Cycloadditions Bradsher

The 2,7-naphthyridine system 53 (Scheme 8.4.18) was combined with 2,4-dinitrochlorobenzene and 2-amino glycerol for in situ reaction of the resulting Zincke salt. The resulting naphthyridinium 54 was trapped by Bradsher cycloaddition with (Z)-vinyl ether 55, providing tetracycle 56 (X-ray) upon internal addition of one of the diastereotopic hydroxymethyl groups to the resulting iminium. This approach was also extended to the use of chiral 2,7-naphthyridinium salts, prepared via the analogous Zincke process. ... 

Isoquinolinium 369 and [2,7]naphthyridin-2-ium 371 salts have also been used for the preparation of 2,3,8,8a-tetrahydro-57/-oxazolo[3,2-tf]pyridine derivatives (Scheme 98) addition of Grignard reagents to 369 is followed by a spontaneous cyclization to 370 <1998JOC1767> while an asymmetric version of the Bradsher cycloaddition between 371 and chiral enol ether 372 gives 373 in good yield and selectivities <1996TL7019>. 

Cationic Polar Cycloaddition by Charles K. Bradsher, Volume 16,... 

Langlois and co-workers have developed a Bradsher cycloaddition route, involving a [2,7]naphthyridinium salt toward the tricyclic core of manzamine A (Scheme 71) <1995TL9475, 1998TL837, 2000TL9251>. 

In addition to electrophilic functionalization, the 5,6-double bond of the adducts (see (222)) is reported to undergo high-pressure [4 + 2]-cycloaddition with jV-(2,4-dinitrophenyl)isoquinolinium chloride (223) (Bradsher cycloaddition) to afford the naphthol-substituted isoxazoline (224) (Equation (61)), which was used for the total synthesis of nogalamycin analogues <92JOC644>. 

Heterocyclic systems with one heteroatom. Condensed heteroaromatic cations are reactive in [2 + 4] cycloaddition reactions with inverse electron demand. For instance, 2-benzopyrylium salts 403 react with vinyl ethyl ether to afford naphthalene derivatives 405 in good yields via initial adducts 404 <1990KGS315>. Similar transformations (Bradsher reaction) are also known for isoquinolinium salts <1984CC761>. 

Scheme 32. Synthesis of the protected enediol 124 by Bradsher cycloaddition [94]...

Using a Zincke-Bradsher convergent strategy for the synthesis of the ABE tricyclic core of Manzamine A, Magnier and Langlois reported the use of aqueous conditions to achieve, in one pot, the preparation of a naphthylpyridi-nium salt intermediate which underwent an inverse electron demand heterocyclic Diels-Alder cycloaddition with either ethyl vinyl ether or (Z)-l-ethoxy-... 

Retrosynthetic analysis leads a new strategy in the synthesis of the ABC core using a Bradsher cycloaddition [83]. Cleavage of the resulting oxazolidinone ( Scheme 22) and a subsequent series of reactions gave a suitably substituted tricyclic core, which can be used in the synthesis of the pentacyclic skeleton ABCDE. 

Stereoselective Synthesis of the Tricyclic core of Manzamine A. The Bradsher Cycloaddition Route. Magnier, E. Langlois Y. and M6rinne, C. Tetrahedron Lett. 1995, 34, 9475. 

Other references related to the Bradsher cycloaddition are cited in the literature. ... 

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