Highly Enantioselective Construction of Strained Spiro[2,3]hexanes through a Michael Addition/Ring Expansion/Cyclization Cascade

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.     

Nickel-catalyzed regio- and stereoselective reductive coupling between methylenecyclopropanes, aldehydes, and triethylborane with retention of the cyclopropane ring

Running rings: The first regio- and stereoselective reductive coupling between methylenecyclopropanes, aldehydes, and triethylborane with retention of the cyclopropane ring was achieved using a nickel-phosphine catalyst (see scheme). The reductive coupling reaction constructed a stereo-defined cyclopropane ring with formation of a quaternary stereogenic carbon center.     

Titanium(IV) chloride-mediated intramolecular ring enlargement of methylenecyclopropanes with propargylic esters: a concise synthesis of bicyclo[4.2.0]oct-5-ene derivatives

Titanium(IV) chloride-mediated intramolecular ring enlargement of methylenecyclopropanes with propargylic esters has been described in this context, affording the corresponding chlorinated bicyclo[4.2.0]oct-5-ene derivatives in moderate to good yields under mild conditions. The E- and Z-methylenecyclopropanes could all be converted to the corresponding bicyclo[4.2.0]oct-5-enes with moderate to high diastereoselectivities.     

Methylenecyclopropanes in [4+1] cycloaddition with enones

A nickel-catalyzed [4+1] cycloaddition of enones with methylenecyclopropanes leading to dihydrofurans was developed. The reaction outcome is attributed to the transformation of methlenecyclopropane, which is incorporated into a five-membered ring as a one-carbon fragment.     

Le cation méthylènecyclopropyle: Etude théorique. Solvolyse des halogénocyclopropènes et des halogénométhylenecyclopropanes

The solvolysis in acid solution of allylic halides and acetates of methylenecyclopropanes and cyclopropylmethanes does not lead to ring opening when there is an ethoxycarbonyl substituent on the ring methylene. Only the cyclopropenyl derivative is obtained. A study of the electronic structure and the geometry of the possible allylic cation intermediate has been carried out using the MNDO method. In addition, the influence of the substituents on the ring opening of this cation has beeen examined. It appears that the ring opening is disfavoured upon substitution of an alkyl group by alkoxymethyl on the ring methylene group.     

PhI(OAc)2-mediated additions of 2,4-dinitrophenylsulfenamide with methylenecyclopropanes (MCPs) and a methylenecyclobutane (MCB)

We report herein stereoselective additions of a nitrene derived from PhI(OAc)₂ and 2,4-dinitrophenylsulfenamide with methylenecyclopropanes (MCPs) and a methylenecyclobutane (MCB) to give the corresponding ring enlargement products, (cyclobutylidene)amide or (cyclopentylidene)amide derivatives, in moderate to excellent yields. The reaction mechanism has been discussed on the basis of control experiments and previous investigation.     

Linear and branched phospha[n]triangulanes

Novel, highly stable, linear and branched mono- and diphospha[n]triangulanes were synthesized in high yields by the CuCl-catalyzed phosphinidene addition to spirocyclopropanated methylenecyclopropanes and bicyclopropylidenes. The effect of spirofusion on the electronic properties of these esthetically attractive phosphacycles is apparent from X-ray single crystal structure analyses, which reveals a tightening of the phosphirane ring on additional spirocyclopropanation, and from the NMR features that show deshielded chemical shifts for the ring-phosphorus and -carbon atoms. Steric factors play a role in the addition reaction when the substrate alkene carries a second sphere of spirocyclopropane rings and causes the formation of 2-phosphabicyclo[3.2.0]heptenes in small amounts. These by-products most probably result from addition of the [PhP(Cl)W(CO)(5)]-Cu-L (L=alkene or solvent) reagent to the spirocyclopropanated bicyclopropylidene to give an intermediate sigma-complex, which subsequently, facilitated by steric factors, undergoes a cyclopropylcarbinyl to cyclobutyl ring expansion followed by a [1,3]-sigmatropic shift.     

