Synthesis of Densely Functionalized N-Alkenyl 2-Pyridones via Benzyne-Induced Ring Opening of Thiazolino-Fused 2-Pyridones

TY - JOUR

T1 - Synthesis of Densely Functionalized N-Alkenyl 2-Pyridones via Benzyne-Induced Ring Opening of Thiazolino-Fused 2-Pyridones

AU - Singh, Pardeep

AU - Cairns, Andrew G.

AU - Adolfsson, Dan E.

AU - Ådén, Jörgen

AU - Sauer, Uwe H.

AU - Almqvist, Fredrik

PY - 2019/9/16

Y1 - 2019/9/16

N2 - We report the synthesis of 6-arylthio-substituted-N-alkenyl 2-pyridones by ring opening of bicyclic thiazolino-2-pyridones with arynes. Varied functionalization was used to investigate scope and substituent influences on reactivity. Selected conditions favor thioether ring opening over [4 + 2] cycloaddition and an unusual aryne incorporating ring expansion. Deuterium labeling was used to clarify observed reactivity. Using the knowledge, we produced drug-like molecules with complex substitution patterns and show how thioether ring opening can be used on scaffolds with competing reactivities.

AB - We report the synthesis of 6-arylthio-substituted-N-alkenyl 2-pyridones by ring opening of bicyclic thiazolino-2-pyridones with arynes. Varied functionalization was used to investigate scope and substituent influences on reactivity. Selected conditions favor thioether ring opening over [4 + 2] cycloaddition and an unusual aryne incorporating ring expansion. Deuterium labeling was used to clarify observed reactivity. Using the knowledge, we produced drug-like molecules with complex substitution patterns and show how thioether ring opening can be used on scaffolds with competing reactivities.

KW - Peptides and proteins

KW - Cyclization

KW - Substituents

KW - Ring opening reactions

KW - Reactivity

UR - https://www.scopus.com/pages/publications/85071698867

U2 - 10.1021/acs.orglett.9b02549

DO - 10.1021/acs.orglett.9b02549

M3 - Article

C2 - 31419146

AN - SCOPUS:85071698867

SN - 1523-7060

VL - 21

SP - 6946

EP - 6950

JO - Organic Letters

JF - Organic Letters

IS - 17

ER -