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The geminal difluorocyclobutane core is a valuable structural element in medicinal chemistry. Strategies for gem-difluorocyclobutanes, especially the 2-substituted cases, are limiting and often suffer from harsh reaction conditions. Reported herein is a m

Aluminum(I) and magnesium(I) compounds are reported for the C-C σ-bond activation of strained alkylidene cyclopropanes. These reactions result in the formal addition of the C-C σ bond to the main group center either at a single site (Al) or across a metal-metal bond (Mg-Mg). Mechanistic studies suggest that rather than occurring by a concerted oxidative addition, these reactions involve stepwise processes in which substrate binding to the main group metal acts as a precursor to α- or β-alkyl migration steps that break the C-C σ bond. This mechanistic understanding is used to develop the magnesium-catalyzed hydrosilylation of the C-C σ bonds of alkylidene cyclopropanes.

Methylenecyclopropanes (MCP) undergo ring opening reactions with group I and II metal halides and ammonium halides in liquid SO2 to afford homoallylic halides, which are versatile reagents in organic synthesis. The developed reaction conditions are compatible with acid-labile substrates such as N-Boc-protected compounds. Liquid SO2 is a polar reaction medium with Lewis acid properties that solubilizes inorganic salts. The unique properties of SO2 were demonstrated by control experiments: 1) upon performing the reactions with the aforementioned salts in conventional solvents, the MCP ring opening was not observed either in the presence of catalytic amounts of H3PO4 (similar pKa to that of H2SO3), or in the absence of H3PO4; 2) a solution of SO2 in THF exhibited similar properties to that of liquid SO2.

The hydroperoxidation of alkylidenecyclopropanes and other strained alkenes using an N-hydroxylamine and molecular oxygen occurred in the absence of catalyst, initiator, or light. The oxidation reaction proceeds through a radical pathway that is initiated by autoxidation of the alkene substrate. The hydroperoxides were converted to their corresponding alcohols and ketones under mild conditions.

We herein report a general organocatalytic enantioselective strategy for the construction of highly strained spiro[2,3]hexane skeletons from methylenecyclopropanes and a broad selection of α,β-unsaturated aldehydes. The reaction proceeds through a Michael addition followed by ring expansion of methylenecyclopropanes and nucleophilic attack of an enamine to realize the construction of spiro[2,3]hexanes. Key to the success of this approach are the utilization of an electron-deficient difluoro-substituted secondary amine catalyst and the intrinsic reactivity of methylenecyclopropanes.

The first intermolecular ring-opening hydroacylation of alkylidenecyclopropanes with chelating aldehydes through a rhodium-catalyzed acrylamide-promoted protocol is reported. This highly efficient catalytic system enables the direct synthesis of a diverse

A synthetic strategy with the visible-light photo-catalytic synergistic combination of electron and energy transfer processes has been developed. The mild reaction conditions allow the radical-radical cross-coupling phenomenon for the multicomponent synthesis of β-arylsulfonyl(diarylphosphinoyl)-α,α-diarylethyl-amines from readily available arylsulfinic acids (diarylphosphine oxides), 1,1-diarylethylenes and arylazides.

Without using any transitionmetal and base, an eco-friendly, practical and economical protocol has been established for the one-pot synthesis of diverse (E)-1-phenyl-4-sulfonylbut-1-enes from easily accessible starting materials. This strategy features a wide substrate scope, tolerates a broad range of functional groups, employs a less expensive oxidant, is operationally simple, and can be easily scaled-up. (Figure presented.).

A novel visible-light-catalyzed sulfonylation/arylation of carbon-carbon σ-bond with sulfonyl chlorides for the synthesis of 3-sulfonylated 1,2-dihydronaphthalenes is developed. This difunctionalization proceeds via a sequence of C=C bond sulfonylation, C-C σ-bond cleavage, and intramolecular cyclization, and the experiment result shows that the C-C σ-bond difunctionalization reaction includes a radical process. This strategy provides a simple and convenient route for difunctionalization of C-C bonds with an aromatic carbon and a sulfonyl radical by one-pot construction of a C-S bond and a new C-C bond.