Enantioselective catalytic ring expansion of methylenecyclopropane carboxamides promoted by a chiral magnesium Lewis acid

A catalytic enantioselective ring expansion of monoactivated methylenecyclopropanes (MCP) in the presence of N-tosyl aldimines was developed using a chiral bis(oxazoline) ligand-MgI2 complex. After evaluation of ligands and optimization of the reaction conditions, the reaction has been applied to a variety of aromatic and heteroaromatic aldimines providing the corresponding trans-C2,C3-disubstituted methylenepyrrolidines in generally good yields (greater than 52%) and up to 86% ee. [reaction: see text].     

Palladium-catalyzed Inter- and Intramolecular Hydroamination of Methylenecyclopropanes with Amines

The inter- and intramolecular addition of nitrogen pronucleophiles to methylenecyclopropanes proceeds smoothly in the presence of palladium catalyst, giving the corresponding hydroamination products in good to excellent yields. The reaction proceeds mainly through cleavage of a distal bond of methylenecyclopropanes.     

Facile synthesis of 2-alkynyl buta-1,3-dienes via Sonogashira cross-coupling methodology

2-alkynyl buta-1,3-dienes 4 can be synthesized in moderate to high yields by the reactions of the corresponding diiodides 1 derived from methylenecyclopropanes with substituted alkynes 2 via Sonogashira cross-coupling in the catalysis of Pd(PPh3)4/CuI.     

Consecutive reaction of 1-chlorovinyl p-tolyl sulfoxides with [chloro(p-tolylsulfinyl)methyl]lithium leading to the formation of multi-functionalized methylenecyclopropanes

The reaction of 1-chlorovinyl p-tolyl sulfoxides with excess [chloro(p-tolylsulfinyl)methyl]lithium gave methylenecyclopropanes consisting of a chloro(p-tolylsulfinyl)methylene moiety and a (p-tolylsulfinyl)cyclopropylidene moiety. Treating the methylenecyclopropanes with butyllithium resulted in the formation of conjugated enynes.     

Divergent selectivity in MgI(2)-mediated ring expansions of methylenecyclopropyl amides and imides

We report a novel approach to prepare five- and six-membered heterocyclic compounds via a ring expansion of monoactivated methylenecyclopropanes (MCPs) with aldimines and aldehydes in the presence of MgI(2). Monoactivated MCPs behave as homo-Michael acceptors to afford bifunctional vinylogous enolates in the presence of MgI(2). The carbonyl moiety of the monoactivated MCP dramatically influences the reaction site in the dienolate with aryl aldimines and aldehydes as well as the size of the ring. Excellent divergent selectivity to five- vs. six-membered heterocycles is observed: alpha-alkylation/5-exo-tet cyclization (Z = NPh(2)) vs. gamma-alkylation/6-exo-trig cyclization (Z = 2-oxazolidone). Analogously, the reaction of the MCP imide with alkyl aldimines demonstrates the same selectivity by varying the size of electrophile or the reaction temperature. In addition, we observe the first example of the formation of the gamma-alkylation adduct in the reaction of a vinylogous imide enolate with a carbonyl compound.     

Palladium-Catalyzed Hydroalkoxylation of Methylenecyclopropanes

Hydroalkoxylations proceed by a different path than transition metal catalyzed hydrostannations and hydrosilylations. In the reaction of methylenecyclopropanes 1 with alcohols 2 in the presence of Pd(0), the distal bond in the cyclopropane ring is cleaved, and allyl ether 3 is formed selectively. R(1)=n-C(7)H(15), PhCH(2)CH(2); R(2)=H, PhCH(2)CH(2); R(3)=PhCH(2), CF(3)CH(2), Et(3)Si, n-C(4)H(9), etc.     

Carbolithiation of gem-aryl disubstituted methylenecyclopropanes

A novel carbolithiation of gem-aryl disubstituted methylenecyclopropanes was disclosed by the treatment with BuLi in THF at -78 degree C. The corresponding addition products can be obtained in good to high yields by quenching with various electrophiles.     

Photochemistry of cyclopropanes, methylenecyclopropanes, and vinylidenecyclopropanes

This review deals with the recent advances in the photochemistry of cyclopropanes, methylenecyclopropanes, and vinylidenecyclopropanes. cis–trans Photoisomerization of 1,2-diarycyclopropanes via excited singlet and triplet states and radical cations, photochemical polar addition to arylcyclopropanes, and photooxygenation of arylcyclopropanes and methylenecyclopropanes giving cyclic peroxides are described. The new photochemistry of vinylidenecyclopropanes including cis–trans photoisomerization, (3+2) photocycloadditions, and photorearrangements is also discussed.     

