Metallo-ene cyclization

The above concept of catalytic metallo-ene cyclizations (Scheme 36) may also be extended to platinum and nickel, as one would expect in view of previous work on intermolecular nickel-ene reactions (cf. Section 1.2.2.4). 

Moderate enantioselectivity in terms of differentiation between the enan-tiotopic olefin functionality of prochiral ene substrate with planar symmetry was observed by using a chiral palladium complex. The use of a chiral bidentate ligand with a large bite angle [66] is effective for this type of enantioselective catalytic metallo-ene cyclizations. 

Scheme 22. Asymmetric metallo-ene cyclization catalyzed by chiral Pd complex...

The stereochemistry of the metallo-ene cyclization step plays a crucial role in the accessibility of subsequent reaction steps. Thus, only the civ-isomer of the cyclization product can undergo further carbonylative cyclization to form the bicyclic products, while the fram-isorner can Only undergo linear carboxylation 65. Product distribution also depends on the catalyst used. Thus, for selective carbonylative bicyclizations, nickel catalysis, especially Ni(cod)2/1,4-bis(diphenylphos-phino)butane, are more effective than palladium systems, such as Pd(dba)2/triphenylphosphane55. 

Intramolecular substitutions involving an allylsilane moiety as well as following a metallo-ene reaction pattern have been reported. Tandem metallo-ene cyclization and vinylstannane coupling serve to construct cycloalkanes with vicinal alkenyl chains. " ... 

The first example involving a rhodium catalyst in an ene reaction was reported by Schmitz in 1976. An intramolecular cyclization of a diene occurred to give a pyrrole when exposed to rhodium trichloride in isobutanol (Eq. 2) [15]. Subsequently to this work, Grigg utilized Wilkinson s catalyst to effect a similar cycloisomerization reaction (Eq. 3) [16]. Opplozer and Eurstner showed that a n -allyl-rhodium species could be formed from an allyl carbonate or acetate and intercepted intramolecularly by an alkene to afford 1,4-dienes (Eq. 4). Hydridotetrakis(triphenylphosphine)rhodium(l) proved to be the most efficient catalyst for this particular transformation. A direct comparison was made between this catalyst and palladium bis(dibenzylidene) acetone, in which it was determined that rhodium might offer an additional stereochemical perspective. In the latter case, this type of reaction is typically referred to as a metallo-ene reaction [17]. 

The perfect diastereoselectivity observed in these reactions lead to the assumption that they do not proceed via a simple anionic intramolecular cyclization (i.e. carbozincation) as was proposed in earlier61 publications. Cyclizations of non-propargylic substrates15,62 were shown to proceed with significantly lower diastereoselectivity (cis/trans typically 75/25). Thus, in the case of propargylic compounds, e.g. 114, a simple carbozincation process is unlikely to be operative. It was therefore reasoned that the active species in these reactions is not 115-ZnBr but rather its allenic isomer 120, which undergoes a metallo-ene-allene reaction in a chair-like transition state as depicted in equation 5659a. 

Intramolecular metallo-ene reactions are thermodynamically favored and are thus more efficient than the intermolecular versions. The classical distinction of the cyclization modes, suggested by Oppolzer, depends on the carbon of the allylic organometallic (ene-component) to which the alkene or the alkyne (enophile) is linked (equation 77)5,6. 

Two other Ni(CO)4 substitutes, Ni(CO)3PPh3 and Ni(COD)2/dppe, prove to be appropriate for the catalysis of tandem metallo-ene/carbonylation reactions of allylic iodides (Scheme 7)399. This process features initial oxidative addition to the alkyl iodide, followed by a metallo-ene reaction with an appropriately substituted double or triple bond, affording an alkyl or vinyl nickel species. This organonickel species may then either alkoxycar-bonylate or carbonylate and undergo a second cyclization on the pendant alkene to give 51, which then alkoxycarbonylates. The choice of nickel catalyst and use of diene versus enyne influences whether mono- or biscyclization predominates (equations 200 and 201). 

