TY - JOUR
T1 - Regioselective Crossed Aldol Reactions under Mild Conditions via Synergistic Gold-Iron Catalysis
AU - Yuan, Teng
AU - Ye, Xiaohan
AU - Zhao, Pengyi
AU - Teng, Shun
AU - Yi, Yaping
AU - Wang, Jin
AU - Shan, Chuan
AU - Wojtas, Lukasz
AU - Jean, Jonathan
AU - Chen, Hao
AU - Shi, Xiaodong
N1 - Funding Information:
We are grateful to the NSF ( CHE-1665122 ) and the NIH ( 1R01GM120240-01 ) for financial support. This work was supported in part by the University of South Florida Interdisciplinary NMR Facility and the Chemical Purification, Analysis, and Screening core facility, the Department of Chemistry, and the College of Arts and Sciences.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/6/11
Y1 - 2020/6/11
N2 - A synergistic gold-iron (Au-Fe) catalytic system was developed for sequential alkyne hydration and vinyl Au addition to aldehydes or ketones. Fe(acac)3 was identified as an essential co-catalyst in preventing vinyl Au protodeauration and facilitating nucleophilic additions. Effective C–C bond formation was achieved under mild conditions (room temperature) with excellent regioselectivity and high efficiency (1% [Au], up to 95% yields). The intramolecular reaction was also achieved, giving successful macrocyclization (16–31 ring sizes) with excellent yields (up to 90%, gram scale) without extended dilution (0.2 M), which highlights the great potential of this new crossed aldol strategy in challenging target molecule synthesis. Effective construction of the C–C bond is one of the most important tasks in organic synthesis. Whereas aldol condensation is a classic C–C bond-forming transformation, it requires other chemical promoters, such as strong base and reactive acidic catalysts. As a result, the overall transformation is limited in terms of ideal atom economy and environmentally friendly operation. With the discovery of a gold-iron (Au-Fe) synergistic catalysis system, here we describe a new approach to facilitating alkyne hydration and sequential vinyl Au addition to carbonyls. This approach gives the C–C bond-forming products in excellent yields, wide substrate scope, and great functional-group compatibility under mild conditions. This protocol can also be applied to macrocyclization without extended dilution. This C–C bond-forming strategy could facilitate challenging molecule synthesis in chemical, biological, and medicinal research. We report a synergistic gold-iron (Au-Fe) catalytic system to access vinyl Au reactivity by avoiding frequently occurring protodeauration. Fe(acac)3 was identified as an essential co-catalyst, facilitating vinyl Au addition to aldehydes. A broad substrate scope was obtained under mild conditions (room temperature) with excellent regioselectivity and high efficiency (1% [Au], up to 95% yields). This protocol offers a practical solution for achieving macrocyclization (16–31 ring sizes, up to 90%, gram scale) without extended dilution, highlighting the synthetic utility in complex molecular synthesis.
AB - A synergistic gold-iron (Au-Fe) catalytic system was developed for sequential alkyne hydration and vinyl Au addition to aldehydes or ketones. Fe(acac)3 was identified as an essential co-catalyst in preventing vinyl Au protodeauration and facilitating nucleophilic additions. Effective C–C bond formation was achieved under mild conditions (room temperature) with excellent regioselectivity and high efficiency (1% [Au], up to 95% yields). The intramolecular reaction was also achieved, giving successful macrocyclization (16–31 ring sizes) with excellent yields (up to 90%, gram scale) without extended dilution (0.2 M), which highlights the great potential of this new crossed aldol strategy in challenging target molecule synthesis. Effective construction of the C–C bond is one of the most important tasks in organic synthesis. Whereas aldol condensation is a classic C–C bond-forming transformation, it requires other chemical promoters, such as strong base and reactive acidic catalysts. As a result, the overall transformation is limited in terms of ideal atom economy and environmentally friendly operation. With the discovery of a gold-iron (Au-Fe) synergistic catalysis system, here we describe a new approach to facilitating alkyne hydration and sequential vinyl Au addition to carbonyls. This approach gives the C–C bond-forming products in excellent yields, wide substrate scope, and great functional-group compatibility under mild conditions. This protocol can also be applied to macrocyclization without extended dilution. This C–C bond-forming strategy could facilitate challenging molecule synthesis in chemical, biological, and medicinal research. We report a synergistic gold-iron (Au-Fe) catalytic system to access vinyl Au reactivity by avoiding frequently occurring protodeauration. Fe(acac)3 was identified as an essential co-catalyst, facilitating vinyl Au addition to aldehydes. A broad substrate scope was obtained under mild conditions (room temperature) with excellent regioselectivity and high efficiency (1% [Au], up to 95% yields). This protocol offers a practical solution for achieving macrocyclization (16–31 ring sizes, up to 90%, gram scale) without extended dilution, highlighting the synthetic utility in complex molecular synthesis.
KW - SDG3: Good health and well-being
KW - SDG7: Affordable and clean energy
KW - aldol reaction
KW - gold catalysis
KW - iron catalysis
KW - macrocyclization
KW - synergistic catalysis
KW - vinyl gold
KW - β-hydroxy ketone
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U2 - 10.1016/j.chempr.2020.03.014
DO - 10.1016/j.chempr.2020.03.014
M3 - Article
AN - SCOPUS:85086096388
SN - 2451-9294
VL - 6
SP - 1420
EP - 1431
JO - Chem
JF - Chem
IS - 6
ER -