Enantioselective Organocatalyzed Bromolactonizations: Applications in Natural Product Synthesis

Abstract

Asymmetric bromolactonization reactions of δ-unsaturated carboxylic acids have been investigated in the presence of 10 chiral squaramide hydrogen-bonding organocatalysts. The best catalyst enabled the cyclization of several 5-arylhex-5-enoic acids into the corresponding bromolactones with up to 96% ee and in high to excellent chemical yields. The reported catalysts are prepared in a straightforward manner in two steps from dimethyl squarate. The utility of the developed protocol was demonstrated in highly enantioselective syntheses of the sesquiterpenoids (-)-gossoronol and (-)-boivinianin B. Both natural products were obtained in ≥99% enantiomeric excess.

Association of Halogen Bonding and Hydrogen Bonding in Metal Acetate-Catalyzed Asymmetric Halolactonization

“…The catalytic performance of the tri-Zn complex prepared using the best ligand ( L1 ) was examined for asymmetric bromolactonization (Aursnes et al., 2016, Jiang et al., 2012, Jiang et al., 2018, Murai et al., 2010, Tan et al., 2011a, Tan et al., 2011b, Zhou et al., 2010). When the reaction was conducted using N -bromosuccinimide (NBS) at −78 ℃, 5 mol% tri - Zn complex catalyzed the bromolactonization to give the bromolactone 3a in 38% yield with 92% ee (entry1, Table 2).…”

Recent Applications of Asymmetric Organocatalytic Methods in Total Synthesis

“…Compound 347 may also serve as a precursor for the synthesis of the natural product yingzhaosu C ( 349 , Scheme 37). [70] …”

“…[13] In 2016, Hansen and co-workers reported an enantioselective total synthesis of (-)-gossoronol (347) and (À )-boivinianin B (348) (Scheme 37). [70] They utilized the organocatalytic enantioselective bromolactonization reaction of δ-unsaturated carboxylic acids with N-bromophthalimide (342) developed in the paper for converting 341 to 344 using the chiral squaramide 343 as the catalyst. Further transformations of this intermediate afforded compound 347, which is the natural product (À )gossoronol.…”

“…Compound 347 may also serve as a precursor for the synthesis of the natural product yingzhaosu C (349, Scheme 37). [70] In 2019, Hong and co-workers reported enantioselective total synthesis of (+)-arborescidine C (356, Scheme 38). [71] The synthesis started from tryptamine 350 and aldehyde 351, which underwent an organocatalytic enantioselective acyl-Pictet-Spengler reaction under the catalysis of a Jacobsen-type thiourea organocatalyst (352).…”

Solvent and catalyst-free bromofunctionalization of olefins using a mechanochemical approach

“…4 Thus, milder and more user-friendly halogen sources such as N-bromosuccinimide (NBS) and 1,3-dibromo-5,5dimethylhydantoin (DBDMH) are frequently employed in many bromofunctionalization reactions. 5 Well reported examples include bromocyclization reactions such as bromolactonization [6][7][8][9][10][11][12][13][14][15] and bromoetherication [16][17][18][19] as well as the more challenging intermolecular bromoesterication. [20][21][22][23][24][25][26] Because of the high polarity of the N-bromoimide reagents, polar solvents such as N,N-dimethylformamide and acetonitrile are oen required for good solvation which poses difficulties in the purication process.…”