Trimethylenemethane equivalents

The intermediates generated from transition metal induced cleavage of methylenecyclopropanes are, in contrast to other trimethylenemethane equivalents, capable of undergoing [3 -I- 2] cycloaddition not only with activated, i.e. electron-deficient alkenes, but also with unsaturated, even nonstrained, hydrocarbons. Some of the reactions summarized in this section are also briefly discussed in Sections 2.2.2.2. and 2.2.2.3.I. because homodi- and homooligomerization of the methylenecyclopropane, as well as [2-1-2] cycloadditions, may efficiently proceed as side reactions of the [3 -f 2] cycloadditions. 

D.iii. Trimethylenemethane Equivalents. Palladium catalysts can be used to convert trimethylsilyl acetate 390 to a trimethylene methane (TMM, 391) equivalent. Reaction with alkenes via [3+2]-cycloaddition (sec. 11.11) generates cyclopentanes (this process constitutes a quinane annulation reaction).229 in this reaction, the trimethylsilyl unit is a carbanion equivalent and acetate is a carbocation equivalent. In one example, Trost reacted 390 and 392 with palladium acetate and triisopropyl phosphite [P(Oi-Pr)3] to generate 393 in... 

Methylene-6-oxabicyclo[3.2.2Inon-8-en-7-ones from 2-pyrones via 4-i-3]-cycloaddition with a trimethylenemethane equivalent... 

When bromoallyl sulfone 50 is converted into its lithio derivative by treatment with lithium diisopropylamide (LDA) at —78°C, it reacts with acrylic esters 51 via Michael-initiated ring closure to provide trisubstituted cyclopentanes 52 with high regio- and stereoselectivity. Thus, 50 can be seen as a trimethylenemethane equivalent (Scheme 22.14). Using enantiomerically pure acrylic esters. 

Developments in the field of stereoselective 1,3-dipolar cycloadditions and their synthetic applications are outlined in Sections 18.2 to 18.4 [22, 23, 28-34]. Subsequently, related [2-i-3]-cycloadditions with 1,3-diradicals and trimethylenemethane equivalents that furnish the corresponding five-membered carbocycles are covered (Section 18.5) [38—41]. The chapter closes with a collection of [2-i-2]-cycloadditions involving ketenes (Section 18.6) [19, 35, 36], photochemical olefin cycloadditions, and Paterno-Biichi reactions (Section 18.7) [36, 37],... 

Stereoselective [3-r 2]-cycloadditions of trimethylenemethane equivalents provide an effective route to substituted five-membered carbocycles not otherwise easily prepared [38-41], Trimethylenemethane diradicals have commonly been accessed from bicyclic diazenes such as 127 not otherwise easily prepared [38, 102], Little showcased that with substrate 129, incorporating an embedded stereocenter, tricyclopentanoid 132 was formed with high yield and diastereoselectivity (dr=99 l. Scheme 18.22) [103], The predominant formation of diastereomer 132 was attributed to a kinetically controlled trapping of the energetically favored intermediate radical 130, in which A] 3 interactions involving the silyloxy substituent are minimized. 

Trimethylenemethane is a special type of alkene that does not exist as the free compound. Various synthetic equivalents to the synthon 43 shown below have been reported. Trost, in particular, has exploited these compounds in 1,3-dipolar cycloaddition reactions.138 139 A metal-bound, isolated trimethylenemethane species was recently reported by Ando (Scheme 6). It resulted from the complexation of an ero-methylenesila-cyclopropene with group 8 carbonyls (Fe, Ru).140,140a The structure was proved by X-ray crystal structure analysis.29Si NMR data were consistent with the -structure shown. 

Acetoxymethyl)allyl]trimethylsilane (5) in the presence of a Pd(0) reagent, for instance, acts as an equivalent of trimethylenemethane in cycloadditions to electron-deficient alkenes such as a,p-unsaturated ketones, esters, nitriles, sulphones and lactones [7] (Scheme 6.6). 

