Tandem reactions addition-rearrangement

The Rh2(DOSP)4 catalysts (6b) of Davies have proven to be remarkably effective for highly enantioselective cydopropanation reactions of aryl- and vinyl-diazoacetates [2]. The discovery that enantiocontrol could be enhanced when reactions were performed in pentane [35] added advantages that could be attributed to the solvent-directed orientation of chiral attachments of the ligand carboxylates [59]. In addition to the synthesis of (+)-sertraline (1) [6], the uses of this methodology have been extended to the construction of cyclopropane amino acids (Eq. 3) [35], the synthesis of tricyclic systems such as 22 (Eq. 4) [60], and, as an example of tandem cyclopropanation-Cope rearrangement, an efficient asymmetric synthesis of epi-tremulane 23 (Eq. 5) [61]. 

Among all tandem hydroformylation sequences the ones involving additional C,C-bond formations are the most synthetically valuable tandem hydroformylation sequences. These C,C-bonds can be formed by adding nucleophiles, which attack the carbonyl carbon, or by adding electrophiles, which attack the a-position. Furthermore, tandem reactions in which the aldehyde or an aldehyde derivative is involved in sigmatropic rearrangement are described. 

The best catalyst for this transformation was AgSbFg (10 mol%), and (3-ketoesters, malonates, and silyl enol ethers have been used for the nucleophilic addition on the pyridinium intermediate DD. The dihydroisoquinolines 48 have been further used in several reactions in order to assemble the framework of various alkaloids. One example is given in the formation of dihydroisoquinoline 49, bearing a pendent a, 3-unsaturated ketone. Compound 49 can rearrange to the tetracycle 50 (related to the core structure of karachine, Scheme 5.23), using TMSOTf, via a tandem Michael addition-Mannich reaction process (intermediates EE and FF). 

Chuard et al. used allylsulfoxides as precursors of oxygen-centered radicals (Scheme 83) [229]. The Evans-Mislow rearrangement of allylsulfoxides leads to allyl sulfonyl ethers. The authors decided to use those as source of oxygen radicals. In addition, when the allyl sulfoxide was branched on a cyclobutene, the tandem reaction delivered a cyclobutyloxy radical that collapsed and underwent ring expansion in good overall yield. Thus, starting from sulfoxide 283,... 

Evans, P., Taylor, R. J. The epoxy-Ramberg-Backlund reaction a new route to allylic alcohols. Tetrahedron Lett. 1997, 38, 3055-3058. Evans, P., Taylor, R. J. K. Novel tandem conjugate addition/Ramberg-Backlund rearrangements. Syniett 1997,1043-1044. 

Sol 10. (i) The l-alkenyl-4-pentyn-l-ol system (I) undergoes a microwave-assisted tandem oxyanionic 5-exo-dig addition reaction/Claisen rearrangement sequence to give cyclohept-4-enone derivative (II). 

The Overman pyrrolidine synthesis is a tandem reaction, or cascade, used to generate acylpyrrolidine derivatives. This process begins with condensation of an allylic alcohol/ether-containing secondary homoallylic amine with an aldehyde, followed by an aza-Cope rearrangement and subsequent Mannich reaction. Commonly, this reaction is run in refluxing benzene with an acidic additive, such as c/-10-camphorsulfonic acid (CSA). 

A number of vinylation-Claisen rearrangements have been reported as a tandem reaction. Since no additional reagents are required in the thermal Claisen rearrangement, the allyl vinyl ethers can rearrange without isolation. No convenient introduction methods of basically reactive vinyl groups are available for the selective preparation of functionalized vinyl ethers [11,13,14, 22, 24]. 

Tang et al. reported an unexpected tetrahydrothiophene-catalyzed rearrangement/ annulation reaction via a tandem Michael addition/elimination/substitution for the synthesis of chromenes. The products are 27/-chromene- or 4f/-chromene-2-carboxylates, depending on the choice of the base. With K COj 2//-chromene is formed, with Cs COj, 47/-chromene is the major product (Scheme 7.40) [167]. 

Chapter 10 considers the role of reactive intermediates—carbocations, carbenes, and radicals—in synthesis. The carbocation reactions covered include the carbonyl-ene reaction, polyolefin cyclization, and carbocation rearrangements. In the carbene section, addition (cyclopropanation) and insertion reactions are emphasized. Recent development of catalysts that provide both selectivity and enantioselectivity are discussed, and both intermolecular and intramolecular (cyclization) addition reactions of radicals are dealt with. The use of atom transfer steps and tandem sequences in synthesis is also illustrated. 

Allyl aryl ethers undergo accelerated Claisen and [1,3] rearrangements in the presence of a mixture of trialkylalanes and water or aluminoxanes. The addition of stoichiometric quantities of water accelerates both the trimethylaluminum-mediated aromatic Claisen reaction and the chiral zirconocene-catalyzed asymmetric carboalumination of terminal alkenes. These two reactions occur in tandem and, after oxidative quenching of the intermediate trialkylalane, result in the selective formation of two new C-C bonds and one C-0 bond (Eq. 12.70).153 Antibodies have also been developed to catalyze Claisen154 and oxy-Cope155 rearrangements. 

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