Rhodium Enalcarbenoids: Direct Synthesis of Indoles by Rhodium(II)‐Catalyzed [4+2] Benzannulation of Pyrroles

Disclosed herein is the design of an unprecedented electrophilic rhodium enalcarbenoid which results from rhodium(II)‐catalyzed decomposition of a new class of enaldiazo compounds. The synthetic utility of these enalcarbenoids has been successfully demonstrated in the first transition‐metal‐catalyzed [4+2] benzannulation of pyrroles, thus leading to substituted indoles. The new benzannulation has been applied to the efficient synthesis of the natural product leiocarpone as well as a potent adipocyte fatty‐acid binding protein inhibitor.     

Dirhodium(II)‐Catalyzed Annulation of Enoldiazoacetamides with α‐Diazoketones: An Efficient and Highly Selective Approach to Fused and Bridged Ring Systems

A dirhodium(II)‐catalyzed annulation reaction between two structurally different diazocarbonyl compounds furnishes the donor–acceptor cyclopropane‐fused benzoxa[3.2.1]octane scaffold with excellent chemo‐, regio‐, and diastereoselectivity under exceptionally mild conditions. The composite transformation occurs by [3+2]‐cycloaddition between donor–acceptor cyclopropenes generated from enoldiazoacetamides and carbonyl ylides formed from intramolecular carbene–carbonyl cyclization in one pot with one catalyst. The annulation products can be readily transformed into benzoxa[3.3.1]nonane and hexahydronaphthofuran derivatives with exact stereocontrol. This method allows the efficient construction of three fused and bridged ring systems, all of which are important skeletons of numerous biologically active natural products.     

Dual Reactivity of 1,2,3,4‐Tetrazole: Manganese‐Catalyzed Click Reaction and Denitrogenative Annulation

A general catalytic method using a Mn‐porphyrin‐based catalytic system is reported that enables two different reactions (click reaction and denitrogenative annulation) and affords two different classes of nitrogen heterocycles, 1,5‐disubstituted 1,2,3‐triazoles (with a pyridyl motif) and 1,2,4‐triazolo‐pyridines. Mechanistic investigations suggest that although the click reaction likely proceeds through an ionic mechanism, which is different from the traditional click reaction, the denitrogenative annulation reaction likely proceeds via an electrophilic metallonitrene intermediate rather than a metalloradical intermediate. Collectively, this method is highly efficient and offers several advantages over other methods. For example, this method excludes a multi‐step synthesis of the N‐heterocyclic molecules described and produces only environmentally benign N₂ gas a by‐product.     

[CpRu]‐Catalyzed Carbene Insertions into Epoxides: 1,4‐Dioxene Synthesis through SN1‐Like Chemistry with Retention of Configuration

Rather than lead to the usual deoxygenation pathway, metal carbenes derived from α‐diazo‐β‐ketoesters undergo three‐atom insertions into epoxides using a combination of 1,10‐phenanthroline and [CpRu(CH₃CN)₃][BAr_F] as the catalyst. Original 1,4‐dioxene motifs are obtained as single regio‐ and stereoisomers. A perfect syn stereochemistry (retention, e.r. up to 97:3) is observed for the ring opening, which behaves as an S_N1‐like transformation.     

Silver(I)‐Catalyzed N‐Trifluoroethylation of Anilines and O‐Trifluoroethylation of Amides with 2,2,2‐Trifluorodiazoethane

A straightforward N‐trifluoroethylation of anilines has been developed based on silver‐catalyzed N? H insertions with 2,2,2‐trifluorodiazoethane (CF₃CHN₂). Mechanistically, the reaction is proposed to involve migratory insertion of a silver carbene as the key step. In contrast, when amides are employed as the substrates under similar reaction conditions, O‐trifluoroethylation occurs to afford trifluoroethyl imidates.     

Direct Synthesis of 5‐Aryl Barbituric Acids by Rhodium(II)‐Catalyzed Reactions of Arenes with Diazo Compounds

A commercially available rhodium(II) complex catalyzes the direct arylation of 5‐diazobarbituric acids with arenes, allowing straightforward access to 5‐aryl barbituric acids. Free N? H groups are tolerated on the barbituric acid, with no complications arising from N? H insertion processes. This method was applied to the concise synthesis of a potent matrix metalloproteinase (MMP) inhibitor.     

Enantioselective Synthesis of Spirocyclohexadienones by NHC‐Catalyzed Formal [3+3] Annulation Reaction of Enals

The enantioselective synthesis of pyrazolone‐fused spirocyclohexadienones was demonstrated by the reaction of α,β‐unsaturated aldehydes with α‐arylidene pyrazolinones under oxidative N‐heterocyclic carbene (NHC)catalysis. This atom‐economic and formal [3+3] annulation reaction proceeds through a vinylogous Michael addition/spiroannulation/dehydrogenation cascade to afford spirocyclic compounds with an all‐carbon quaternary stereocenter in moderate to good yields and excellent ee values. Key to the success of the reaction is the cooperative NHC‐catalyzed generation of chiral α,β‐unsaturated acyl azoliums from enals, and base‐mediated tandem generation of dienolate/enolate intermediates from pyrazolinones.     

