TY - JOUR
T1 - Click nucleophilic conjugate additions to activated alkynes
T2 - exploring thiol-yne, amino-yne, and hydroxyl-yne reactions from (bio)organic to polymer chemistry
AU - Worch, Josh
AU - Stubbs, Connor
AU - Price, Matt
AU - Dove, Andrew
PY - 2021/3/25
Y1 - 2021/3/25
N2 - The 1,4-conjugate addition reaction between activated alkynes or acetylenic Michael acceptors and nucleophiles (i.e., the nucleophilic Michael reaction) is a historically useful organic transformation. Despite its general utility, the efficiency and outcomes can vary widely and are often closely dependent upon specific reaction conditions. Nevertheless, with improvements in reaction design, including catalyst development and an expansion of the substrate scope to feature more electrophilic alkynes, many examples now present with features that are congruent with Click chemistry. Although several nucleophilic species can participate in these conjugate additions, ubiquitous nucleophiles such as thiols, amines, and alcohols are commonly employed and, consequently, among the most well developed. For many years, these conjugate additions were largely relegated to organic chemistry, but in the last few decades their use has expanded into other spheres such as bioorganic chemistry and polymer chemistry. Within these fields, they have been particularly useful for bioconjugation reactions and step-growth polymerizations, respectively, due to their excellent efficiency, orthogonality, and ambient reactivity. The reaction is expected to feature in increasingly divergent application settings as it continues to emerge as a Click reaction.
AB - The 1,4-conjugate addition reaction between activated alkynes or acetylenic Michael acceptors and nucleophiles (i.e., the nucleophilic Michael reaction) is a historically useful organic transformation. Despite its general utility, the efficiency and outcomes can vary widely and are often closely dependent upon specific reaction conditions. Nevertheless, with improvements in reaction design, including catalyst development and an expansion of the substrate scope to feature more electrophilic alkynes, many examples now present with features that are congruent with Click chemistry. Although several nucleophilic species can participate in these conjugate additions, ubiquitous nucleophiles such as thiols, amines, and alcohols are commonly employed and, consequently, among the most well developed. For many years, these conjugate additions were largely relegated to organic chemistry, but in the last few decades their use has expanded into other spheres such as bioorganic chemistry and polymer chemistry. Within these fields, they have been particularly useful for bioconjugation reactions and step-growth polymerizations, respectively, due to their excellent efficiency, orthogonality, and ambient reactivity. The reaction is expected to feature in increasingly divergent application settings as it continues to emerge as a Click reaction.
KW - Michael reaction
KW - activated alkynes
KW - conjugate addition reactions
KW - nucleophiles
KW - nucleophilic attack
UR - http://www.scopus.com/inward/record.url?scp=85104982552&partnerID=8YFLogxK
U2 - 10.1021/acs.chemrev.0c01076
DO - 10.1021/acs.chemrev.0c01076
M3 - Article
SN - 0009-2665
VL - 121
SP - 6744
EP - 6776
JO - Chemical Reviews
JF - Chemical Reviews
IS - 12
ER -