A nickel-catalyzed hydrocyanation triggered by hydronickelation of the carbon-carbon double bonds of allenes followed by cyclopropane cleavage is described. The observed regio- and stereochemistries in the products are strongly influenced by the initial hydronickelation step, and allenyl- and methylenecyclopropanes reacted smoothly to promote the cleavage of cyclopropane. In contrast, this cleavage was not observed with vinylidenecyclopropanes, because the initial hydronickelation does not give a suitable intermediate for cleavage of the cyclopropanes. (Figure presented.).

A novel visible-light-induced aza-pinacol rearrangement was developed for the first time. In this approach, the addition of the N-centered radical to the C=C bond of alkylidenecyclopropanes delivers a variety of cyclobutanimines and γ-butyrolactones, with

Substituted alkylidenecyclopropanes reacted with 5 equivalents each of Me3Al and CH2I2 at room temperature in hexane to give 1-mono- and 1,1-disubstituted spiro[2.2]pentanes in high yields. Surprisingly, the same reaction

Catalyst screening and optimization of reaction conditions allowed control of the organoselenium-catalyzed oxidative ring expansion of highly active methylenecyclopropanes to give substituted cyclobutanones selectively. This protocol employs H2O2 as a clean oxidant and generates no waste and, therefore, provides green access to useful, but not readily available, substituted cyclobutanones under mild conditions.

Copper(I)-catalyzed intramolecular trifluoromethylation of methylenecyclopropanes has been developed to produce a variety of CF3-substituted dihydronaphthalenes in moderate to good yields, relying on the construction of C(sp2)-CFsub

The reaction of methylenecyclopropanes (MCPs) with tetrahydrofuran (THF) proceed smoothly in the presence of AgOC(O)CF3 and electrophilic halogenation reagents to give the corresponding 4-(3-halobut-3-enyloxy)butyl 2,2,2-trifluoroacetate derivatives in moderate yields through dual cleavage of C-C and C-O bonds under mild conditions. Novel 4-(3-halobut-3-enyloxy)butyl 2,2,2-trifluoroacetate derivatives can be synthesized by AgI-mediated reactions of arylmethylenecyclopropanes with tetrahydrofuran at room temperature through dual cleavage of C-C and C-O bonds. Copyright

The reaction of cyclopropylidene diphenylmethane 1 with an excess of lithium and a catalytic amount of naphthalene (5 mol %) at -20°, followed by addition of an electrophile [E = H2O, D2O, t-BuCHO, Me2CO, Et2CO,

Simple, one-step synthesis of benzylidenecyclopropanes from γ-halopropyl pentachlorophenyl sulfones using a Julia-Kocienski olefination is reported. Georg Thieme Verlag Stuttgart.

Steady state and laser flash photolytic experiments with precursors 6 and 11 revealed that diphenyl substitution affects the lifetime and reaction mode of cyclobutylidene. 2,2-Diphenylcyclobutylidene 3 (τ 0.1 ns) produces methylenecyclopropane 1 via 1,2-carbon in significant preference to the positional isomer 2 or cyclobutene 4. On the other hand, 3,3-diphenylcyclobutylidene 5 (τ = ca. 4 ns) gives 1,2-hydrogen shift product 4 more favorably than 1,2-carbon shift product 2 together with formal carbene dimer 14. MRMP2//MP2 calculations afford useful results to understand the interrelationship among substitution, structure, and reactivity.

Methylenecyclopropane 1 undergoes photochemical rearrangement to 2. Intervention of cyclobutylidene 3 explains not only the rearrangement but also newly obtained products such as cyclobutene 4 and cyclobutylidenecyclobutane 6. Experiments designed to generate cyclobutylidene 3 independently have provided some support for the intermediacy of 3.

Treatment of 1-chlorocyclopropyl phenyl sulfoxides with isopropylmagnesium chloride at low temperature gave magnesium cyclopropylidenes. The reaction of the generated carbenoids with lithium α-sulfonyl carbanions was found to afford alkylidenecyclopropane

Arylidenecyclopropanes react with water in the presence of a catalytic amount of Cu(OTf)2 to afford the corresponding gem-aryl disubstituted homoallylic alcohols in good to excellent yields.

