Reactions tandem

The first tandem reactions forming geminal carbon-carbon bonds were reported in 1991, and the following example is representative. A mixture of 5-iodo-l-pentyne (1 eq.) and p-fluorophenyl isocyanide (5 eq.) in t-butylbenzene containing hexamethylditin (1.5 eq.) was irradiated under nitrogen in a pyrex flask at 150°C for several hours until all of the alkyne had been consumed (followed by H nmr). Standard work up gave a mixture of the cyclopentaquinolines 1 and 2 in 56% yield and 85/15 ratio. 

The mould metabolite herqueinone 1 undergoes facile epimerisation at C-4 to give enantio-isoherqueinone when heated under reflux for one hour with anhydrous potassium carbonate in anhydrous acetone. 

The use of tandem reactions continues to be an efficient method for the construction of complex molecules. While tandem cyclization reactions such as the reaction of do-deca-l,6-dien-ll-yne (29) with Et3B-Ph3SnH to furnish the products (30)-(32) 

ElectrochemicaUy generated NO3 has been reported to add to medium-ring alkynes and alkynones to furnish bicyclic ketones and epoxy ketones, respectively. The postulated mechanism involves the addition of NO3 to the alkyne followed by transannular cyclization/eUmination of N03. 

A series of innovative investigations by Kiyooka and co-workers have introduced the use of tandem reaction processes that commence with a stereoselective aldol addition reaction and are followed by C=0 reduction [13]. A chiral oxazaboroli-dine complex prepared from BH3-THF and A-/ -toluenesulfonyl (L)-valine controls the absolute stereochemical outcome of the aldol reaction. In a subsequent reaction, the /i-alkoxyboronate effects intramolecular reduction of the ester to furnish the corresponding /i-hydroxy aldehyde. 

Cleavage of the cyclopropane ring of a chiral bicyclo[4.1. OJheptanone has been used as a key step in the synthesis of the antifungal agent, (-f)-ptilocaulin [74], 

Compound 74 was obtained when A,A-dimethylaniline and furanone 72 were irradiated in the presence of the Michler s ketone 73. These compounds are formed by tandem radical addition-cyclization. The a-amino alkyl radical 71, produced by 

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Fluoroalkjiations are frequentiy performed indirectly using tandem reactions. Arenes react with sodium borohydride in trifluoroacetic acid to afford otherwise difficult to obtain l,l,l-trifluoro-2,2-diarylethanes. Presumably sodium borohydride reacts initially with the trifluoroacetic acid to produce the trifluoroacetaldehyde or its equivalent, which rapidly undergoes Friedel-Crafts-type condensation to give an intermediate carbinol. The carbinol further alkylates ben2ene under the reaction conditions giving the observed product. The reaction with stericaHy crowded arenes such as mesitylene and durene... 

A more recent development in quinone chemistry has been the tandem reaction sequence. In seeking elegant syntheses of complex molecules, careful orchestration of transformations has become essential. The use of the Thiele-Winter reaction in tandem with arylation gives good yields of pharmacologically interesting heterocycles, such as (62), from 2,5-dihydroxy-l,4-ben2oquinone [615-94-1] and pyridines, where R = H or CH (60). 

Tandem reactions of heterocycles combining Diels-Alder reactions with sig-matropic rearrangements 98S227. 

Tandem reactions combining Diels-Alder reactions with sigmatropic rearrangements in syntheses of heterocycles 98S227. 

A more recent application of the Knoevenagel reaction is its use in domino reactions. The term domino reaction is used for two or more subsequent transformations, where the next reaction step is based on the functionality generated in the preceding step. Such reactions are also called tandem reactions or cascade reactions. 

One-pot tandem reactions, starting v/ith nitroalkenes and allyl alcohols leading to fitnaion-alized tetrahydrofitrans, have been repotted fEq. 8.87. ... 

Intra [4+2]/inter [3+2] This type of tandem reaction nsmg nitroalkenes has n been extensively explored, and one example has been reported fEq 8 111 ... 

Inter [4+2]/intra [3+2] This typeof tandem reaction nsmg nitroalkenes hasbeen expbred most extensively Four subfamilies of tandem cycloaddiQon exist, which anse from the font different pomts of attachment of the dipolarophihc tether They are defined as fused, spiro, and bridged modes, as depicted m Scheme 8 37... 

Tandem reaction strategies can accomplish several synthetic objectives in a single step.6 The rapidity with which they can build up molecular complexity is a most useful and impressive virtue. For example, cation-induced, biomimetic polyolefinic cyclizations7 are among the most productive and atom-economical8 single-step transformations known in organic chemistry. In one of the most spectac-... 

Carbonyl ylides continue to be targets of opportunity because of their suitability for trapping by dipolar addition. High enantiocontrol has been achieved in the process described by Eq. 16 [109], but such high enantioselectivity is not general [110] and is dependent on those factors suggested by Scheme 11. Using achiral dirhodium(II) catalysts, Padwa and coworkers have developed a broad selection of tandem reactions of which that in Eq. 17 is illustrative [111] these... 

