NHC-Ni(II) Catalyzed Cyclopropene-Isocyanide [5+1] Benzannulation


Cyclopropenes are highly active building blocks in organic synthesis and frequently use for preparing cyclic compounds via [3+2], [2+3], [3+4] and other modes of cycloaddition.[1-4] The [5+1]-cycloaddition of cyclopropenes was rarely reported owning to the high homo-dimerization and polymerization reactivity of the cyclopropenes. Exceptional examples are those using CO as a reaction partner like the Dotz benzannulation and the Semmelhack/Wulff 1,4-hydroquinones synthesis.[5-7] The needs of stoichiometric amount of Cr/Mo/W(CO)n complexes and toxic CO gas have restricted the application of this method.

Fig. 1 [5+1] benzannulation of cyclopropene 1) Semmelhack/Wulff 1,4-hydroquinones synthesis from cyclopropene and CO. 2) (NHC)Ni(II) catalyzed cyclopropene-isocyanide [5+1] benzannulation.

As a continuation of our (NHC)Ni(II)-catalyzed strained cyclic olefin chemistry,[8, 9] we investigated the (NHC)Ni(II) potential in directing a cross-reaction between highly reactive cyclopropene and isocyanide.[10-12] Surprisingly, unlike the cyclopropene-alkyne cross-reaction that gave us a diene product, the reaction gave us a highly substituted naphthamine. The product structure is comparable with the Semmelhack/Wulff 1,4-hydroquinones synthesis by CO complexes. Subsequent optimization gave us a unique way to prepare functionalized arylamines or endocyclic dienes with high yield and good selectivity. The large steric hindrance of NHC (IPentAn) plays a key role to inhibit the cyclopropene homo-dimerization, the cyclopropene rearrangement to indene derivatives and isocyanide oligomerization.

Compared to traditional analogs, this synthetic method has several notable features: 1) it employs catalytic amount of Ni(II) as catalyst ; 2) it has broad substrates scopes and is compatible with many functional groups, including halide, ester, cyanide, heteroaryl and alkene; 3) it provides novel endocyclic 1,3-dienes bearing spiro-ring structures when ß,ß-disubsituted vinyl cyclopropenes are used; 4) it provides an access to diarylamines with a large steric hindrance, which are difficult to synthesis via traditional Buchwald-Hartwig couplings; and 5) it provides regioselective ring-opening when a cyclopropene bearing a trisubstituted olefin is used.

Fig. 2 Scope of (NHC)Ni(II) catalyzed cyclopropene-isocyanide [5+1] benzannulation

The heteroaromatic compounds and naphthamine products obtained from this method are potentially useful in medicinal, photochemical and material chemistry.[13, 14] For example, product 3rb bearing 2,3-dihydro-1H-phenalenes, which is a common motif in OLEDs. A solvent-controlled highly regioselective bromination on unsymmetric diaryl amine was also developed for higher functional product synthesis.

Fig. 3 Solvent-controlled regioselective bromination.

For more details, especially on substrate scope and mechanistic studies please see our article: https://www.nature.com/articles/s41467-022-31896-y


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