Methylene cyclopentanes

Entry R, R-2 MCP r3 Acrylate Yield Spirohexane (%) Methylene- cyclopentane Ratio... 

A hydrosilylation/cyclization process forming a vinylsilane product need not begin with a diyne, and other unsaturation has been examined in a similar reaction. Alkynyl olefins and dienes have been employed,97 and since unlike diynes, enyne substrates generally produce a chiral center, these substrates have recently proved amenable to asymmetric synthesis (Scheme 27). The BINAP-based catalyst employed in the diyne work did not function in enyne systems, but the close relative 6,6 -dimethylbiphenyl-2,2 -diyl-bis(diphenylphosphine) (BIPHEMP) afforded modest yields of enantio-enriched methylene cyclopentane products.104 Other reported catalysts for silylative cyclization include cationic palladium complexes.105 10511 A report has also appeared employing cobalt-rhodium nanoparticles for a similar reaction to produce racemic product.46... 

Cyclization of Bis-Unsaturated Compounds (Section 9.5) (E)-l,l-Bis[(benzyloxy)methyl]-3-methyl-4-[(trimethylsilyl)methylene]cyclopentane [93] To a stirred solution of 4,4-bis-... 

The nature of the ligands on the palladium in ir-allyl complexes can influence the regioselectivity exhibited by soft carbon nucleophiles. ir-Allylpalladium complexes generated from methylenecycloalkanes provide an example of the effect of ligands on regiochemistry. The complexes derived from methylene-cyclopentane and methylenecycloheptane both exhibit exclusive exocyclic addition by the anion of methyl(methylsulfonyl) acetate with triphenylphosphine ligands on the Pd (equation 223). In contrast, the complex derived from methylenecyclohexane yields a 62 38 ratio of exocyclic endocyclic addition (equation 226). 

Vinyltins were used for synthetic purposes in radical addition-elimination sequences. The main limitation comes from the necessity to functionalize the olefin by groups such as esters able to stabilize the transient carbon-centred radical573. Phenyl-substituted systems proved to be reactive as well, whereas methyl- and cyclohexenyl-substituted ones failed to react574. An intramolecular version was developed giving access to methylene cyclopentane units (equation 44)575. 

CsHjo Cyclohexene, methylcyclopentene, methylene cyclopentane, bicyclo--[3.1.0]-hexane, 2-methyl-1, 4-pentadiene 16.0-18.1 g, m, p 927... 

Using this principle, Kibayashi and coworkers [147] have introduced a sequential cyclic carbopalladation-Stille vinylation of enyne compounds. Upon treating the enyne 196 and vinyl tributylstannane with catalytic amounts of Pd2(dba)3 CHCI3 in the presence of AcOH the allyl-substituted methylene cyclopentane 197 was formed in 53% yield (Scheme 80). The subsequent cross-coupling occurs with complete suppression of /M I-climinalion and the Alder-ene product 198 was not detected. Likewise, this sequence was extended to heteroatom-linked enynes and further vinyl tin compounds to provide the heterocyclic analogs 199 in moderate to excellent yields (Scheme 81). 

The consistency of the rate constants determined for the reaction of methylene-cyclopentane with stable carbocation salts in CH2C12 and with... 

The synthesis of functionalized ethylene and propylene containing 1,2-methylene-cyclopropane and 1,2-methylene-cyclopentane units has been achieved, as shown in Scheme 33 for PE.1... 

With Ni(0) catalysts they can react by two different reaction mechanism which give the possibility of synthesizing methylene-cyclopentanes with different substituent patterns (see Eqs. 81, 86 and 87). In Table 11 some of the most interesting results obtained in the preparation of methylenecyclopentanes from [(2-acetoxymethyl)-3-allyl]trimethylsilan or methylenecyclopropanes and electron deficient olefins by this new [3+2]-cycloaddition methodology are summarized. 

The addition of C-H bond of active methine compounds to carbon-carbon double bond in the allene moiety proceeds in intramolecular fashion in the presence of palladium catalyst, leading to the five- or six-membered carbocycles (Eq. 69) [142]. Similar intramolecular carbocyclization can be applied to the methine compounds having the acetylene moiety, leading to the five-membered exo-methylene cyclopentanes in good to excellent yields [143]. 