Keywords Alkenes Alkynes Carbene complexes Ruthenium Tandem reactions... 

Neuschuetz K., Velker J., Neier R. Tandem Reactions Combining Diels-Alder Reactions With Sigmatropic Rearrangement Processes and Their Use in Synthesis Synthesis 1998 227-255... 

Dell C. P. Cycloaddition in Synthesis Contemporary Organic Synthesis 1997 4 87 Keywords natural products, metal catalyzed, asymmetric reactions, Ionic reactions, transannular reactions, tethered reactions, tandem reactions, benzo-qulnones, quinodimethanes, hefero-Dlels-Alder reactions... 

Figure 10.27 Preparation of aminocyclitol precursors by chemoenzymatic tandem reactions.

Possibility for tandem reactions when using whole organisms... 

Experimental studies, combined with thermodynamic analysis, indicate that the CTA hydropurification process is a complex reaction system including both parallel and tandem reactions wherein 4-CBA hydrogenation is exothermic and its paralleled decarbonylation is endothermic. 

NHC-Pd(ll) complexes have also been used in tandem reactions involving a Sonogashira couphng and hydroalkoxylation of the resulting alkyne for the synthesis of benzofurans [131] as well as sequential Heck-Sonogashira couphngs [132] (Scheme 6.44). 

Parsons, P.J., Penkett, C.S., Shell, A.J. (1996) Tandem Reactions in Organic Synthesis Novel Strategies for Natural Product Elaboration and the Development of New Synthetic Methodology. Chemical Reviews, 96, 195-206. 

Rejzek, M., Stockman, R.A., van Maarseveen, J.H., Hughes, D.L. (2005) Combining Two-Directional Synthesis and Tandem Reactions Desymmetrisation by Intramolecular Cycload-dition/Triazoline Fragmentation. Chemical Communications, 4661 662. 

The vinyl lithium reagents generated in the Shapiro reaction can be used in tandem reactions. In the reaction shown below, a hydroxymethyl group was added by formylation followed by reduction. 

The following syntheses were carried by short tandem reaction sequences starting with the Diels-Alder reaction shown. Show the reagents and approximate reaction conditions required to complete the transformation. 

A portion of the side chain of calyculin was prepared by a tandem reaction sequence that combined an alkenylzinc reagent with 2-bromoethenylboronate, followed by Suzuki coupling with a vinyl iodide in the same pot.230... 

Carbonylation can also be carried out as a tandem reaction in intramolecular Heck reactions. 

Section 10.1.2.2 describes another tandem reaction sequence involving a carbonyl-ene reaction. 

Radical reactions used in synthesis include additions to double bonds, ring closure, and atom transfer reactions. Several sequences of tandem reactions have been developed that can close a series of rings, followed by introduction of a substituent. Allylic stannanes are prominent in reactions of this type. 

For clarification, individual transformations of independent functionalities in one molecule - also forming several bonds under the same reaction conditions -are not classified as domino reactions. The enantioselective total synthesis of (-)-chlorothricolide 0-4, as performed by Roush and coworkers [8], is a good example of tandem and domino processes (Scheme 0.1). I n the reaction of the acyclic substrate 0-1 in the presence of the chiral dienophile 0-2, intra- and intermolecular Diels-Alder reactions take place to give 0-3 as the main product. Unfortunately, the two reaction sites are independent from each other and the transformation cannot therefore be classified as a domino process. Nonetheless, it is a beautiful tandem reaction that allows the establishment of seven asymmetric centers in a single operation. 

Recently, Denmark and coworkers have developed a new strategy for the construction of complex molecules using tandem [4+2]/[3+2]cycloaddition of nitroalkenes.149 In the review by Denmark, the definition of tandem reaction is described and tandem cascade cycloadditions, tandem consecutive cycloadditions, and tandem sequential cycloadditions are also defined. The use of nitroalkenes as heterodienes leads to the development of a general, high-yielding, and stereoselective method for the synthesis of cyclic nitronates (see Section 5.2). These dipoles undergo 1,3-dipolar cycloadditions. However, synthetic applications of this process are rare in contrast to the functionally equivalent cycloadditions of nitrile oxides. This is due to the lack of general methods for the preparation of nitronates and their instability. Thus, as illustrated in Scheme 8.29, the potential for a tandem process is formulated in the combination of [4+2] cycloaddition of a donor dienophile with [3+2]cycload-... 

Keywords Immobilization, functionalization, SBA-15, enzyme tandem reaction. 

Tandem reaction of aromatic aldehydes with electron-deficient acetylenes and dialkyl acetylenedicarboxylates in the presence of I it iN led to the formation of fully substituted furans in moderate yields. One appropriate example is shown below <06EJOC5174>. 

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