Cascade reaction triple

In a collection of insightful pieces of work Enders has incorporated an iminium ion conjugate addition of nitroalkanes to a,P-unsaturated aldehydes into a triple cascade reaction generating up to four contiguous stereocentres in one pot, again indicative of the complexity attainable from superficially simple catalysts and techniques [175-177] (Scheme 46). 

The same cascade reaction of the iodo-triene (296) with Bu3SnH produces tricyclic esters (297a) and (297b) via triple 5-exo-trig ring closure as shown in eq. 3.123. 

Chung has used a combined PK/Diels-Alder cascade reaction to synthesize [5.5.5.6] fenestranes and triquinanes. The first products (181) were obtained in high yield from diendiynes 180 upon reaction with dicobalt octacarbonyl (5%) under 30 atm of CO at 130 °C. The authors think it is more probable that the Diels-Alder reaction occurs after the PKR instead that the diene reacts first with the closer triple bond to form a 1,4-cyclohexadiene that would undergo the PKR (Scheme 53) [ 170]. 

However, oxidations based on addition of O-centered radicals to unsaturated compounds appear to be a highly desirable synthetic goal, especially when the new C—O bond could be formed under the mild conditions that are typical for radical reactions. If this radical addition would involve C = C triple bonds, the resulting reactive vinyl radical would be highly suitable for the promotion of intramolecular cascade reactions. 

However, their intermolecular addition reactions with alkynes are mostly aimed at synthesizing substituted aLkenes, ° and only very few cascade reactions that are initiated by P radical addition to C = C triple bonds have been reported. Renaud and coworkers developed a simple one-pot procedure for the cyclization of terminal alkynes mediated by dialkyl phosphites (Scheme 2.35). In this radical chain procedure, dialkyl phosphite radicals, (R0)2P =0, undergo addition to the C = C triple bond in 190, which triggers a radical translocation (l,5-HAT)/5-eAO cyclization cascade. The sequence is terminated by hydrogen transfer from dialkyl phosphite to the intermediate 194 and regeneration of P-centered radicals. 

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. 

Purely intramolecular cascade reactions using triple bonds as a kind of relay station are well known (Schemes 3-10, 3-16, 3-20, 3-21, 3-22, and 3-24). An inter-intramolecular variant was developed as an elegant access route to calcitriol (60) (Scheme 3-18) [170]. 

Enders et al. elegantly applied diphenylprolinol silyl ether 6a as a catalyst for triple cascade reactions (Scheme 10.18), wherein 6a played the roles ofboth enamine catalyst and iminium catalyst. It should be noted that the four stereocenters were completely controlled[36].Theproposedcatalyticcycleofthe triplecascade isshownin Scheme 10.2. 

The graphitization of diamond may involve thermally-allowed six re-electron concerted processes an electrocyclic reaction converts a six-membered ring in the diamond lattice into three isolated double bonds as shown in Fig. 12. Subsequently, each of the three cyclohexene rings can undergo a retro-Diels-Alder reaction, multiplying the number of double bonds in a triple cascade reaction 23]. 

Double and even triple Heck-Diels-Alder cascade reactions involving bicyclopropyli-dene and 1,4-diiodo- or 1,3,5-triiodobenzene, respectively, have been accomplished. In these sequences, the carbopaUadation across the highly strained alkene is followed by a cyclopropyhnethyl to homoallyl rearrangement with concomitant /3-hydride elimination to yield an allylidenecyclopropane, which subsequently undergoes a smooth [4 + 2] cycloaddition to furnish the spiro[5.2]octene moiety (Scheme 4). ... 

Michael/Michael/Aldol Triple Cascade Reactions... 

The triple Michael/Michael/aldol sequence developed by Enders shown in Scheme 7.8 can probably be considered as one of the most impressive demonstrations of the ability and power of enantioselective organocatalytic cascade reactions for the generation of molecular complexity from very simple and cheap starting materials." In this reaction, a nitroalkene, an enolizable aldehyde and an a,p-unsaturated aldehyde reacted with each other in the... 

