Methylenecyclopropanes acidity

Based on the few reported examples, the pattern of ring cleavage that accompanies the ionic hydrogenation of alkylidenencyclopropanes seems to be related to the pattern and degree of substitution on both the ring and the double bond.233 Thus, treatment of l,l-dimethyl-2-methylenecyclopropane with two equivalents of triethylsilane and four equivalents of trifluoroacetic acid for 90 hours at room temperature yields 65% of 2,3-dimethylbutane (Eq. 114).229 Exposure of 1,1-dimethyl-2-isopropylidenecyclopropane to the same ratio of reactants at 50° for 16 hours produces a complex mixture containing 63% of 2,5-dimethylhexane, 18.5% of 2,5-dimethyl-3-hexene, 1.6% of 2,5-dimethyl-2-hexene, and 7% of 2,5-dimethyl-2-hexyl trifluoroacetate (Eq. 115).229... 

An alternative approach to [3 + 2 + 2]-cycloadditions has been reported by Saito and co-workers and involves cleavage of a methylenecyclopropane to produce, after capture with two alkynes, the cycloheptadiene products shown in Scheme 54.144 In a mechanistically distinct [3 + 2 + 2]-reaction, Murakami and Miura report a route to a cycloheptadienone involving the capture of two alkynes initiated by a Suzuki coupling to 2-cyanophenylboronic acid (Equation (32)).145... 

Thus, in a novel synthesis of hypoglycine A (96), hydroxycyclopropanation of ethenyl-acetaldehyde diethyl acetal (93) followed by formal dehydration of the cyclopropanol 94 via its tosylate intermediate gave the methylenecyclopropane species 95, a key precursor to the target amino acid (Scheme 11.26) [92]. 

While thermodynamically, the direct metalation of cyclopropane can be envisioned from a synthetic point of view, this approach has been rarely used. A major obstacle appears to be kinetics which can be overcome by incorporation of a hydroxyl group (see Eq. 16)17). In special cases, such as bicyclo [1.1.0] butane and methylenecyclopropane (Eq. 17) 18) the enhanced thermodynamic acidity is aceom-... 

Since the more highly strained bicyclopropylidene (1) and methylenespiro-pentane (6), both spirocyclopropanated analogs of methylenecyclopropane (2), are even more reactive than the latter, it is to be expected that analogs of the amino acids 287 and 288 containing a bicyclopropylidenyl or a methylenespiro-pentyl moiety would also exhibit biological activities. In fact, the preparations of the amino acids 289 and 290 as well as of the methylenespiropentane amino acid 295 have been reported in the meantime (Scheme 65) [55]. 

Scheme 65. Preparation of bicyclopropylidene and methylenespiropentane analogs 289, 290, and 295 of biologically active amino acids with a methylenecyclopropane moiety [55]...

Since three-membered rings have a number of chemical properties in common with C,C double bonds [51], the spiropentyl analogs of some naturally occurring amino acids containing a methylenecyclopropane moiety [96] are also of potential interest. 

To a solution of methylenecyclopropane (5.4 g, 0.10 mol) in CH2C12 (50 mL) cooled to — 80 °C was added 4-nitroperoxybenzoic acid (18.3 g, 0.10 mol) and the mixture was warmed with stirring. At about 0°C, a highly exothermic reaction occurred and occasional euoling in an ice-waicr bath was necessary. The mixture was stirred at rt overnight, filtered, and the filtrate was distilled under reduced pressure (15 Torr) at rt. The residue (ca. 5 g) was 4-nitrobenzoic acid. The distillate was a solution of oxaspiropentane in CH2C12 which was concentrated by distillation under ordinary pressure. 

Deprotonation of (alkylcyclopropylidenemethyl)cyclopropanes (alkyl = methyl, cyclopropyl) with BuLi and subsequent reactions with various electrophiles afforded the corresponding ring-substituted methylenecyclopropanes (equation 295)365. When the lithiated compounds are treated with C02, carboxylic acids are obtained, together with isomeric lactones. These can be regarded as formal 3+2 adducts of the methylenecyclopropanes with C02 (equation 295)366. 

Nickel(0)-catalyzed codimerization of methylenecyclopropanes with electron-deficient olefines are highly regiospedfic, but show a rather poor stereoselectivity. Thus the asymmetric nickel(0)-catalyzed codimerization of methylenecyclopropanes with the chiral bomane derivatives of acrylic acid leads to the optically active 3-methylenecyclopen-... 

The aminochlorination of methylenecyclopropanes and vinylidenecyclopropanes has been explored with use of FeCT (20 mol%) as a Fewis acid catalyst in acetonitrile under convenient mild conditions. The aziridinium-based mechanism, accounting for... 

An acid-catalysed reaction32 of methylenecyclopropanes [e.g. (22)] with various unactivated and mildly activated arenes forms cyclized products in good yield [e.g. 

Pd(PPh3)4-catalysed isomerization of methylenecyclopropanes in acetic acid proceeds smoothly at 1-substituted or 1,1-disubstituted dienes (Scheme 90). A plausible mechanism is hydropalladation and /3-carbon-Pd elimination followed by /3-hydride elimination, established from a deuterium labelling experiment.133... 

Cazes et al. reported the Pd-catalyzed intermolecular hydroamination of substituted allenes using aliphatic amines in the presence of triethylammonium iodide leading to allylic amines [19]. In a way similar to the Pd-catalyzed hydrocarbona-tion reactions we reported that the hydroamination of allenes [20], enynes [21], methylenecyclopropanes [22], and cyclopropene [10] proceeds most probably via oxidative addition of an N-H bond under neutral or acidic conditions to give allylic amines. The presence of benzoic acid as an additive promotes the Pd-medi-ated inter- and intramolecular hydroamination of internal alkynes [23]. Intramolecular hydroamination has attracted more attention in recent years, because of its importance in the synthesis of a variety of nitrogen-containing heterocycles found in many biologically important compounds. The metal-catalyzed intramolecular hydroamination/cyclization of aminoalkenes, aminodienes, aminoallenes, and aminoalkynes has been abundantly documented [23]. 

Methylenecyclopropanes react with 2-cyclopentenone in the presence of this Ni(0) catalyst, triphenylphosphine and triethylborane (Lewis acid) to form 6-meth-ylenebicyclo[3.3.0]octane-2-ones. 

Lanthanide salts serve as efficient Lewis acid catalysts in the [3+2] cycloaddition of methylenecyclopropanes with activated aldehydes or ketones (Equation 100) <2003TL3839>. 

Methylenecyclopropanes undergo oxidative ring expansion in a two-step sequence peroxy acid oxidation to an oxaspiropentane followed by lithium iodide induced rearrangement yields a cyclobutanone in moderate yield, as illustrated in equation (49). Cyclobutanone is a minor product from the reaction of... 

The yields and regioselectivity of the reactions of substituted methylenecyclopropanes with 2-cy-clopentenone are improved with the use of triethylborane as a Lewis acid co-catalyst (equations 95, 96). No reaction with cyclopentenone is observed in the case of (82) without this co-catalyst. ... 

Trimethylsilyl)methylenecyclopropane (36 equation 15) is usable instead of methylenecyclopro-pane in reactions with electron deficient alkenes involving [PdCp(T) -allyl)]/PPr 3, giving silylated methylenecyclopentanes (37) and (38) in good yields and with better selectivities than those obtained from unsubstituted methylenecyclopropane (26). The trimethylsilyl group can be easily removed by protonolysis with trifiuoroacetic acid. ... 

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