Multicomponent reactions diastereoselective

Other multicomponent reactions are exemplified in the following two schemes. A new highly diastereoselective four-component reaction was developed for the synthesis of dihydropyridones 191 substituted with an isocyanide functionality <06OL5369>, thereby generating a synthetically useful complex isocyanide for use in further reactions. In this strategy, a phosphonate, a nitrile, and an aldehyde are used to generate an azadiene intermediate 192, which is trapped by an isocyanoacetate in the same pot. 

Finally, in the most complex multicomponent reaction involving isocyanides, the 7-CC proposed by Ugi in 1993 [93], a moderate diastereoselectivity, leading to a 2 1 mixture of epimeric thiazolidines 109 was observed. The reaction is a combination between an Asinger condensation, involving an a-mercaptoaldehyde (generated from the a-bromoaldehyde and SH ) and an Ugi-type 4-CC with a monoalkyl car-boxylate as acid component (Scheme 1.38). Although the relative configuration of the major stereoisomer was not demonstrated, it is probably trans, in line with the results of Ugi condensation with chiral thiazolines, reported above in Scheme 1.19. 

Tetrahydroisoquinolonic acids were generated in good to excellent yields by the multicomponent reaction of benzaldehydes, amines, and the cyclic anhydride 65 (Equation 197) <2003T1805>. The key element in this example is the use of ionic liquids and in other examples of the same reaction strategy, the high diastereoselectivity achieved <2005JOC350>. 

The Petasis reaction is a mild multicomponent reaction that allows the conden sation of a boronic acid, an amine, and a carbonyl derivative to generate an allylic amine. Although several diastereoselective Petasis reactions have been reported [106], the first catalytic asymmetric reaction was described in 2008 (Scheme 1.29) [107]. It was shown that the condensation proceeds in high yields and enantiomeric excesses, affording the corresponding protected a vinylglycine derivatives. 

In addition, we have also included chapters that are related to the type of process as organocatalysis, enantio- and diastereoselective reactions, and multicomponent reactions as well as domino processes under microwave irradiation, high pressure, and in water. Finally, two chapters that are more product oriented have been included on the synthesis of compound collections and the synthesis of natural products and analogs. 

Pospisil J, Kumamoto T, Marko IE (2006) Highly diastereoselective silyl-modified sakurai multicomponent reaction. Angew Chem Int Ed 45 3357-3360... 

V. P. Mehta, S. G. Modha, E. Ruijter, K. Van Hecke, L. Van Meervelt, C. Pannecouque, B. Romano, R. V. A. Orru, E. Van derEycken,/ Org. Chem. 2011,76,2828-2839.Amicrowave-assisted diastereoselective multicomponent reaction to access dibenzo[c,e]azepinones synthesis and biological evaluation. 

SCHEME 11.5 Microwave-assisted diastereoselective multicomponent reaction to access dibenzo[c,c]azepinones 46. 

B. Rajarathinam, G. Vasuki, Org. Lett. 2012, 14, 5204—5206. Diastereoselective multicomponent reaction in water synthesis of 2-azapyrrohzidine alkaloid analogues. 

J. PospSil, T. Kumamoto, I. E. Marko, Angew. Chem. Int. Ed. 2006, 45, 3357-3360. Highly diastereoselective silyl-modi-fied Sakurai. Multicomponent reaction. 

Scheme 3.6 Diastereoselective synthesis of functionalized dihydropyridin-2-ones via a Lewis acid-catalyzed ABB multicomponent reaction developed by Maiti.

Muthusamy, S., Gunanathan, C., Nethaji, M. (2004). Multicomponent reactions of diazoamides diastereoselective synthesis of mono- and bis-spirofurooxindoles. Journal of Organic Chemistry, 69, 5631-5637. 

The formation and control of chiral quaternary centers by multicomponent reactions is undoubtedly a challenging task. The combination of a carbometalation reaction of chiral alkynyl sulfoxide 33, followed by a zinc homologation and an allylation in a four-component process, allowed the preparation of homoallylic alcohols or amines 34 bearing tertiary and quaternary stereocenters in a single step with high yields and diastereoselectivities (Scheme 11.13). The zinc carbenoid used in this reaction can be prepared independently or in situ by the reaction of diethyl zinc and diiodomethane. This carbenoid readily homologates the vinyl copper into the allylic species, which reacted diastereoselectively with aldehydes, to give the expected products. The chiral sulfinyl moiety can be easily removed by treatment with alkyllithi-ums, which allows a further functionalization of the carbon skeleton [35]. 

J. Pandey, N. Anand, R.P. Tripathi, L-Proline catalyzed multicomponent reaction of 3,4 dihydro-(2H)-pyran, urea/thiourea, and aldehydes diastereoselective synthesis of hexahydropyranopyrimidinones (thiones). Tetrahedron 65 (2009) 9350-9356. 

Rajesh et al. [232] reported a diastereoselective synthesis of furocoumarins 132 in good yield using IL (Scheme 74). The methodology involved the multicomponent reactions of bromoacetonitrile/phenacylbromide/ethyl bromoac-etate, 4-hydroxycoumarin and substituted aromatic aldehyde in presence of [MBMIM] [OH] and pyridine at 80 °C for 1.5-2h. The authors used IL as catalyst as well as solvent for the reaction. 

The process was catalyzed by copper(I) bromide and proceeded under mild conditions with high diastereoselectivity. The authors noted that no trace of the other diastereomer was observed. It is also worth noting that no chiral ligands (for the copper) were added to the reaction mixture, and yet high selectivity was still obtained. In related work, the propargylamines were generated through a silver-catalyzed multicomponent reaction (Scheme 3.18) [18]. 

Multicomponent one-pot reactions continue to be the focus of heterocyclic synthesis when multi-bonds are formed. Malononitrile condenses with 3-pyridinecarbaldehyde and a ketone to form a substituted bipyridine (Equation 179) <1995JCM146>. In another condensation, with aniline being the ultimate source of the tetrahydroquinoline nitrogen atom, iodine is used as a catalyst in a reaction that was optimized for yield and diastereoselectivity (Equation 180) <2005SL2357>. 

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