Trimethylenemethane palladium complexes

The addition of the trimethylenemethane-palladium complex to alkenes may proceed by a concerted process or via a stepwise mechanism in which the anion of the 1,3-dipole attacks Michael-fashion to generate an intermediate anion which collapses to form a five-membered ring by attack on the allylpalla-dium complex. This [3 + 2] cycloaddition reaction has been reviewed.128 A number of additional reports of its use have appeared recently.129-134... 

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... 

Evidence clearly indicates that trimethylenemethane (TMM) is not an intermediate in these reactions and establishes, instead, the existence of a trimethylenemethane-palladium complex with dipolar character, viz. (-n3-TMM)PdL2 (T). - ... 

Chloride extraction from [2-(dichloromethyl)-7r-allyl] palladium chloride gave a trimethylenemethane palladium complex (J71)-. 

Some annulation reactions other than those described above have been found. Reaction of 4-ethyl-5-methyl-2-pyrone 509 (Scheme 93) with the trimethylenemethane palladium complex derived from 2-trimethylsilylmethylallyl acetate 307a gives the [4 + 3]-cycloadduct 510 in... 

Acetoxymethyl)-3-(trimethylsilyl)propene (1) is used as a trimethylenemethane precursor in palladium(0)-catalvzed [3 + 2] cycloaddition with electron-deficient alkenes, such as enones, acrylonitriles and a,/ -unsaturaled esters23,26. Mechanistically, this reaction, which gives methylenecyclopentane derivatives 2. is interpreted to proceed via trimethylenemethane-palladium complexes 27,28. 

The acetoxyallylsilane 34 and similar systems react with palladium(O) or palladium(II) to form the trimethylenemethane palladium complexes, which have been employed by... 

Other resnlts obtained by Tsnji s group up to 1987 using allyl carbonates are carbony-lations to afford /3,y-nnsatnrated esters " (Scheme 3) (see Sect. VI.3), cycloadditions of trimethylenemethane palladium complex to afford methylenecyclopentanes (Scheme 3), and cycloadditions of zwitterions to afford substituted vinylcyclopentanes (Scheme 4) (see Sect. V.2.5.2). 2-Butene-1,4-diol dicarbonates afford a variety of cyclic strnctnres by reaction with dinncleophiles nnder Pd(0) catalysis (see Sect. I). The first case reported seems to be the formation of the vinylcyclopropane of Scheme 44" ... 

Pd-catalyzed cyclization was also applied to the stereocontrolled preparation of chiral substituted tetrahydrofurans. The synthesis of optically active tetrahydrofurans was pioneered by Stork and Poirier,who described effective chirality transfer in the Pd-assisted cyclization of y-hydroxy allylic esters. Williams and Meyer deployed a variant of the 0-capture of 7r-allylpalladium complexes in the reactions of substimted trimethylenemethane palladium complexes developed by Trost, using aUylstannane (Scheme 32). A key intermediate 156 in the synthesis of amphidinolide K, a marine nam-ral product, was therefore synthesized starting from enantiopure diastereomer 160. Compound 160 was prepared by in situ transmetallation using the Corey chiral sulfonamide 159 with optically active aUylstannane 157 and then condensation with functionalized aldehyde 158. Formation of the c -2,5-disubstituted tetrahydrofuran 156 occurred with an excellent diastereoselectivity (cis/trans 13 1) and a good yield (88%) from the syn-1,4-precursor 160. 

The first single crystal structure and convenient synthesis of zwitterionic Ti -trimethylenemethane palladium complexes derived from nucleophilic addition of caibanions to an allenyl complex has been reported. ... 

The presence of five-membered rings such as cyclopentanes, cyclopentenes, and dihydrofurans in a wide range of target molecules has led to a variety of methods for their preparation. One of the most successful of these is the use of trimethylenemethane [3 + 2] cycloaddition, catalysed by pal-ladium(O) complexes. The trimethylenemethane unit in these reactions is derived from 2-[ (trimethylsilyl)methyl]-2-propen- 1-yl acetate which is at the same time an allyl silane and an allylic acetate. This makes it a weak nucleophile and an electrophile in the presence of palladium(0). Formation of the palladium 7t-allyl complex is followed by removal of the trimethylsilyl group by nucleophilic attack of the resulting acetate ion, thus producing a zwitterionic palladium complex that can undergo cycloaddition reactions. 

Theoretical studies 225>226> as well as preparative work strongly indicate that the reactive palladium organic intermediate in Reaction 115b and 115c is an unsym-metrical, zwitterionic trimethylenemethane-palladium (TMM-Pd) complex, as formulated in Eq. 117. Moreover, cycloaddition with a cyclic TMM-Pd-precursor revealed that the electron-deficient olefin attacks the TMM-Pd unit from the side away from the metal. This demonstrates that complexation of the olefin with the metal does not occur prior to C—C bond formation 183>. 

