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Bicyclo[1.1.1]pentanes (BCPs) have found application as bioisosteres of aromatic rings in drug development. However, catalytic construction of this motif with adjacent stereocenters with high enantioselectivity from readily available starting materials still constitutes a significant synthetic challenge. Herein we report a direct stereoselective synthesis of α-chiral allylic BCPs by 1,3-difunctionalization of [1.1.1]propellane with Grignard reagents and allyl carbonates using iridium catalysis. This mild protocol proceeds via initial organometallic addition to [1.1.1]propellane followed by asymmetric allylic substitution, providing the products with high enantioselectivities over a broad range of substrates. Further derivatization of the products demonstrates the applicability of this method to the preparation of structurally diverse libraries of chiral BCP derivatives.

Chiral allene and N-heteroaryl motifs are present in an ever-growing list of biologically active natural products and synthetic drugs. Although significant progress has been made in asymmetric syntheses of chiral allenes, general and practical protocols for enantioselective syntheses of chiral N-heteroaryl-substituted allenes from readily available starting materials still remain rare. Here we report a highly enantioselective synthesis of quinolinyl-substituted chiral allenes through a copper-catalyzed asymmetric allenylation of quinoline N-oxides with readily available 1,3-enynes. A variety of 1,3-enynes react with quinoline N-oxides, affording the corresponding quinolinyl-substituted allenes in high yields (up to 95%) and high enantioselectivities (up to 99% ee). This transformation tolerates a variety of functional groups, such as chloro, bromo, trifluoromethyl ether, tertiary amine, siloxy, carboxylic ester, imide, pyridine, and thiophene moieties. DFT calculations suggest a pathway involving an intramolecular nucleophilic addition of an allenyl copper intermediate with a coordinated quinoline N-oxide through a five-membered, rather than seven-membered, transition state. Chiral allenes are useful chemical reagents, but efficient access to chiral heteroaryl allenes remains challenging. Here the authors report a copper-catalyzed asymmetric allenylation of quinoline N-oxides using 1,3-enynes, providing efficient access to axially chiral allenes bearing heteroarenes.

1,3-Disubstituted bicyclo[1.1.1]pentanes (BCPs) are valuable bioisosteres of para-substituted aromatic rings. The most direct route to these structures is via multicomponent ring-opening reactions of [1.1.1]propellane. However, challenges associated with these transformations mean that difunctionalized BCPs are more commonly prepared by multistep reaction sequences with BCP-halide intermediates. Herein, we report three- and four-component 1,3-difunctionalizations of [1.1.1]propellane with organometallic reagents, organoboronic esters, and a variety of electrophiles. This process is achieved by trapping intermediate BCP-metal species with boronic esters to form boronate complexes, which are versatile intermediates whose electrophile-induced 1,2-metallate rearrangement chemistry enables a broad range of C-C bond-forming reactions.

[1.1.1]Propellane is a highly strained tricyclic hydrocarbon whose reactivity is dominated by addition reactions across the central inverted bond to provide bicyclo[1.1.1]pentane derivatives. These reactions proceed under both radical and two-electron pathways, hence providing access to a diverse array of products. Conversely, transition metal-catalyzed reactions of [1.1.1]propellane are underdeveloped and lack synthetic utility, with reported examples generally yielding mixtures of ring-opened structural isomers, dimers, and trimers, often with poor selectivity. Herein, we report that nickel(0) catalysis enables the use of [1.1.1]propellane as a carbene precursor in cyclopropanations of a range of functionalized alkenes to give methylenespiro[2.3]hexane products. Computational studies provide support for initial formation of a Ni(0)-[1.1.1]propellane complex followed by concerted double C-C bond activation to give the key 3-methylenecyclobutylidene-nickel intermediate.

Rh-catalyzed redox-neutral coupling between N-aryl nitrones and alkynes has been achieved under relatively mild conditions. The reaction proceeded via C–H activation at the N-aryl ring with subsequent O-atom transfer, affording trisubstituted indolines in good chemoselectivity and moderate to good diasteroselectivity.

Rh(III)-catalyzed C-H activation of 2-phenylimidazo[1,2-a]pyridines in divergent oxidative coupling with alkynes has been achieved. Selective mono versus 2-fold C-H activation has been attained under condition control. When AgOAc was used as an oxidant, the coupling afforded 5,6-disubstituted naphtho[1',2':4,5]imidazo[1,2-a]pyridines as a result of initial nitrogen chelation-assisted C-H activation at the benzene ring followed by rollover C-H activation. In contrast, the reaction afforded a fused isoquinolinium salt as a result of C-C and C-N coupling when AgBF4 was employed as a co-oxidant. A rhodacyclic intermediate has been isolated.

The first transition metal-catalyzed stereoconvergent Markovnikov 1,2-hydrosilylation of (E/Z)-dienes was effectively achieved with excellent E-selectivities using a cobalt catalyst., We report the first stereoconvergent Markovnikov 1,2-hydrosilylation of conjugated dienes using catalysts generated from bench-stable Co(acac)2 and phosphine ligands. A wide range of E/Z-dienes underwent this Markovnikov 1,2-hydrosilylation in a stereoconvergent manner, affording (E)-allylsilanes in high isolated yields with high stereoselectivities (E/Z = >99 : 1) and high regioselectivities (b/l up to > 99 : 1). Mechanistic studies revealed that this stereoconvergence stems from a σ–π–σ isomerization of an allylcobalt species generated by the 1,4-hydrometalation of Z-dienes. In addition, a cobalt catalyst that can only catalyze the hydrosilylation of the E-isomer of an (E/Z)-diene was identified, which allows the separation of the (Z)-isomer from an isomeric mixture of (E/Z)-dienes. Furthermore, asymmetric hydrosilylation of (E)-1-aryl-1,3-dienes was studied with Co(acac)2/(R)-difluorphos and good enantioselectivities (er up to 90 : 10) were obtained.

Cp*Rh(III)-catalyzed intermolecular C-C couplings between activated α-diazocarbonyl compounds and arenes bearing a range of azacyclic directing groups have been achieved. This catalytic alkylation reaction operates under mild conditions with good functional group tolerance.

The rhodium(III)-catalyzed regioselective alkylation of (hetero)arenes using cyclopropanols as a reactive and efficient coupling partner under oxidative conditions has been developed. This coupling occurred at room temperature via C–H activation of arenes and C–C cleavage of cyclopropanols. Various types of (hetero)arenes (indolines, carbazole, tetrahydrocarbazole, pyrrole, thiophene, etc.) were all successfully reacted under the present conditions. This protocol provides the facile and efficient construction of C7-alkylated indoline scaffolds.

A series of Mn-complexes with tetradentate N 4 ligands, introducing aromatic groups into 2-pyridylmethyl positions of N,N′-dimethyl-N,N′-bis(2-pyridylmethyl)ethane-1,2-diamine ( mep ), N,N′-dimethyl-N,N′-bis(2-pyridylmethyl)cyclohexane- trans -diamine ( mcp ), have been synthesized and applied for epoxidation of olefins using H 2 O 2 as the oxidant. The Mn-complexes still possessed an octahedral mononuclear structure in a cis -α topology. These complexes showed good regioselectivity, high yields and turnover frequency (even up to 228,000 h −1 ) with low catalyst loading (0.1–0.01 mol%) for epoxidation of a family of olefins (including internal aromatic olefins, internal and terminal aliphatic olefins and diolefins).