Scheme 7.8 Enantioselective triple Michael/Michael/aldol cascade reaction developed by Enders.

Arylrhodium species undergo facile intermolecular 1,2-addition across carbon-carbon triple bonds, with the resulting alkenyl rhodium intermediate providing an entry point for further cascade reactions [121]. As an example, Hayashi applied this concept to the asymmetric synthesis of a number of cycloalkanols 157 starting from ynals 155 and arylboronic acids (Scheme 8.43) [122]. TransmetaUation of the... 

One of the first highly enantioselective examples of multicomponent cascade reactions in orgnocatalysis was developed by Enders et al. [62] in 2006. In this report they describe an asymmetric organocatalytic triple cascade reaction for the construction of tetrasubstituted cyclohexenecarbaldehydes (93) starting from from enals (15), nitroalkenes (28), and enolizable aldehydes (94) (Scheme 10.27). In this work, they did the sequential creation of three bonds by a high enantioselective combination of enamine-iminium-enamine catalysis for a triple cascade reaction. 

SCHEME 10.27. Asymmetric organocatalytic triple cascade reaction. 

A similar cascade reaction was reported by Melchiorre and co-workers [69] in 2008. Initially, this triple cascade reaction between an enolizable aldehyde, 2-cyanoacrylate, and enal consists of the aldehyde addition to a 2-cyanoacrylate derivative (108), promoted by a diphenylprolinol derivative (VII). Next, the resulting adduct reacts with enal via a Michael addition promoted by the same catalyst. Finally, an intramolecular aldol reaction takes place between the formed enamine and the aldehyde, leading to the cyclohexane 109. It should be noticed that the use of an acid as a co-catalyst is cmcial to obtain high levels of stereoselectivity. 

Alachraf MW, Handayani PP, Hiittl MRM, Giondal C, Enders D, Schrader W (2011) Electrospray Mass Spectrometry for Detailed Mechanistic Studies of a Complex Organocatalyzed Triple Cascade Reaction. Org Biomol Chem 9 1047... 

Scheme 8.5 Preferred Heck coupling with the tetrasubstituted alkene bicyclopropylidene (16) (a) single, (b) double, and (c) triple Heck-Diels-Alder cascade reactions [121, 122].

The process could be further extended to a triple cascade reaction consisting of aminopalladation and two subsequent cydizations across different alkenes. 

Enders triple cascade reaction for the formation of three new C—C bonds and providing enantiopure cyclohexane derivatives 152 through reaction of a,p-unsaturated aldehydes 95 with activated methylene compounds 151 using his famous Jprgensen-Hayashi catalyst (5)-97 (Scheme 2.45) [75]. 

Among the triple cascade reaction that involves at least a Michael addition, Cordova et al. developed a tandem asymmetric cyclopropanation/esterification combining amine... 

L. Yadav, A. Rai, A. Singh, S. Singh, Synlett 2011, 335-340. Chiral amine-triggered triple cascade reactions a new approach to functionalized decahydroquinolines. 

Domino or cascade reactions provide valuable approaches, especially to various carbo- and heterocyclic systems with three, four, or even more annelated rings. The Heck reaction has successfully been employed in various inter-inter-, intra-inter-, inter-intra-, as well as all-intramolecular reaction cascades, hi this section, the termination of these processes by alkenes, arenes, and related ir-bond systems such as alkynes and allenes will be described. A cascade Heck reaction is considered to consist of an oxidative addition of a heteroatom-carbon bond to palladium (starter), carbopalladation of a nonaromatic carbon-carbon double or triple bond without immediate dehydropalladation (relay), one, two, or more fimher car-bopalladation(s) of a carbon-carbon double or triple bond, and eventually ensuing dehydropalladation. Crucial for a cascade reaction of this kind to occur is the blockage or retardation of a dehydropalladation at one of the intermediate stages by using 1,1-disubsti-tuted alkenes and appropriately substimted cycloalkenes, bicycloalkenes, or alkynes as relays since they give kinetically stable alkyl- or alkenylpalladium intermediates, respectively. 

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