Cumulenes such as allenes also react with MCP in the presence of palladium(O) catalysts. With allene as substrate, 5-methylenespiro[2.4]heptane (23% yield) can be obtained along with the [3-h2] cycloadduct, l,3-bis(methylene)cyclopentane, in 40% yield. A third product of the reaction, however, is a [3-I-2-I-2] cycloadduct (see Section 2.2.2.3.3.). When the less reactive 1,1-dimethylallene (12) is employed, no [3 -I-2-L2] adduct is formed. Instead, the [3-f 2] adduct, l-methylene-3-(l-methylethylidene)cyclopentane (13), can be obtained in 11-25% yield, depending on the specific catalyst.The major product is 5-methylenespiro[2.4]heptane (7), while 2,5-dimethyl-3-methylenehexa-l,5-diene (14) and dimethylallene trimers are additionally formed. 

Cobalt-catalyzed cyclization of 6-halo-l-hexenes into methylene cyclopentanes has also been reported [175]. Iodo acetal 172a was selected as model substrate. Trimethyl-silylmethylmagnesium chloride (1.0 m THF solution, 1.5 mmol) was added to a mixture of cobalt(II) chloride (0.05 mmol) and l,4-bis(diphcriylphosphino)butane (0.06 mmol) in THF. The resulting mixture was stirred for 5 min and iodo acetal 172 a (0.50 mmol) was then added to the mixture at 0°C. The whole mixture was heated under reflux for 5 min. Aqueous work-up then sihca gel column purification afforded the desired product 173 a in 84% yield in addition to its saturated analog 174 a (Scheme 3.161). 

The zeolite Y-supported, heterogeneous catalyst (54-CuHY) was also used by Hutchings et al. [61] for the enantioselective carbonyl- and imino-ene reactions. In a carbonyl-ene reaction of methylene cyclopentane with ethyl glyoxylate, the heterogeneous catalyst 54-CuHY exhibited superior enantioselectivity (93% ee) compared to the homogeneous catalyst 54-Cu(OTf)2 (57% ee) (Scheme 2.30), due to the confinement effect of the zeolite pores. 

In a similar manner, intramolecular hydrocarboralion can be achieved with C H acidic units using various catalysts,8 81. Thus, acetoacetatc derivatives with an attached alkyne unit using CpCo(CO)2 as catalyst give methylene cyclopentanes with up to 96 4 d.r.78. 

The concept of a bifunctional reagent acting as the three-carbon component in [3 + 2] cycloadditions is an important one, particularly so in catalytic processes (vide infra). Such an approach requires conditions where both functionalities can be tolerated in the same molecule and can be activated sequentially. Attempts to extend this process to a general synthesis of methylene-cyclopentanes by [3 + 2] cycloaddition to silyl enol ethers has been hampered by unsatisfactory regio- and stereoselectivity. 

According to the activation volume data the Diels-Alder dimerization of 1,3-butadiene [39] and o-quinodimethane (Table 2.5, entries (3) and (4), respectively) fall into the same class of concerted processes as those discussed for 1 and 7, while the Diels-Alder dimerization of hexamethylbis(methylene)cyclopentane seems to occur in stepwise fashion. According to the activation volume data summarized in Table 2.6 only the Diels-Alder reaction of 1,3-butadiene with a-acetoxyacrylonitrile seems to proceed concertedly while all other Diels-Alder and homo-Diels-Alder adducts are probably formed in stepwise processes comparable to the corresponding competitive [2 + 2] cycloadditions. Stereochemical investigations of the chloroprene and 1,3-butadiene dimerization using specifically deuterated derivatives confirm the conclusions drawn from activation volume data. In the dimerization of ( )-l-deuteriochloroprene (17) the diastereomeric Diels-Alder adducts ISa-Dz and... 

This strategy has been elegantly applied to the construction of rocaglamid skeleton ]62g] (Eq. 27). Numerous analogous reactions have been carried out [63-65]. The chemistry of dienyl cyclopropanes has been investigated by Oshima [64] (Eq. 28). Singleton [65] has shown that methylene cyclopentanes are obtained in good... 

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