The direct brominative cyclization of methyl farnesate

Abstract

WHEN various acyclic sesqui-, and higher, terpenes are subjected to the controlled action of N-bromosuccinimide (NBS) in aqueous ethylene glycol methyl ether or tetrahydrofuran, terminal monohalogenohydrins are the major products formed in good ~i e l d . l -~ We now report that, in the case of methyl farnesate (I) there are produced concurrently the bicyclic bromo-esters (11) , arising by direct terminal oxidation and cyclization of the acyclic terpene, a process akin to that presumed to operate in the biogenesis of 3-hydroxylated polycyclic terpenes and steroid~.~*5 C02Me By chromatographic meansC02Me.

Stereoselective Halogenation in Natural Product Synthesis

“…For example, van Tamelen and Hessler showed that treatment of methyl farnesoate ( 272 ) with N -bromosuccinimide in aqueous tetrahydrofuran afforded the corresponding bromohydrin 273 as the major product along with only a small quantity of the desired cyclization product 274 (Scheme 58). [106] The addition of an external nucleophile, water in this case, was faster than the cyclization with a poorly nucleophilic pendant alkene. Even in the absence of competing nucleophiles, the basic counterion of the brominating reagent promoted elimination from cationic intermediates prior to the desired cyclization.…”

Enantiospecific Solvolytic Functionalization of Bromochlorides

“…The first report of a racemic bromopolyene cyclization was published more than 50 years ago by van Tamelen and Hessler. 6 Since this seminal report, a variety of reactive brominating reagents have been used to initiate polyene cyclizations, albeit in generally low yields. 7 In fact, a high yielding protocol did not emerge until the popularization of more reactive sulfonium-based brominating agents by the Snyder laboratoy.…”

Selective Bromocyclization of 2‐Geranylphenols Promoted by Phosphite–Urea Cooperative Catalysts

“…Hence, much attention has been devoted to the development of biomimetic bromonium‐induced polyene cyclizations. However, conventional methods that use a standard electrophilic brominating reagent such as Br 2 , N ‐bromosuccinimide (NBS) or 2,4,4,6‐tetrabromocyclohexa‐2,5‐dienone (TABCO) are generally less reactive and generate significant amounts of byproducts . Only a few efficient methods have been developed thus far for bromonium‐induced polyene cyclizations .…”

“…However, conventional methods that use a standard electrophilic brominating reagent such as Br 2 , N-bromosuccinimide (NBS) or 2,4,4,6-tetrabromocyclohexa-2,5-dienone (TABCO) are generally less reactive and generate significant amounts of byproducts. [4][5][6][7][8][9][10][11][12][13][14][15] Only a few efficient methods have been developed thus far for bromonium-induced polyene cyclizations. [16][17][18][19][20] In 2009, Snyder and colleagues reported that Et 2 SBr•SbCl 5 Br (BDSB) is a highly reactive electrophilic bromination reagent and gives the bromocyclization products in good to high yields.…”