Coverage in this chapter is restricted to the use of alkenes or alkynes as enophiles (equation 1 X = Y = C) and to the use of ene components in which a hydrogen is transferred. Coverage in Sections 1.2 and 1.3 is restricted to ene components in which all three heavy atoms are carbon (equation 1 Z = C). Thermal intramolecular ene reactions of enols (equation 1 Z = O) with unactivated alkenes are presented in Section 1.4. Metallo-ene reactions are covered in the following chapter. Use of carbonyl compounds as enophiles, which can be considered as a subset of the Prins reaction, is covered in depth in Volume 2, Chtqiter 2.1. Addition of enophiles to vinylsilanes and allylsilanes is covered in Volume 2, Chapter 2.2, while addition of enophiles to enol ethers is covered in Volume 2, Chapters 2.3-2.S. Addition of imines and iminium compounds to alkenes is presented in Volume 2, Part 4. Use of alkenes, aldehydes and acetals as initiators for polyene cyclizations is covered in Volume 3, Chapter 1.9. Coverage of singlet oxygen, azo, nitroso, S=N, S=0, Se=N or Se=0 enophiles are excluded since these reactions do not result in the formation of a carbon-carbon bond. 

In contrast, intramolecular versions of the metallo-ene process may be regio- and stereo-selective as well as entropically favored and are thus more efficient, similar to intramolecular ene reactions (Volume 5, Chapter 1.1) and [4 + 2] cycloadditions (Volume 5, Chapter 4.4). This holds for two different modes of cyclization in which the enophile is linked by a suitable bridge, either to the terminal carbon atom C-3 (type I) or to the central carbon aton C-2 (type II) of the metallo-ene unit (Scheme 18). The prc nsity of the cyclized alkylmetal intermediates (F) and (H) for further functionalizations and cycli-zations, involving the metallated and two alkenic sites, offers a considerable potential in organic synthesis. 

The nickel/chromium-catalyzed cyclizations of 1,2,7-trienes (270) to (272) were postulated to proceed via a metal hydride addition to the allene unit of (270X generating an allylmetal intermediate (271) which undergoes a metallo-ene/p-elimination sequence. It is worth noting that these cyclizations can be stereocontrolled by the presence of resident stereogenic centers, as demonstrated by the transformations (273) (274) and (275) (276) (Scheme 57). 

Another facet of the cyclization of secondary organometallic derivatives is the use of d-ethenic allylmetals [61] this has been abundantly reviewed [58] and is considered as a metallo-ene reaction. However, although the ene-allene reaction was disclosed 10 years ago [59] to interpret the formation of a cyclic product by flash pyrolysis of a 2,3,8-nonatriene, the corresponding metallo-ene-allene reaction has received attention only veiy recently in organic synthesis [60]. 

The metallo-ene reaction of the synthetic intermediates cis-M and trans-64 shown in Scheme 8-22 combined witli a carbonylation reaction afforded cyclized esters [94]. 

In another approach, the cyclization is achieved via a metallo-ene reaction (Scheme 8-22) [87]..In this case, the cyclization occurs with anti stereochemistry. 

Keywords Ene reaction, Hetero-Diels-Alder reaction, Ene cyclization, Desymmetrization, Kinetic resolution. Non-linear effect. Asymmetric activation, Metallo-ene, Carbonyl addition reaction, Aldol-type reaction. Titanium, Aluminum, Magnesium, Palladium, Copper, Lanthanides, Binaphthol, Bisoxazoline, Diphosphine, TADDOL, Schiff base. 

In a closely related palladium- or nickel-catalyzed reaction, diene halides, acetates or carbonates 12 can be cyclized via intramolecular metallo-ene reaction of the allylpalladium intermediates. Various subsequent reactions can follow, such as dehydropalladation59 64-122 or car-boxylation and further carbonylativc cyclization to bicyclic products60 65 67. Dicarborative addition reactions of the latter type and their synthetic use have been extensively reviewed 68-69. 

The cyclization of allylic acetates tethered with alkenes has been extensively investigated by Oppolzer, employing a number of transition metals including nickel. The process has been termed a metallo-ene reaction however, the mechanism likely involves a sequence of oxidative addition to generate a jt-aUyl complex, alkene insertion, and P-hy-dride elimination. The process is quite general in scope and provides a very useful method for the preparation of 1,4-dienes such as 46 (Scheme 28). 

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