Reactivities of methylenetriangulanes and spirocyclopropanated bicyclopropylidenes toward bromine. Relative stabilities of spirocyclopropanated versus methyl-substituted bromonium ions

The bromine additions to methylenecyclopropane (1), bicyclopropylidene (2), and spirocyclopropanated methylenecyclopropanes and bicyclopropylidenes 3-6 in methanol at 25 degrees C proceed essentially with the same rate as those to the corresponding oligomethyl-substituted ethylenes. An increasing number of spiroannelated three-membered rings enhances the rate of bromination and stabilizes the intermediate cyclopropyl bromonium cations against ring opening in the course of bromine addition. Calculations at the B3LYP/6-311G(d,p) level show that unsymmetrical bromonium ions are the intermediates, and that they are stabilized by the spiroannelation with cyclopropane rings. The bromonium ion derived from 1 is less stable by 6.3 kcal mol-1 than that from isobutene. One or two spirocyclopropane rings as in 3 and 4 stabilize the corresponding bromonium ion by 9.6 and 16.4 kcal mol-1, respectively, while one or two alpha-cyclopropyl substituents as in ethenylcyclopropane (7) and 1,1-dicyclopropylethene (8) stabilize the corresponding bromonium ions by 13 and 29 kcal mol-1, respectively. The experimental bromination rates of all the studied alkenes correlate reasonably well (r2 = 0.93) with calculated relative energies of the corresponding bromonium ions. The correlation is even better within the series of methylenecyclopropanes 1, 3, and 4 (r2 = 0.974) and bicyclopropylidenes 2, 5, and 6 (r2 = 0.999). The experimental bromination rates also correlate fairly well with the first ionization energies of the corresponding alkenes 1-12 (with r2 = 0.963) and 13-19 (with r2 = 0.991). The calculated preferred nucleophilic attack of a water molecule at both the C1' and C1 atoms of representative bromonium ions conforms well to the experimentally observed product distribution.     

Ring-opening reactions of methylenecyclopropanes promoted by metal halides

The methylenecyclopropanes (MCPs) react with various metal chlorides or bromides to give the corresponding homoallylic chlorides or bromides in good yields. [reaction: see text]     

Pyrrole,methylenpyrroline und iminocyclopentene durch ubergangsmetallkatalysierte codimerisierung von methylencyclopropanen mit keteniminen

(Ph₃P)₄Pd - or (RO)₃P/Ni(COD)₂ - catalysed [3+2]-cycloaddition of methylenecyclopropanes 1a – 1e with the ketenimines 2a, 2b leads selectively to pyrrols, α -methylene- Δ³ -pyrrolines or iminocyclopentenes depending on the substituents of the imino group and the methylenecyclopropanes.     

Unprecedented Oxycyanation of Methylenecyclopropanes for the Facile Synthesis of Benzoxazine Compounds Containing a Cyano Group

A novel intramolecular oxycyanation of methylenecyclopropanes is reported that proceeds through oxidative cleavage of the N?CN bond and subsequent palladium transfer from N to O of the amide group. A range of substituted benzo[d][1,3]oxazines with a cyano group are readily furnished by this newly developed oxycyanation reaction. Tris(4‐trifluoromethylphenyl)phosphine as a ligand has been found to be crucial to effectively promote the transformation with high chemo‐ and regioselectivity. Moreover, the reaction outcome can be significantly affected by the electronic effect of the acyl group attached to the nitrogen atom of methylenecyclopropanes. When R³ is a chloromethyl group, the pyrrolo[2,3‐b]quinoline derivative is obtained by thermal‐induced [3+2] cycloaddition of methylenecyclopropane to the methanediimine intermediate.     

Ni-catalyzed intramolecular cycloaddition of methylenecyclopropanes to alkynes

Ni-catalyzed intramolecular cycloaddition of methylenecyclopropanes (MCPs) to arkylalkynes via proximal bond cleavage is reported. The reaction provides a facile route for the preparation of cyclopenta[a]indene derivatives.