Transition Metal-Catalyzed Cyclizations

Although details of the metal-mediated cycloaddition chemistry of arynes are well known [110], the use of arynes was for a long period of time restricted to stoichiometric reactions. An excellent example of this is the [2-I-2-I-2] cycloaddition reaction developed by Bennett and Wenger [111], in which one of the participating triple bonds is a nickel-benzyne complex that reacts with 2 equiv. of an alkyne to generate substituted naphthalenes (Equation 12.50). The development of new methods of generating arynes under mild conditions has led to the exploitation of arynes in metal-catalyzed cycloaddition reactions. 

Subsequent extensions of this palladium-catalyzed [2+2-r2] cycloaddition from benzyne to polycychc arynes have opened the door to the synthesis of a number 

When different arynes are generated in the same reaction vessel in the presence of a catalytic amount of a palladium(O) catalyst, a mixture of homotrimers (208 and 211b) and heterotrimers (212 and 213) is obtained (Equation 12.53) [73]. 

The above reaction conditions are only suitable for electron-deficient alkynes. When electron-rich alkynes are used, the corresponding phenanthrenes are obtained in only low yields (up to 34%). At about the same time, the Yamamoto group independently developed a palladium-catalyzed cotrimerization of benzyne with alkynes [118] where the yields of phenanthrene products generated from electron-rich alkynes could be dramatically increased to 59% in the presence of a Pd(OAc)2/P(o-tolyl)3 catalyst system. This process was, however, later shown to proceed through a Pd(0) insertion-carbopalladation process, rather than a free benzyne process [119]. 

The catalyst Pd2(dba)3 also successfully promotes the [2+2+2] cocyclotrimeriza-tion of arynes with suitably functionalized benzodiynes, affording benzo[fe]fluorenones in moderate yields (Equation 12.54) [120]. The best result was achieved when the electron-deficient diyne 222 was employed, when the corresponding benzo[fe]fluorenone 223 was obtained in 54% yield. 

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Transition-Metal Catalyzed Cyclizations. o-Halogenated anilines and anilides can serve as indole precursors in a group of reactions which are typically cataly2ed by transition metals. Several catalysts have been developed which convert o-haloanilines or anilides to indoles by reaction with acetylenes. An early procedure involved coupling to a copper acetyUde with o-iodoaniline. A more versatile procedure involves palladium catalysis of the reaction of an o-bromo- or o-trifluoromethylsulfonyloxyanihde with a triaLkylstaimylalkyne. The reaction is conducted in two stages, first with a Pd(0) and then a Pd(II) catalyst (29). 

Transition metal-catalyzed cyclizations of heterocycles accompanied by multiple bonds migration 98SL1. 

Transition metal-catalyzed cyclizations accompanied by multiple bond migration with formation of heterocycles 98SL1. 

Dienes are less reactive toward transition metals than enynes and diynes, and perhaps for this reason, the development of effective catalyst systems for the cyclization/hydrosilylation of dienes lagged behind development of the corresponding procedures for enynes and diynes. The transition metal-catalyzed cyclization/hydrosilylation of dienes was first demonstrated by Tanaka and co-workers in 1994. Reaction of 1,5-hexadiene with phenyl-silane catalyzed by the highly electrophilic neodymium metallocene complex Cp 2NdCH(SiMe2)3 (1 mol%) in benzene at room temperature for 3 h led to 5- ///76 -cyclization and isolation of (cyclopentylmethyl)phenylsilane in 84% yield (Equation (15)). In comparison, neodymium-catalyzed reaction of 1,6-heptadiene with phenylsilane led to 5- X(9-cyclization to form (2-methylcyclopentylmethyl)phenylsilane in 54% yield as an 85 15 mixture of trans. cis isomers (Equation (16)). 

Processes include the Fischer indole synthesis from arylhydrazones and related sigmatropic syntheses, reductive evclizations of nitni compounds, the Madelung synthesis from anilides and related base-cululyxed condensations. and transition-metal catalyzed cyclizations,... 

Scheme 12.10. Transition-metal-catalyzed cyclization of an allenylthiocarbinol.

Transition metal-catalyzed cyclizations leading to formation of a new CO bond provide a particularly useful approach to dihydrofurans . For example, a high-yielding method for the synthesis of 2,3-dihydrofurans is provided by a ruthenium-catalyzed oxidative cyclization of 4-penten-l-ols (Scheme 64) <2003CL24>. 

The classical routes to 2//-pyran-2-ones (-pyrones) are illustrated in Scheme 124 . Additional examples include various transition metal-catalyzed cyclizations , e.g., the palladium-catalyzed reaction of -chloroacrylates with internal alkynes (Scheme 125) <2001NJC179> and the coupling of tributyl-stannyl allenes with (Z)—iodoacrylic acid (Scheme 126) <2005JOC6669>. 

The intramolecular Heck reaction and similar transition metal-catalyzed cyclizations are commonly used in organic synthesis as illustrated by the preparation of 3-cyanoindole 63 (Scheme 38) <2004BMC2867>. Similar Heck cyclizations have also been employed in the syntheses of tryptophan derivatives <1996T14975>. Solid phase protocols based... 

Classical ring closures (of the FriedelCrafts, Dieckmann, etc., types) can be applied to benzazepine synthesis <1974AHC(17)45>. Particularly useful are approaches to benzazepines based on transition metal-catalyzed cyclizations , as illustrated by the synthesis of 1-benzazepine derivative 149 in high yield by Ru-catalyzed ring-closing metathesis with Grubbs I catalyst (Scheme 87) <2005JOC1545>. 

Various benzazepines can be prepared by transition-metal-catalyzed cyclizations for example, a palladium-catalyzed intramolecular hydroamidation with the alkyne 188 affords the 3-benzazepinone 189 (Scheme 115) <2006TL3811>. 

Michael Addition in Transition-metal Catalyzed Cyclization Reaction... 

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