Trimethylenemethane -cycloaddition

The success of this carboxylative trimethylenemethane cycloaddition extends to the addition to cyclohexenone. In contrast to the poorly yielding process involving the unsubstituted TMM -Pd complex, a respectable yield of 49 % is obtained here. This is explained by the reduced basicity of the silylated complex, thus leading to fewer side reactions. The reaction is also considered to have a greater degree of concertedness and this becomes apparent in the discussion of chiral Z- and f-olefins in Section 1.6.1.2.3.2. The failure of in situ derived palladium complexes to yield the desired product is attributed to the basic conditions employed which result in double-bond migrations to the endocyclic, conjugated system. 

The bis-(P-naphthyl)pyrrolidinyl-containing ligand also finds use to induce chirality in the trimethylenemethane cycloaddition to imines, which leads to 2-substituted... 

Interactive mechanism for the trimethylenemethane cycloaddition catalytic cycle... 

The reactivity of trimethylenemethane complexes has not been studied extensively. There are, however, a number of catalytic reactions, for which the intermediacy of trimethylenemethane complexes is plausible albeit not proved in all cases, stepwise processes might also be considered [33]. The most prominent examples in this context are palladium-catalyzed trimethylenemethane cycloadditions [34,35] in the presence of a phosphane or phosphite, starting from 2-acetoxymethyl-3-allyltrimethsilane (33), which have been explored in great depth by Trost et al. [36, 37]. 33 undergoes [3-1-2]- as well as [3-H4]cyclizations with electron-poor alkenes or dienes such as 34, respectively, leading to 35 and 36 (Scheme 10.13). 

It is appropriate to mention that the first reported use of In(III) salts in addition reactions was as a cocatalyst in a cycloaddition protocol. In the paper by Trost et al, the Pd-catalyzed trimethylenemethane cycloaddition reaction proceeded with an initial conjugate addition followed by cyclization to form five-membered rings. Addition of In(acac)3 swings the usual 1,4-addition preference to that of a... 

The TT-allylpalladium complexes 241 formed from the ally carbonates 240 bearing an anion-stabilizing EWG are converted into the Pd complexes of TMM (trimethylenemethane) as reactive, dipolar intermediates 242 by intramolecular deprotonation with the alkoxide anion, and undergo [3 + 2] cycloaddition to give five-membered ring compounds 244 by Michael addition to an electron-deficient double bond and subsequent intramolecular allylation of the generated carbanion 243. This cycloaddition proceeds under neutral conditions, yielding the functionalized methylenecyclopentanes 244[148], The syn-... 

Cycloaddition involving the Pd-catalyzed trimethylenemethane (TMM) fragment 63 and the 1.3-diene 61 with an EWG offers a good synthetic method for the hydroazulene skeleton 65. The cydoaddition of trimethylene-... 

Cycloaddition of COj with the dimethyl-substituted methylenecyclopropane 75 proceeds smoothly above 100 °C under pressure, yielding the five-membered ring lactone 76. The regiocheraistry of this reaction is different from that of above-mentioned diphenyl-substituted methylenecyclopropanes 66 and 67[61], This allylic lactone 76 is another source of trimethylenemethane when it is treated with Pd(0) catalyst coordinated by dppe in refluxing toluene to generate 77, and its reaction with aldehydes or ketones affords the 3-methylenetetrahy-drofuran derivative 78 as expected for this intermediate. Also, the lactone 76 reacts with a, /3-unsaturated carbonyl compounds. The reaction of coumarin (79) with 76 to give the chroman-2-one derivative 80 is an example[62]. 

Catalytic asymmetric Diels-Alder reactions are presented by Hayashi, who takes as the starting point the synthetically useful breakthrough in 1979 by Koga et al. The various chiral Lewis acids which can catalyze the reaction of different dieno-philes are presented. Closely related to the Diels-Alder reaction is the [3-1-2] carbo-cyclic cycloaddition of palladium trimethylenemethane with alkenes, discovered by Trost and Chan. In the second chapter Chan provides some brief background information about this class of cycloaddition reaction, but concentrates primarily on recent advances. The part of the book dealing with carbo-cycloaddition reactions is... 

Recent Advances in Palladium-catalyzed Cycloadditions involving Trimethylenemethane and its Analogs... 

The discovery of palladium trimethylenemethane (TMM) cycloadditions by Trost and Chan over two decades ago constitutes one of the significant advancements in ring-construction methodology [1]. In their seminal work it was shown that in the presence of a palladium(O) catalyst, 2-[(trimethylsilyl)methyl]-2-propen-l-yl acetate (1) generates a TMM-Pd intermediate (2) that serves as the all-carbon 1,3-di-pole. It was further demonstrated that (2) could be efficiently trapped by an electron-deficient olefin to give a methylenecyclopentane via a [3-1-2] cycloaddition (Eq. 1). 

Construction of the cyclopentane ring was accomplished by utilization of Trosf s Pd-mediated diastereoselective [3+2] trimethylenemethane (TMM) cycloaddition [4] on the cinnamate 5 having an Evans type chiral auxiliary [4b], The resulting diastereomeric mixture (3 1 at best) of 7a and 7b was separated by careful silica gel column chromatography (7a is less polar than 7b under normal phase). Puri-... 

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. 

Photoelimination of nitrogen from 1-pyrazolines has also been employed in the synthesis of tricyclo[3.2.1.02,4]oct-6-ene,338 prismane,339 quadri-cyclane,340 snoutene ,341 and marasmic acid.342 The trimethylenemethanes 414 have been prepared by photolysis of azoalkanes 415 and characterized spectroscopically.343 Dimerization and cycloaddition to alkenes of these biradicals have been reported.344... 

The palladium-catalyzed hetero-[4 + 3]-cycloadditions reported by Trost and Marrs utilize a metal-complexed trimethylenemethane as the three-carbon component. These complexes react with a,/3-unsaturated imines to produce seven-membered heterocycles in moderate to good yields.84 Two examples of this reaction were reported and are shown in Equations (13) and (14). Only the [4 + 3]-reaction was observed with a,/3-unsaturated imine 76 however, both the [4 + 3]- and the [3 + 2]-modes of reactivity are observed with a,/3-unsaturated imine 79. 

The palladium-catalyzed trimethylenemethane reaction with tropanones was reported in 1987 by Trost and Seoane and is the first example of a [6 + 3]-cycloaddition.130 Chromium-mediated [6 + 3]-cycloadditions of two types have been described-one in which the chromium complex activates the six-carbon component and one in which the chromium complex activates the three-atom component. An example of the first type involves the reaction of a cycloheptatriene-Cr(CO)3 complex with azirines to give cyclic imines in moderate yields (Scheme 40).131... 

The [3+2] cycloaddition of trimethylenemethane (TMM) on the unsaturated lactam 288 worked efficiently with the use ofPd[P(0 Pr)3]4 (generated in situ from palladium(n) acetate (20mol%) and triisopropyl phosphite (160mol%)). The reaction proceeded cleanly in refluxing toluene to afford exclusively the desired cycloadduct 290 in 80% isolated yield (Equation 48) <2003TL5033>. 

Presumably the reaction takes place via the monoallene 225, which can be made the sole isomerization product if the rearrangement is carried out with sodium methoxide in methanol at 65 °C (yield 60%) [76], The intended intramolecular [2 + 2] cycloaddition to the diradical 227, a hybrid of trimethylenemethane and tetramethy-leneethane, could so far not be detected. 

---