In the same group, Feustel and G. Muller have observed an interesting reaction between two equivalents of the tris(phosphinomethyl)methanol 52 and five equivalents of n-butyl-lithium . Formally, the elimination of lithium oxide leads to the formation of a mixed aggregate of the lithium aUtoxide 53 and the dilithiated trimethylenemethane dianion 54 in the solid state (Scheme 19, Figure 15). The mechanism of the formal elimination of lithium oxide, which could also be part of a further mixed aggregate, has not been cleared up yet. 

Methyleneeyclopentane annelation (9,454-455). The mesylate (2) of 1 has been usedasan electrophilic equivalent of trimethylenemethane for methyleneeyclopentane annelation of a cyclopentanone in a synthesis of coriolin (7).2 Thus, reaction of the enolate of 4, a protected equivalent of 3, reacts with 2 to give 5, which after oxidation to the disulfone is cyclized by fluoride ion to the tricyclic methyleneeyclopentane derivative 6. The product is converted into 7 by several known transformations. 

Sequential nucleophilic and electrophilic alkylations of 1,3-dicarbonyl compounds with a trimethylenemethane zwitterion equivalent lead to [3 + 2]-annulation. The nucleophilic carbonyl alkylation step has been carried out via an indium-mediated allylation in water (Equation (30)).200 Indium-mediated allylation of a-chlorocarbonyl compounds with allyl bromides in aqueous media gives the corresponding homoallylic chlorohydrins, which can be transformed to allyloxiranes (Equation (31)).201 Allylation of the G3 position of the cephem nucleus has been accomplished by indium-mediated allylation reaction in aqueous media (Equation (32)).202... 

By the action of indium, various allylic or propargylic dihalo compounds can be converted to the respective dianion equivalents. In some cases, the reaction with electrophiles proceeds stepwise, whereas in other cases novel diindium reagents are involved. Via an indium-mediated Barbier-type reaction in an aqueous medium, carbonyl compounds react with a trimethylenemethane dianion equivalent to give the corresponding diols (Equation (39)).218... 

Seven procedures describe preparation of important synthesis intermediates. A two-step procedure gives 2-(HYDROXYMETHYL)ALLYLTRIMETH-YLSILANE, a versatile bifunctional reagent. As the acetate, it can be converted to a trimethylenemethane-palladium complex (in situ) which undergoes [3 + 2] annulation reactions with electron-deficient alkenes. A preparation of halide-free METHYLLITHIUM is included because the presence of lithium halide in the reagent sometimes complicates the analysis and use of methyllithium. Commercial samples invariably contain a full molar equivalent of bromide or iodide. AZULENE is a fundamental compound in organic chemistry the preparation... 

Ground-state triplet dicarbenes in photochemical systems have also been extensively studied by ESR. Dowd and coworkers (304) examined the interesting, frequently postulated ground triplet trimethylenemethane obtained by photolysis of either 4-methylene-A -pyrazoline or a single crystal of 3-methylene-cyclobutanone. This triplet molecule is axially symmetrical and the proton hyperfine splittings of 8.9 gauss observed in single-crystal experiments indicate that all protons in the molecule are equivalent when the axis perpendicular to the plane... 

Transition metal chemistry provides an especially rich source of methods for the construction of cyclic compounds. The idea to synthesize 297 from precursor 298 comes from the recognition of 298 as an equivalent to the 1,3-bipolar synthon 298a, trimethylenemethane. It was reasoned that intermediates equivalent to 298a might be formed as transient species and stabilized by complexation with transition metals, e.g. Pd(0). With reagents such as Michael acceptors they can be used for an efficient cyclopentanoannulation. ... 

Trimethylsilylmethylallyl acetate 307a, readily available from CH2— CMeCH20H, provides the equivalent of trimethylenemethane for cycloaddition to electron-deficient olefins in the presence of a (Ph3P)4Pd complex to give methylenecyclopentanes, normally in 50-85% yields... 

In this section, the specific behavior of methylenecyclopropane as a synthetic equivalent for trimethylenemethane is discussed. The variability of reaetivity, as well as ehemo-, regio-and diastereoseleetivity patterns with respect to catalysts and substrates, is demonstrated. Some aspeets of these topics have been reviewed. " ... 

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