Tandem reactions compounds

The key features of the catalytic cycle are trapping of the radical generated after cycliza-tion by an a,P-unsaturated carbonyl compound, reduction of the enol radical to give an enolate, and subsequent protonation of the titanocene alkoxide and enolate. The diaster-eoselectivity observed is essentially the same as that achieved in the simple cyclization reaction. An important point is that the tandem reactions can be carried out with alkynes as radical acceptors. The trapping of the formed vinyl radical with unsaturated carbonyl compounds occurs with very high stereoselectivity, as shown in Scheme 12.21. 

In conclusion, the applicability of the transition metal catalyzed hydroformylation of easily accessible functionalized or non-functionalized unsaturated compounds is expanded by its implementation in reaction sequences, tandem reactions or domino reactions. The hydroformylation can be combined with simple functional group transformations, such as reduction or isomerization, or with C,0-, C,N- and, most importantly, C,C-bond forming reactions. It can be expected that more interesting examples and applications will be presented in the future. 

With type iii-e reactions compounds (71) are formed. A radical tandem reaction initiated by the Kolbe electrolysis of (88) gave tricyclic compounds (89) in a one pot reaction (Scheme 32) [111]. The electrochemical decarboxylation avoids the usually applied toxic tin hydride as reagent and... 

Cycloisomerization represents another approach for the construction of cyclic compounds from acyclic substrates, with iridium complexes functioning as efficient catalysts. The reaction of enynes has been widely studied for example, Chatani et al. reported the transformation of 1,6-enynes into 1-vinylcyclopentenes using [lrCl(CO)3]n (Scheme 11.26) [39]. In contrast, when 1,6-enynes were submitted in the presence of [lrCl(cod)]2 and AcOH, cyclopentanes with two exo-olefin moieties were obtained (Scheme 11.27) [39]. Interestingly, however, when the Ir-DPPF complex was used, the geometry of olefinic moiety in the product was opposite (Scheme 11.28) [17]. The Ir-catalyzed cycloisomerization was efficiently utilized in a tandem reaction along with a Cu(l)-catalyzed three-component coupling, Diels-Alder reaction, and dehydrogenation for the synthesis of polycyclic pyrroles [40]. 

In classical organic synthesis, the individual bonds in the target molecule are usually formed step by step. Starting from relatively simple starting compounds, the structural complexity in the molecule slowly increases in the course of the synthesis. Domino, or tandem, reactions are... 

The reaction of (R)- or (3)-dihydrodinaphthothiepines 23 with an excess of lithium and a catalytic amount of DTBB, under the same reaction conditions shown in Equation (15), after treatment with a carbonyl compound [(Et2CO or (CH2)sCO] or H20 as electrophile, gave enantiomerically pure 127 and 133, respectively. No racemiza-tion occurred during the whole process of the tandem reaction. 

Hydroaminomethylation is a promising reaction to functionalize unsaturated compounds with an amino group [13, 48, 49], The tandem reaction was discovered by Reppe in 1949 and has been further developed in recent years by Eilbracht and Beller. Hydroaminomethylation consists of three consecutive reactions which are carried out in the same reaction vessel [48], The first reaction is hydroformylation which is followed by the condensation with an amine. Hydrogenation of the generated enamine/imine to the amine is the last step. The conditions for hydroaminomethylation are related to the hydroformylation reaction but are not similar due to the two other reactions. The reaction is called an auto-tandem reaction because two of the three reactions need the same catalyst [9] (Scheme 16). 

As a synthetic application to biologically active compounds, eq. 8.19a shows the preparation of nucleoside antibiotics (44a) and (44b). Tyromycin (45) inhibits the leucine and cysteine aminopeptidases, and it can be prepared in good yield from the photolytic treatment of the Af-acyloxy diester with citraconic anhydride, followed by silica gel treatment, as shown in eq. 8.19b [55-60]. Other synthetic applications using intra- and intermolecular tandem reactions were also studied [61, 62]. 

Fig. 7.9 Electrocyclic tandem reaction as generated by RAIN. Rearrangement of a benzocyclobutane 8 into a isochromanone lTvia intermediate compounds 9 and 10.

Tandem (Domino) reactions, in which two or more bond-forming processes result from a single step, are useful for rapid synthesis of complex molecules.138 Functionalized allylsilanes and the related silicon compounds have frequently been used for tandem reactions, because of their ease of synthesis and moderate, controllable reactivity. Recently, much attention has been paid to the use of multifunctional allylsilanes bearing another reactive group on silicon. 

Tandem intramolecular silylformylation-allylation reaction of diallylhydrosilyl ethers derived from homoallyl alcohols is convenient for rapid, stereoselective synthesis of 1,3,5-triols convertible to more oxygen-functionalized compounds (Scheme 12).142,142a,142b 143 [ he second uncatalyzed allylation step would be facilitated by the formation of a strained silacycle intermediate, which has enough Lewis acidity to activate the formyl group. A similar tandem reaction via alkyne silylformylation has been reported.144... 

The organolithium intermediates formed in the tandem reactions, are usually treated with different reagents to produce a variety of products. The way that these kind of reactions are written in Schemes differs from an author to author. Therefore, to be consistent through the chapter, the following convention was adopted E means any reagent that, on reaction with an organolithium compound, delivers an electrophilic moiety, E,... 

The alkyllithium reagents to be used in tandem reactions can be prepared by direct alkylation or by an aldol reaction involving nucleophilic addition of the alkyllithium as the first step. Several complex heteroaromatic compounds, which can serve as pivotal intermediates in synthetic strategy of biologically active species, could be synthesized by this procedure. The preparation of polysubstituted pyridines has been an active research area for many years181. The synthesis of 2-alkyl- or 2-aryl-5-hydrazinopyridines 327 has never been performed directly from pyridine. The reported methods involve several steps... 

This volume, which complements the earlier one, contains 9 chapters written by experts from 7 countries. These include a chapter on the dynamic behavior of organolithium compounds, written by one of the pioneers in the field, and a specific chapter on the structure and dynamics of chiral lithium amides in particular. The use of such amides in asymmetric synthesis is covered in another chapter, and other synthetic aspects are covered in chapters on acyllithium derivatives, on the carbolithiation reaction and on organolithi-ums as synthetic intermediates for tandem reactions. Other topics include the chemistry of ketone dilithio compounds, the chemistry of lithium enolates and homoenolates, and polycyclic and fullerene lithium carbanions. 

Yen and co-workers [155] have described a one-pot MCR for the synthesis of 4,5-dibenzylidene octahydroacridines 107 in high yields. A tandem reaction was performed with three equivalents of an aromatic aldehyde and two equivalents of 4-alkylcyclohexanone in NH4OAC/ACOH applying a domestic microwave oven. Except for one example, most of the reported compounds were obtained in moderate to good yields (Scheme 83). 

The enyne bicyclization-carbonylation tandem reaction is of great interest to synthesize various organic compounds. Possible mechanisms have been proposed as follows (Scheme 27). 

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