A convenient and efficient method for the synthesis of (Z)-2,4- dihalobutenes, a useful building block in organic synthesis, was reported in good yield by the reaction of alkylidenecyclopropanes and CuX2 (or CuI/I2).

Laser-flash photolysis methods were used to determine Arrhenius functions for cyclizations of the 4,4-diphenyl-3-butenyl (2) and trans-4- phenyl-3-butenyl (5) radicals to the 1,1-diphenylcyclopropylcarbinyl (1) and 1-phenylcyclopropylcarbinyl (4) radicals, respectively. At 20 °C, the cyclization rate constants are 1.7 x 107 and 5.4 x 106 s-1. Equilibrium constants for the two processes were estimated and evaluated with thermochemical data and via computational methods, and Arrhenius functions for the ring-opening reactions of the cyclopropylcarbinyl radicals were calculated. The cyclization reactions of 2 and 5 are strongly enthalpy controlled. Production of radicals 1 and 2 from the corresponding tert- butylperoxy esters in the presence of Et3SnH gave diphenylcyclopropylmethane and 1,1-diphenyl-1-butene from H-atom trapping of radicals 1 and 2 and 4- phenyl-1,2-dihydronaphthalene which derives from the product radical formed by addition of the radical moiety in 2 to the cis-phenyl group. Rate constants for the latter cyclization of 2 and for reactions of radicals 1 and 2 with Et3SnH were obtained from the indirect kinetic studies.

Substituted 6,11-ethano-6,11-dihydrobenzo[b]quinolizinium salts, pharmaceutical compositions containing them, and methods for the treatment of neurodegenerative disorders or neurotoxic injuries utilizing them, wherein the substituted 6,11-ethano-6,11-dihydrobenzo[b]quinolizinium salts have the formula: STR1 wherein: R1, R2, R3, R4, R5, R6, R7, X and p are as defined in the specification.

Reactions of (dimethylamino)phenylsulfoxonium mathylide with triphenylvinylphosphonium salts gave the corresponding cyclopropyltriphenylphosphonium salts (E-form) in high yields, when 1,8-diazabicycloundec-7-ene was used as a base.Reactions of cyclopropyltriphenylphosphonium salts with sodium hydride in the presence of trisamine afforded the corresponding ylides, which further reacted with aldehydes to give alkylidenepropanes in high yields.

Depending on the substituent α-substituted benzylidenecyclopropanes (32) react more or less readily with lithium dust (2% sodium) in diethyl ether whereby a regioselective scission of only the cyclopropane σ-bond cis to the phenyl ring takes place. Upon raising the temperature the primarily formed 1,3-dilithiumorganic compound due to an agostic interaction rearranges by a 1,6-proton shift into a doubly bridged 1,4-dilithio compound. With α-methylbenzylidenecyclopropane (32c) this rearrangement was shown to occur intermolecularly via a trilithiumorganic compound 56. The suggested mechanism of these reductive metalation reactions via a bisected radical anion 87 where the lithium is mainly bound to the cyclopropyl carbon atom and oriented syn to the phenyl ring, was supported by MNDO (geometries) and ab initio (energies) calculations.

Alkylidene cyclopropane derivatives are obtained by reaction of biscyclopropyl titanocene with several types of carbonyl compounds, including aldehydes, ketones and esters. In some cases the isomeric vinyl cyclopropane products are also obtained. Biscyclopropyl titanocene also reacts with alkynes forming, after acidification, the corresponding vinyl cyclopropanes.

Yields obtained from Wittig reactions with cyclopropylidenetriphenylphosporane are greatly improved by addition of the phase-transfer catalyst, TDA-1.

Alkylidenecyclopropanes were readily prepared by thermal decomposition of the potassium or lithium salt of the adduct formed from the treatment of cyclopropyldiphenylphosphine oxide with n-butyl lithium and a carbonyl compound.