Tandem reaction sequences

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). 

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... 

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

Synthetic Applications of Tandem Reaction Sequences Involving Hydroformylation... 

Eilbracht P, Schmidt AM (2006) Synthetic Applications of Tandem Reaction Sequences Involving Hydroformylation. 18 65-95 Eisen MS, see Lisovskii A (2005) 10 63-105... 

The Lee group originated rhodium alkenylidene-mediated catalysis by combining acetylide/alkenylidene interconversion with known metal vinylidene functionalization reactions [31], Thus, the first all-intramolecular three-component coupling between alkyl iodides, alkynes, and olefins was realized (Scheme 9.17). Prior to their work, such tandem reaction sequences required several distinct chemical operations. The optimized reaction conditions are identical to those of their original two-component cycloisomerization of enynes (see Section 9.2.2, Equation 9.1) except for the addition of an external base (Et3N). Various substituted [4.3.0]-bicyclononene derivatives were synthesized under mild conditions. Oxacycles and azacycles were also formed. The use of DMF as a solvent proved essential reactions in THF afforded only enyne cycloisomerization products, leaving the alkyl iodide moiety intact. 

Tandem Reaction Sequences Involving Nitrile Oxide Cydizations 1132... 

This method can also be used in tandem reaction sequences, by adding to the crude reaction mixture after completion of the reaction a Grignard reagent (such as ethylmagnesium bromide) to prepare a secondary alcohol (3-undecanol in an overall yield of 53% in the above example). 

Eilbracht P, Baerfacker L, Buss C, Hollmann C, Kitsos-Rzychon BE, Kranemann CL, Rische T, Roggenbuck R, Schmidt A (1999) Tandem reaction sequences under hydroformylation conditions new synthetic applications of transition metal catalysis. Chem Rev 99 3329-3365. doi 10.1021/cr970413r... 

In recent years the use of tandem reaction sequences to create complex cyclic systems in a single reaction has blossomed587-604. Although this area is beyond the scope of the present work, one such process will serve as illustration. Thus, a Michael addition of malonate to... 

Scheme 1.11. Diastereoselective synthesis of a Cgo-scandine conjugate by tandem reaction sequence involving a photoinduced addition of a tertiary amine and a [2 + 2] cycloaddition. The structure of the product includes a noninherently chiral functionalization pattern in addition to stereogenic centers in the alkaloid moiety.

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