Reversal of Enantioselectivity in the Conjugate Addition Reaction of Cyclic Enones with the CuOTf/Azolium Catalytic System

Hydroxyamide-functionalized azolium salt (NHC•HI 4) was evaluated for dual enantioselective control in a Cu-catalyzed asymmetric conjugate addition (ACA) reaction. This investigation was based on our previously reported ACA reaction catalyzed using CuOTf combined with NHC•AgI complex 1. It was revealed that the stereocontrol of the catalytic ACA reaction depended on the order of the addition of the substrates. Additionally, the chiral NHC ligand precursors, substrates, the relationship between the catalyst ee (eecat) and product ee (eepro), and halogen counter anion were completely evaluated. These results suggested that the catalytic performance of the CuOTf/4 system was comparable with that of the CuOTf/1 system. Furthermore, to gain knowledge of the Cu species generated using CuOTf and NHC ligand precursor, the reaction of CuOTf with 1 was investigated. Although obtaining the corresponding NHC•CuX species failed, the corresponding NHC•AuCl complex 11 could be synthesized by allowing 1 to react with AuCl•SMe2.

Download Full-text

(±)-trans-1,2-Cyclohexanediamine-Based Bis(NHC) Ligand for Cu-Catalyzed Asymmetric Conjugate Addition Reaction

Catalysts ◽

10.3390/catal9090780 ◽

2019 ◽

Vol 9 (9) ◽

pp. 780 ◽

Cited By ~ 1

Author(s):

Azusa Ishibashi ◽

Shun Kamihigashi ◽

Yuuki Iwai ◽

Satoshi Sakaguchi

Keyword(s):

Catalytic System ◽

Amino Alcohol ◽

Addition Reaction ◽

Conjugate Addition ◽

Addition Reactions ◽

Chiral Ligand ◽

Facial Selectivity ◽

Ligand Precursors ◽

Optically Pure

Bis(NHC) ligand precursors, L1, based on trans-1,2-diaminocyclohexane were designed and synthesized. To introduce chirality at the hydroxyamide side arm on the NHC of L1, a chiral β-amino alcohol, such as enantiopure leucinol, was used. Cu-catalyzed asymmetric conjugate addition reactions of cyclic and acyclic enones with Et2Zn were selected to evaluate the performance of L1 as a chiral ligand. For the reaction of cyclic enone, a combination of [bis(trimethylsilyl)acetylene]-(hexafluoroacetylacetonato)copper(I) (Cu(hfacac)(btmsa)) with a (±)-trans-1,2-cyclohexanediamine-based bis(NHC) ligand precursor, (rac; S,S)-L1, which was prepared from (S)-leucinol, was the most effective. Thus, treating 2-cyclohexen-1-one (3) with Et2Zn in the presence of catalytic amounts of Cu(hfacac)(btmsa) and (rac; S,S)-L1 afforded (R)-3-ethylcyclohexanone ((R)-4) with 97% ee. Similarly, use of (rac; R,R)-L1, which was prepared from (R)-leucinol, produced (S)-4 with 97% ee. Conversely, for the asymmetric 1,4-addition reaction of the acyclic enone, optically pure (−)-trans-1,2-cyclohexanediamine-based bis(NHC) ligand precursor, (R,R; S,S)-L1, worked efficiently. For example, 3-nonen-2-one (5) was reacted with Et2Zn using the CuOAc/(R,R; S,S)-L1 catalytic system to afford (R)-4-ethylnonan-2-one ((R)-6) with 90% ee. Furthermore, initially changing the counterion of the Cu precatalyst between an OAc and a ClO4 ligand on the metal reversed the facial selectivity of the approach of the substrates. Thus, the conjugate addition reaction of 5 with Et2Zn using the Cu(ClO4)2/(R,R; S,S)-L1 catalytic system, afforded (S)-6 with 75% ee.

Download Full-text

Mechanistic analysis of an asymmetric palladium-catalyzed conjugate addition of arylboronic acids to β-substituted cyclic enones

Chemical Science ◽

10.1039/c4sc03337j ◽

2015 ◽

Vol 6 (3) ◽

pp. 1917-1922 ◽

Cited By ~ 17

Author(s):

Cornelia L. Boeser ◽

Jeffrey C. Holder ◽

Buck L. H. Taylor ◽

K. N. Houk ◽

Brian M. Stoltz ◽

...

Keyword(s):

Mass Spectrometry ◽

Addition Reaction ◽

Desorption Electrospray Ionization ◽

Conjugate Addition ◽

Arylboronic Acids ◽

Mechanistic Insight ◽

Mechanistic Analysis ◽

Cyclic Enones ◽

Palladium Catalyzed ◽

Insight Into

Mechanistic insight into a Pd-catalyzed conjugate addition reaction was gained using desorption electrospray ionization coupled to mass spectrometry.

Download Full-text

Inversions in asymmetric conjugate addition reaction of cyclic enones catalyzed by the Cu/NHC-AgX system: Factors affecting the stereoselective formation of both enantiomers

Journal of Organometallic Chemistry ◽

10.1016/j.jorganchem.2017.07.025 ◽

2017 ◽

Vol 846 ◽

pp. 407-416 ◽

Cited By ~ 4

Author(s):

Yuki Nakano ◽

Satoshi Sakaguchi

Keyword(s):

Addition Reaction ◽

Conjugate Addition ◽

Factors Affecting ◽

Cyclic Enones ◽

System Factors

Download Full-text

Total synthesis of clavosolide A via tandem allylic oxidation/oxa-conjugate addition reaction

Tetrahedron Letters ◽

10.1016/j.tetlet.2014.11.135 ◽

2015 ◽

Vol 56 (23) ◽

pp. 3120-3122 ◽

Cited By ~ 10

Author(s):

Joseph B. Baker ◽

Hyoungsu Kim ◽

Jiyong Hong

Keyword(s):

Total Synthesis ◽

Addition Reaction ◽

Conjugate Addition ◽

Allylic Oxidation

Download Full-text

Copper-catalyzed 1,6-conjugate addition of para-quinone methides with diborylmethane

Organic Chemistry Frontiers ◽

10.1039/d1qo00632k ◽

2021 ◽

Author(s):

Xin Li ◽

Guoliang Gao ◽

Songtao He ◽

Qiuling Song

Keyword(s):

Catalytic System ◽

Conjugate Addition ◽

Quinone Methides ◽

High Yields

Presented herein is the first 1,6-conjugate addition of diborylmethane, which is promoted by a simple and inexpensive copper catalytic system. This method features high yields, good selectivities and broad functional...

Download Full-text