The oxidative addition of an allylic acetate having an allylsilane structure (18) to a Pd(0) complex provides a (trimethylenemethane)palladium species (19), which undergoes [3+2] cycloaddition to a variety of electron-deficient olefins (eqs (115) and (116)) [146]. 

Trost s group has developed an annulation reagent (a trimethylenemethane syn-thon) which achieves a nucleophilic addition to an aldehyde followed by a ring closure onto a 7r-allyl palladium complex in the one pot (Fig. 15) [18]. 

Cyclopropenes and mcthylcnccyclopropanes serve as multifunctional reagents in transition metal catalyzed reactions22. Methylenecyclopropanes, via C-C bond cleavage, are also used as trimethylenemethane precursors in transition metal catalyzed [3 + 2] cycloadditions for selective five-membered-ring formation. Low-valent nickel and palladium complexes are used as catalysts. This method has been extensively reviewed 22 and stereoselective applications are fully described in Section D.1.6.1.2.3. 

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. 

In this latter reaction mode, which is observed much more rarely than /3-dehydropal-ladation, a wide variety of ligands can be coupled to each other with the formation of new C—C, C—H, C— N, C—O, and C—Hal bonds. This section does not cover the numerous cascade couplings in which a number of successive intramolecular additions of 2 onto double bonds is eventually completed by /3-dehydropalladationt as well as the numerous [2 -I- 2 -I- 2] and [4 + 2] cyclotri- and cyclodimerizations of alkynes, enynes, and related compounds. " The Pd(0)-catalyzed Cope rearrangement also will not be considered here, as it proceeds via bis(i7 -allyl)palladium(ll) intermediates. The carbopalladation reactions of aUenes, which have been reviewed recently, are covered in Sect. IV.7. (For new examples see also refs. [10]-[12]). On the other hand, the numerous Pd-catalyzed formal [3 + 2] cycloadditions of trimethylenemethane (TMM) complexes may be classified as carbopalladations of alkenes without subsequent dehydropalladation. As the subject of this section has partially been covered in several newly published reviews, " the attention here will be on the most recent and interesting communications. 

The Diels-Alder reaction is a [4 -h 2] cycloaddition between a diene and a dienophile (a substituted alkene or alkyne). It leads to the formation of six-membered rings. Trost has developed a related procedure for making five-membered rings. A trimethylenemethane, briefly trapped as its palladium complex, adds to an alkene, which is activated by an electron-withdrawing group. 

In the presence of a palladium(O) complex, which acts as a catalyst, the precursor eliminates Me3SiOAc to form, fleetingly, a trimethylenemethane palladium... 

Trimethylenemethane derivatives are more elusive species but they have been proposed as intermediates in reactions of palladium complexes with 2-CH2X-l,3-77 -allyl moieties. " Scheme 76 shows one of these transformations that was thoroughly studied, where the substitution of a chloro atom in the allyl by a eyelopentadienyl fragment occurs. A second-order rate law for the decay of the starting allylic complex, along with the analysis of the products obtained with other methyl-substituted allyls, led the authors to propose the mechanism shown. ... 

Versatile [3 + 2]-cydoaddition pathways to five-membered carbocydes involve the trimethylenemethane (= 2-methylene-propanediyl) synthon (B.M. Trost, 1986). Palladium(0)-induced 1,3-elimination at suitable reagents generates a reactive n -2-methylene-l,3-propa-nediyl complex which reacts highly diastereoselectively with electron-deficient olefins. The resulting methylenecyclopentanes are easily modified, e. g., by ozonolysis, hydroboration etc., and thus a large variety of interesting cyclopcntane derivatives is accessible. 

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 reaction of methylenecyclopropanes with transition metal complexes is well known to promote a catalytic a-ir cycloaddition reaction with unsaturated compounds, in which a trimethylenemethane complex might exist71-76. Recently, much interest has been focused on the interaction of strained silicon-carbon bonds with transition metal complexes. In particular, the reaction of siliranes with acetylene in the presence of transition metal catalysts was extensively investigated by Seyferth s and Ishikawa s groups77-79. In the course of our studies on alkylidenesilirane, we found that palladium catalyzed reaction of Z-79 and E-79 with unsaturated compounds displayed ring expansion reaction modes that depend on the (Z) and (E) regiochemistry of 79 as well as the... 

In a variation on the two-component cycloaddition reaction, a [3+3] strategy was reported whereby reaction of enantiomerically pure aziridines, generated from amino acids, with palladium trimethylenemethane complexes leads to a piperidine (Scheme 114). Yields ranged from 63% to 82% and the efficiency of the methodology was demonstrated by the four-step synthesis of (—)-pseudoconhydrin <2001SL1596>. 

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