Rhodium(II)‐Catalyzed Annulation of Azavinyl Carbenes Through Ring‐Expansion of 1,3,5‐Trioxane: Rapid Access to Nine‐Membered 1,3,5,7‐Trioxazonines

The rhodium(II)‐catalyzed denitrogenative coupling of N‐alkylsulfonyl 1,2,3‐triazoles with 1,3,5‐trioxane led to nine‐membered‐ringed trioxazonines in moderate‐to‐good yields. 1,3,5‐Trioxane, acting as an oxygen nucleophile, reacted with the α‐aza‐vinylcarbene intermediate, giving rise to ylide formation, which was probably the key step in the reaction. Triazoles that contained aryl substituents with various electronic and steric features on the C4 carbon atom were well‐tolerated. The synthesis of trioxazonine derivatives was achieved through a one‐pot, two‐step procedure from 1‐mesylazide and a terminal alkyne by combining Cu^I‐catalyzed 1,3‐dipolar cycloaddition and rhodium‐catalyzed transformations.     

An Efficient and Convenient Synthesis of Ethyl 1‐(4‐Methoxyphenyl)‐5‐phenyl‐1H‐1,2,3‐triazole‐4‐carboxylate

The “click chemistry” of using organic azides and terminal alkynes is arguably the most efficient and straightforward route to the synthesis of 1,2,3‐triazoles. In this paper, an alternative and direct access to ethyl 1‐(4‐methoxyphenyl)‐5‐phenyl‐1H‐1,2,3‐triazole‐4‐carboxylate is described. Treatment of ethyl diazoacetate with 4‐methoxyaniline derived aryl imines in the presence of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene provided fully substituted 1,2,3‐triazoles in good to high chemical yields. The base‐mediated reaction tolerates various substituted phenyl imines as well as ethyl diazoacetate or the more bulky diazoacetamide. A reasonable mechanism is proposed that involves the addition of an imine nitrogen atom to the terminal nitrogen atom of the diazo compound, followed by aromatization to give the 1,2,3‐triazole. The presence of the 4‐carboxy group is advantageous as it can be easily transformed into other functional groups.     

Formal Synthesis of (±)‐Trachelanthamidine via Base‐Induced Formal [3+2] Annulation and Intramolecular Cyclization

Base‐induced coupling/cyclization stepwise [3+2] annulation of α‐sulfonylacetamide with (Z)‐2‐bromoacrylates yielded polysubstituted pyroglutamates with three contiguous chiral centers with trans‐trans orientation in a one‐pot synthesis. The pyrrolizidine skeleton was obtained via an intramolecular cyclization. This facile strategy was used to synthesize (±)‐trachelanthamidine.     

Rh(III)‐Catalyzed Denitrogenative [4+2] Annulation of Benzamides and 3‐Diazoindolin‐2‐imines: Expedient Access to Indolo[2,3‐c] isoquinolin‐5‐ones

An effective and pragmatic strategy for the synthesis of structurally diverse indolo[2,3‐c]isoquinolin‐5‐ones has been developed via a Rh(III)‐catalyzed C?H activation and [4+2] annulation reaction of N‐methoxybenzamides and 3‐diazoindolin‐2‐imines. The reaction involves the efficient formation of two new (one C?C and one C?N) bonds under operationally simple conditions and has the benefits of a broad substrate scope.     

A Novel Pd‐Catalysed Annulation Reaction for the Syntheses of Pyrroloindoles and Pyrroloquinolines

Pd‐catalysed annulation reactions between indole derivatives and internal alkyne esters leading to various pyrrolo[1,2‐a]indoles and pyrroloquinolines have been developed. The strategy involves an intermolecular addition of the indole nitrogen on to the internal alkyne ester followed by an intramolecular insertion of a vinyl–palladium complex into the carbonyl group. This method offers a facile and practical approach to pyrrolo[1,2‐a]indoles and pyrroloquinolines.     

Enantioselective Denitrogenative Annulation of 1H‐Tetrazoles with Styrenes Catalyzed by Rhodium

Sulfonylation of 1H‐tetrazoles with triflic anhydride in the presence of chiral rhodium(II) carboxylate dimers causes denitrogenation to generate α‐azo rhodium(II) carbenoid species as new types of donor/acceptor carbenoids, which then readily react with styrenes to afford 3,5‐diaryl‐2‐pyrazolines with a high degree of enantioselectivity.     

Stereoselective Synthesis of Functionalized Pyrrolidines by the Diverted N−H Insertion Reaction of Metallocarbenes with β‐Aminoketone Derivatives

A highly stereoselective route to functionalized pyrrolidines by the metal‐catalyzed diverted N?H insertion of a range of diazocarbonyl compounds with β‐aminoketone derivatives is described. A number of catalysts (rhodium(II) carboxylate dimers, copper(I) triflate, and an iron(III) porphyrin) are shown to promote the process under mild conditions to give a wide range of highly substituted proline derivatives. The reaction starts as a metallocarbene N?H insertion but is diverted by an intermolecular aldol reaction.