Heterodiene syntheses, review

Review Heterodiene synthesis with a,3-unsaturated carbonyl compounds. 

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-... 

In recent years heterodienes, in particular azadienes, have become a useful tool for construction of heterocyclic compounds. In fact, their application toward natural product synthesis through pericyclic processes has been reviewed and their great potential in the field of the alkaloid... 

If nitroalkenes are employed as heterodienes in hetero Diels-Alder reactions instead of nitrosoalkenes, cyclic nitrones are formed. These cycloadducts undergo numerous subsequent reactions, and especially the combination of this hetero Diels-Alder reaction with a 1,3-dipolar cycloaddition is an extremely powerful tool for the synthesis of polycyclic alkaloids. This domino [4+ 2]/[3+ 2] cycloaddition chemistry has been comprehensively reviewed by Denmark and Thorarensen very recently, and this review also covers many hetero Diels-Alder reactions of nitroalkenes being not part of this sequential transformation [5]. Therefore the present article will focus on some selected examples which might highlight the advanced state of the art concerning stereocontrol of these reactions. On the other hand, an insight shall be given into the multitude of polycyclic structures accessible by means of nitroalkene cycloaddition chemistry. 

Cycloadditions involving nitroalkenes as heterodiene have been employed as part of Denmark s domino [4 + 2] / [3 + 2] cycloaddition protocol for the synthesis of natural products. Since also this methodology has just been exhaustively reviewed [5], its value for alkaloid synthesis might be exemplarily demonstrated... 

As discussed in Section 3.15.2.1 (Scheme 3), lf/-phospholes can be transformed into 2/f-phosphoies upon heating. To date, very few stable 2f/-phospholes are known <2004ACR954>. However, a great variety of 2f/-phospholes are accessible using the lf/-phosphole/2/f-phosphole equilibrium, and their heterodiene behavior makes them powerful intermediates for the synthesis of P-heterocycles. Only the results that have appeared since 1996 are presented in this section for a general overview of the chemistry of 27f-phospholes, an excellent review by Mathey is available <2004ACR954>. 

Synthesis of Pyridine Derivatives. Tetrahydropyridine derivatives are readily formed by Diels-Alder cycloadditions of a 1-azadiene with activated alkenes. A review makes clear the many uses of this type of heterodiene in Diels-Alder and other heterocycle-forming processes. An example of tetrahydropyridine synthesis is shown in Scheme 5.4. 

Highly stereoselective inter [4+2]/intra [3+2] cycloadditions of nitroalkenes as heterodienes have been developed by Denmark et al. ° Applications in the synthesis of alkaloids have been reviewed/ ... 

---