Tandem reactions synthetic strategies

On the basis of the examples addressed thus far, it is clear that radical reactions can accomplish manifold transformations in organic synthesis. One of the outstanding achievements of synthetic radical chemistry is the development of synthetic strategies based on controlled, tandem radical cyclizations. The efficiency of such strategies is exemplified in the substantial and elegant synthetic work of D. P. Curran and his group.54 The remainder of this chapter will address the concise total syntheses of ( )-hirsutene [( )-1]55 and ( )-A9(12)-capnellene [( )-2]56 by the Curran group. 

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-... 

To rapidly construct complex structures, a recent synthetic strategy uses the Diels-Alder cycloaddition in sequence with another Diels-Alder reaction or with other reactions without isolating the intermediates (domino, tandem, cascade, consecutive, etc., reactions) [4-6]. Scheme 1.2 illustrates some examples. 

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. 

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-... 

This section concludes with a description of tandem synthetic strategies (Section 14.1.6) in which sequential reactions involve combinations of steps such as dendrimer formations combined with cyclic peptides (Section 14.1.6.1), chemoselective cyclization combined with divergent syntheses (Section 14.1.6.3), and many thiol-based reactions and cyclizations (Sections 14.1.6.4—14.1.6.7) J18 ... 

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... 

The presence of a quaternary carbon atom is frequently encountered in sesquiterpene natural products and it often creates a synthetic challenge when two or more quaternary carbon atoms are present contiguously. The synthetic strategies for the construction of quaternary carbon centers involve sigmatropic rearrangements/ intramolecular cycloaddition/ and the reaction of tertiary carbon nucleophiles with a carbon electrophile. Recently, radical cyclization strategies turned out to be very effective for this purpose. For example, Srikrishna utilized the radical cyclization reaction to prepare tricyclo[6.2.1.0 - ]undecane system, which is present in several sesquiterpenes such as zizaenes and prelacinanes, and Chen demonstrated that a tandem radical cyclization approach is an efficient method for constructing the two quaternary carbon centers in the cedrene skeleton. ... 

Synthetic strategy of trehazolin C-6 epimer (253) via tandem aidoi-Witlig reaction... 

Tietze, L. F. Beifuss, U., SequentialTransformations in Organic Chemistry A Synthetic Strategy with a Future. Angew. Chem. Int. Ed. Eng. 1993, 32, 131. Many discussions of tandem reactions can be found in Chem. Rev. 1997, 97(1). 

Parsons PJ, Penkett CS, Shell AJ (1996) Tandem reactions in organic synthesis novel strategies for natural product elaboration and the development of new synthetic methodology. Chem Rev 96 195-206... 

In synthesis of complex molecules, well-designed synthetic strategies involving transition metal catalyzed intra- or intermolecular processes can lead to short cuts to target molecules by so-called tandem or domino reactions [148]. Further progress is expected in the field to accomplish efficient synthesis. 

It is obviously seen in Fig. 1.16, the synthetic strategy of tandem Wessely oxidative dearomatization/IMDA reaction can effectively avoid the flaws of oxidative coupling/IMDA strategy in synthesizing the core structure of Maoecrystal V... 

Based on the concept of tandem reaction, a series of synthetic routes have been developed, including an intramolecular Aldol/Oxa-Michael/Aldol/Lactonization synthetic strategy (see Fig. 1.17). The retrosynthetic analysis indicated that the synthesis starts from compound 1.7.21, which first undergoes an intramolecular Aldol reaction then immediately intramolecular Oxa-Michael reaction to form the tricyclic system. Finally through the intermolecular Aldol reaction and intramolecular esterification reaction, the tetracyclic skeleton of Maoecrystal V can be constructed. And 1.7.21 can be provided by the relatively simple materials 1.7.22 and 1.7.23 through Suzuki cross-coupling reaction. 

Reaction conditions A,A-Dimethylformamide (DMF), room temperature Synthetic strategy One-pot tandem reaction involving transesterification and subsequent Dieckmann cyclization... 

The classical Fischer indole synthesis has persisted as a commonly used procedure due to its working simplicity. However, this method suffers some drawbacks, such as the need for strong acids, poor selectivity with unsymmetrical ketones, and poor functional group tolerance. Huang et al. developed an alternative synthetic strategy for the synthesis of unprotected indoles a tandem ortho-C-H activation and annulation by using triazenyl arenes and alkynes. This reaction involves a ring contraction by a 1,2-Rh shift and an N=N insertion (Eq. (5.12))... 

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