One-Pot Three-Step Cascade Reactions

The disialyl oligosaccharides obtained are valuable probes for biological studies to understand the biological importance of naturally occurring sialic acid variations. 

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Methyl-l-phenylhept-3-yne-2,6-diol undergoes a one-pot three-step cascade reaction with alkyl and aryl aldehydes to provide 2,4-dihydro-lH-benzo[ isochromans.This two-component cascade reaction promoted by Bp3-OEt2 involves an alkynyl-Prins cyclization, Friedel-Crafts arylation, and dehydrative aromatization (130L4070). Other Prins cascade cycliza-tions of 2-arylethylbut-3-en-l-ol with aliphatic and aromatic aldehydes occur in the presence of Sc(OTf)3 andp-TsOH to prepare trans-fused hexa-hydro-1 H-benzo[ isochromans in good yields and excellent selectivity (Scheme 44) (13EJ01993). 

Radical tandem reactions and in a wider context radical dominos or cascades have attracted a lot of attention because of their intrinsic elegance and the construction of a broad and sometimes unique array of molecular architectures they allow. Contrary to a long-standing idea, efficiency and selectivity requirements can also be met. A good illustration is the one-pot assembly of hnear triquinane 2 from acychc precursor 1 (Scheme 1) [1]. In this ten-elementary radical step process, five C - C bonds are created as well as three quaternary centers and four stereogenic centers, almost all completely controlled. 

An alternative to the 2-halo-carbonyl component is an epoxide or N-tosylaziridine. A cascade sequence was used to bring about formation of the three-membered ring and also reaction with a suitable thioamide in one pot. Whether it is the S-alkylation or the C-3-C-4 bond forming step that occurs first is not known. By producing optically active epoxides/Af-tosylaziridines in situ, the final thiophenes were also optically active (Scheme 69 [112] shows an aziridine sequence). 

In 2007, Hitce and Baudoin reported an elegant procedure to synthesize four-membered benzocarbocycles via a palladium-catalyzed three-step one-pot cascade reaction [14a] (Scheme 6.6). In this work, Baudoin et al. efficiently combined C(sp )—H activation [14b] of 32 with an unusual 4-exo-trig Heck cyclization, affording exo-methylenebenzocyclobutene 33. Finally, ( )-trisubstituted olefins 34 were constructed through a Heck arylation. 

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