Polycyclization Cascade Reactions

Malacria, M. (1996) Selective Preparation of Complex Polycyclic Molecules from Acyclic Precursors via Radical Mediated or Transition Metal-Catalyzed Cascade Reactions. Chemical Reviews, 96, 289-306. 

Diels-Alder reaction of the 1,3,4-oxadiazole with the pendant olefin and loss of N2, the C2-C3 7t bond participates in a subsequent 1,3-dipolar cycloaddition with the carbonyl ylide to generate complex polycycles such as 45 as single diastereomers with up to six new stereocenters. That the cascade reaction is initiated by a Diels-Alder reaction with the alkene rather than with the indole is supported by the lack of reaction even under forcing conditions with substrate 46, in which a Diels-Alder reaction with the indole C2-C3 n bond would be required [26a]. 

A new triethylamine-catalyzed cascade reaction of aromatic aldehydes and propiolates was developed to prepare various benzo[ >]furan-based polycyclic aromatics. Interestingly, the chemical outcome of this process depended on the reaction temperature and was selectively tailored by an appropriate choice of experimental conditions <06OL1241>. 

ArmentroutPB (1999) Gas-Phase Organometallic Chemistry. 4 1-45 Astruc D, Daniel M-C, Ruiz J (2006) Metallodendritic Exo-Receptors for the Redox Recognition of Oxo-Anions and Halides. 20 121-148 Aubert C, Fensterbank L, Gandon V, MalacriaM (2006) Complex Polycyclic Molecules from Acyclic Precursors via Transition Metal-Catalyzed Cascade Reactions. 19 259-294... 

Keywords Absolute configuration, Amines, Amino acids, Carbenes, Cascade reactions, 2-chloro-2-cyclopropylideneacetates. Combinatorial libraries. Cycloadditions, Cyclobutenes, Cyclopropanes, Diels-Alder reactions. Heterocycles, Michael additions. Nitrones, Nucleophilic substitutions, Peptidomimetics, Palladium catalysis. Polycycles, Solid phase synthesis, Spiro compounds. Thiols... 

The various, complex, cascade reactions described above converted simple saturated and aromatic heterocycles into polycyclic pentathiepins and their chlorinated and rearranged derivatives this strikingly illustrates the extensive reactivity of S2CI2 and its complexes with bases, particularly DABCO. This reactivity encompassed dehydrogenation of tetrahydroaromatics, chlorination and sulfuration of aromatics and their conversion into SSCl derivatives. 

A new cascade reaction of aromatic aldehydes with terminal conjugated alkynes produces a range of polycyclic aromatic hydrocarbons.195 The effect of temperature on regioselectivity is discussed. 

The successful utilization of nitrogen-based nucleophiles in the previously described cascade reactions has allowed for the synthesis of complex polycyclic structures from simple and readily available starting materials. The fact that carbamates can participate as nucleophiles has provided the opportunity for development of diastereoselective ring closures onto the halocyclopropane-derived allyl cation. 

Abstract Cascade reactions involving a transition metal-promoted step and a Michael-type addition process have emerged as a powerful tool to construct cyclic and polycyclic structures. In this review, recent advances in this field are presented. The first part is related to cycloaddition reactions based on zwitterionic jr-allylPd complexes. The second part deals with Michael initiated metal-catalyzed cyclofunctionalization reactions of unactivated C C jt-bonds. Parts three and four feature reactions where an initial Michael addition reaction is followed by either a coupling reaction or an electrophilic trapping. Part five is devoted to Michael terminated reactions. 

Complex Polycyclic Molecules from Acyclic Precursors via Transition Metal-Catalyzed Cascade Reactions... 

The carbolithiation of unactivated alkenes has also proven very successful for the synthesis of complex polycyclic systems. This has typically been achieved by reaction sequences utilizing an intramolecular carbolithiation process to generate a variety of carbocycles185 and heterocycles186. To achieve the intermolecular carbolithiation reaction required to initiate a controlled cascade reaction sequence for the generation of indole ring scaffold, Kessler and coworkers44 have expanded the synthetic utility of the styrene... 

Similar methodology was employed to the synthesis of more complex polycyclic ring system, as shown in Scheme 32 <1997TL9069>. The initial alkenyl radical 54, formed by an intramolecular radical 13-< 4t>-dig macro-cyclization, initiated a radical cascade reaction by first reacting at the a-position of the furan ring. 

McCarroll AJ, Walton JC (2001) Angew Chem Int Ed 40 2224 Dhimane A-L, Fensterbank L, Malacria M (2001) Polycyclic Compounds via Radical Cascade Reactions. In Renaud P, Sibi MP (eds) Radicals in organic synthesis, vol 2. WUey, Weinheim, p 350... 

The addition of organometals to non-activated carbon-carbon double or triple bonds, although a breakthrough in polymer chemistry about 70 years ago, has now become an efficient way of creating linear or cyclic substituted structures. The new organometallic thus formed can be quenched by various electrophiles, or can be used, in the case of polyunsaturated systems, to create polycycles via cascade reactions. 

From the selective sampling of cascade reactions for the synthesis of heterocyclic molecules that has been outlined in this chapter, it is clear that virtually any reaction can be incorporated into a tandem sequence. Some cascade sequences increase molecular complexity more than others, but each seems to provide complex heterocyclic structures in a more efficient manner than the corresponding chemistry wherein each intermediate is isolated. Indeed, many of these cascades rapidly construct hetero-polycyclic systems that are difficult to produce in other ways. 

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