TY - JOUR
T1 - Anodic Cyclizations, Densely Functionalized Synthetic Building Blocks, and the Importance of Recent Mechanistic Observations
AU - Krueger, Ruby
AU - Feng, Enqi
AU - Barzova, Polina
AU - Lieberman, Noah
AU - Lin, Song
AU - Moeller, Kevin D.
N1 - Publisher Copyright:
© 2024 American Chemical Society.
PY - 2024/2/2
Y1 - 2024/2/2
N2 - Anodic cyclization reactions can provide a versatile method for converting newly obtained chiral lactols to densely functionalized cyclic building blocks. The method works by first converting the lactol into an electron-rich olefin and then oxidatively generating a radical cation that is trapped by a nucleophile. Historically, such reactions have benefited from the use of less polar radical cations when the trapping nucleophile is a heteroatom and more polar radical cations when the reaction forms C-C bonds. This forced one to optimize underperforming reactions by resynthesizing the substrate. Here, we show that by taking advantage of methods that serve to drive a reversible initial cyclization reaction toward the product, this dichotomy and need to manipulate the substrate can be avoided. Two such methods were utilized: a faster second oxidation step and a mediated electrolysis. Both led to successful cyclizations using a polar radical cation and heteroatom nucleophiles.
AB - Anodic cyclization reactions can provide a versatile method for converting newly obtained chiral lactols to densely functionalized cyclic building blocks. The method works by first converting the lactol into an electron-rich olefin and then oxidatively generating a radical cation that is trapped by a nucleophile. Historically, such reactions have benefited from the use of less polar radical cations when the trapping nucleophile is a heteroatom and more polar radical cations when the reaction forms C-C bonds. This forced one to optimize underperforming reactions by resynthesizing the substrate. Here, we show that by taking advantage of methods that serve to drive a reversible initial cyclization reaction toward the product, this dichotomy and need to manipulate the substrate can be avoided. Two such methods were utilized: a faster second oxidation step and a mediated electrolysis. Both led to successful cyclizations using a polar radical cation and heteroatom nucleophiles.
UR - http://www.scopus.com/inward/record.url?scp=85183109868&partnerID=8YFLogxK
U2 - 10.1021/acs.joc.3c02659
DO - 10.1021/acs.joc.3c02659
M3 - Article
C2 - 38231008
AN - SCOPUS:85183109868
SN - 0022-3263
VL - 89
SP - 1927
EP - 1940
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 3
ER -