The Cu(I)-catalyzed diamination was proposed to proceed via a stepwise radical mechanism involving a Cu(II) species. During our ongoing studies, it was a surprise to find that the Cu(I)-catalyzed diamination could occur regioselectively at the internal double bond under certain conditions (e.g. with CuBr as catalyst) (Scheme 1). The reaction is likely to proceed via a concerted mechanism involving a four-membered Cu(III) species. Herein, we wish to report our preliminary studies on this subject.

Methods for direct alkene diamination, new & old

“…268 Using di- tert -butyldiaziridinone ( 402 ) as the nitrogen source, a diverse range of substrates, including 1-substituted, 1,2-disubstitiuted, 1,3-disubstituted, cyclic and even 1,2,3-trisubstituted dienes undergo reaction to form imidazolidinones 421 in high yield and regioselectivity. Notably, diamination under these conditions can also be conducted on large scale; e.g.…”

Complementary Regioselectivity in the Cu(I)-Catalyzed Diamination of Conjugated Dienes To Form Cyclic Sulfamides

“…Very recently, we found that the regioselectivity of diamination of conjugated dienes can be highly influenced by reaction conditions, choice of Cu(I) catalyst, and substrates used (Scheme 1). 12 It is proposed that the regioselectivity of this diamination is a result of dual mechanistic pathways. Complementary to the previously reported conditions using CuCl-P(OPh) 3 10a yielding terminal diamination, it was shown that with 5-10 mol % CuBr as catalyst, the internal double bond of conjugated dienes could be efficiently diaminated with very high selectivity 12.…”

“…12 It is proposed that the regioselectivity of this diamination is a result of dual mechanistic pathways. Complementary to the previously reported conditions using CuCl-P(OPh) 3 10a yielding terminal diamination, it was shown that with 5-10 mol % CuBr as catalyst, the internal double bond of conjugated dienes could be efficiently diaminated with very high selectivity 12. While the terminal diamination products are consistent with a step-wise radical process, the internal diamination products are consistent with a mechanism similar to that of the proposed, concerted Pd(0)-catalyzed diamination of conjugated dienes 9a.…”

“…Although further mechanistic studies are needed, it is proposed that the mechanism of diamination proceeds via dual mechanistic pathways analogous to that of the Cu(I)-catalyzed diamination using 1 as nitrogen source 12. As shown in Scheme 4, insertion of the Cu(I) catalyst into the N-N bond of 2 results in the formation of Cu(III) species 10 in equilibrium with Cu(II) radical species 9 .…”

Acyclic and Cyclic Ureas (Update 2013)

“…The regioselectivity of the reaction can be controlled by the choice of the catalyst: in the presence of 10 mol% copper(I) chloride/triphenylphosphite or copper(I) chloride/tricyclohexylphosphine, diamination occurs at the terminal double bond of conjugated dienes to give mainly imidazolidin-2-ones 35, [156] whereas 5 mol% copper(I) bromide directs product formation to involve the internal double bond similar to the palladium(0)-catalyzed diamination, and results mainly in imidazolidin-2-ones 36 as a mixture of enantiomers (Scheme 54). [157] The addition of chiral ligands also allows the copper-catalyzed version of this 1,2-diamination reaction to proceed in an enantioselective fashion. [158] Scheme 54 Copper-Catalyzed 1,2-Diamination Employing 1,2-Di-tert-butyldiaziridin-3one [ [157] Importantly, this reaction is not restricted to dienes or trienes as the substrates.…”