Copper(II)-Catalyzed Asymmetric Photoredox Reactions

Subscriber access provided by Kaohsiung Medical University

Article

Copper(II)-Catalyzed Asymmetric Photoredox Reactions: Enantioselective Alkylation of Imines Driven by Visible Light Yanjun Li, Kexu Zhou, Zhaorui Wen, Shi Cao, Xiang Shen, Meng Lei, and Lei Gong J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 16 Oct 2018 Downloaded from http://pubs.acs.org on October 16, 2018

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 32 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Journal of the American Chemical Society

Copper(II)-Catalyzed

Asymmetric

Photoredox

Reactions:

Enantioselective Alkylation of Imines Driven by Visible Light Yanjun Li, Kexu Zhou, Zhaorui Wen, Shi Cao, Xiang Shen, Meng Lei, Lei Gong* Key Laboratory of Chemical Biology of Fujian Province, iChEM, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, China. E-mail: [email protected]

ABSTRACT Asymmetric photoredox catalysis offers exciting opportunities to develop new synthetic approaches to chiral molecules through novel reaction pathways. Employing the first-row transition metal complexes as the chiral photoredox catalysts remains however a formidable challenge although these complexes are economic, environmentally friendly and often exhibit special reactivities. We report in this paper the development of one class of highly efficient asymmetric/photoredox bifunctional catalysts based on the copper(II) bisoxazoline complexes (CuII-BOX) for the light-induced enantioselective alkylation of imines. The reactions proceed under very mild conditions and without a need for any other photosensitizer. The simple catalytic system and readily tunable chiral ligands enable a significantly high level of

ACS Paragon Plus Environment

Journal of the American Chemical Society 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

enantioselectivity for the formation of chiral amine products bearing a tetrasubstituted carbon stereocenter (36 examples, up to 98% ee). Overall, the CuII-BOX catalysts initiate the radical generation, and also govern the subsequent stereoselective transformations. This strategy utilizing chiral complexes comprised of a first-row transition metal and a flexible chiral ligand as the asymmetric photoredox catalysts provides an effective platform for development of green asymmetric synthetic methods.

INTRODUCTION Visible-light photoredox catalysis has been developed into a powerful tool to construct carbon-carbon or carbon-heteroatom bonds in organic synthesis.1 Through high-energy intermediates such as radicals and radical ions, unique reactions that are unavailable under thermal conditions can be accessed. Significant advances have been achieved in this field by employing ruthenium(II), iridium(III) complexes or organic dyes as photoredox catalysts.2 In contrast, the use of first-row transition metal complexes such as copper species has been much less frequently reported.3–7 Beside the aspects of relatively shorter excited-state lifetimes and weaker visible-light absorption, an inherent drawback of copper complexes as photoredox catalysts is that the low reduction potentials of CuIICuI might impede the closure of a photocatalytic cycle.4 Very recently, an appealing strategy involving lightaccelerated homolysis (CuII-X CuII-Y CuI + Y‧) has been developed to address this


Page 2 of 32

Page 3 of 32 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


problem, and opens up new avenues for copper-based photocatalysis.8 On the other hand, asymmetric catalysis promoted by visible light is emerging as an attractive synthetic strategy for chiral organic molecules. However, achieving a high level of enantioselectivity in the photoredox reactions remains a remarkable challenge.9 In the limited success that has been reported, the solutions typically rely on the dual catalysis involving a ruthenium or iridium-based photocatalyst and a chiral co-catalyst, which often contains one or more precious metals.10 Bifunctional catalysis employing a chiral-atiridium or rhodium complex as both the asymmetric catalyst and photocatalyst has also been developed by Meggers and other groups recently.11,12 Although use of a single chiral complex of a first-row transition metal as the asymmetric photocatalyst would be economically attractive and environmentally friendly, it has been scarcely explored.13–15 An impressive pioneering work by Fu et al. disclosed light-promoted enantioselective CN cross-couplings by a copper(I) catalyst containing a chiral phosphine ligand.13 Even more recently, a nickel(II)-DBFOX-catalyzed enantioselective photoredox reaction of α,βunsaturated carbonyl compounds and α-silylamines was developed in our laboratory.14 These studies revealed that chiral complexes of first-row transition metal exhibit special features and reactivities in photochemical reactions beyond the role as inexpensive alternatives to ruthenium or iridium-based photocatalysts. Therefore, development of new chiral photocatalysts or applications based on the first-row transition metals would be of great value and in high demand. Herein, we disclose the development of one class of copper(II) bisoxazoline



Page 4 of 32

complexes (CuII-BOX) as asymmetric/photoredox bifunctional catalysts in the lightinduced enantioselective alkylation of imines (Scheme 1). Without the need of any other photosensitizer and under very mild conditions, the copper-catalyzed photochemical reactions afforded a range of chiral amine products containing a tetrasubstituted carbon stereocenter with good to excellent enantioselectivities.

N Ar

R1 + COR2

R3

BF3K

HN

Cu(BF4)2/BOX CHCl3, -20 C blue LEDs

R1

R'

R3

Ar

COR2 36 examples up to 98% ee

R'

O

O N

R

N II

R

[Cu ] II

[Cu -BOX]

[CuII-BOX]

Photoredox Catalysis

Asymmetric Catalysis

[CuII-BOX]

R3 [imine-CuII-BOX]

• chiral photoredox catalysts of first-row transition metal • radical pathway providing with high ees

Ar

HN

R1

R3

COR2

• light-active copper(II) catalysts

• broad scope for both cyclic and acyclic imines

Scheme 1. Strategy of using a single CuII-BOX complex as the chiral photoredox bifunctional catalyst.

 RESULTS AND DISCUSSION Initial experiments. In our primary studies on catalyst selection, we found that several chiral copper(II) bisoxazoline complexes (CuII-BOX) exhibited obvious absorption in the visible-light region. In particular, absorption in the range of 400–550 nm, attributed


Page 5 of 32 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


to metal-ligand-charge-transfer (MLCT), was one of the key features required for a visiblelight photocatalyst. In combination with their readily tunable chiral environment, redoxactive metal center and the established photoactivities of their reduced states–copper(I) species,4 we assumed that these chiral copper(II) complexes might be potential candidates for the development of asymmetric photoredox catalysis based on the first-row transition metals. Accordingly, we developed a model catalytic system using in-situ generated copper(II) bisoxazoline complexes as the catalyst, benzyl trifluoroborate 2a as the radical precursor, and an α-carbonyl imine 1a as the coupling partner.16 The α-carbonyl adjacent to the C=N bond of the imine substrate was thought to be able to act as a directing group for the asymmetric induction.17 Such a photochemical reaction would lead to the development of an inexpensive method for radical-based enantioselective alkylation of imines under mild and convenient conditions.18 In an initial experiment, the mixture of substrate 1a, 2a, premixed copper salt Cu(BF4)2∙H2O (10 mol%) and ligand L1 (11 mol%) in chloroform was stirred at 25 °C in argon under irradiation with a 24 W blue LEDs lamp. The desired product (3a) was produced in quantitative yield and with 74% ee (Table 1, entry 1). In the absence of the blue LEDs lamp, stirring in the dark at room temperature (entry 2) or 80 °C (entry 3), removing the ligand (entry 4) or the copper salt (entry 5), the reaction failed to proceed. Addition of another photosensitizer such as [Ru(bpy)3](PF6)2 dramatically accelerated the reaction (2 h, 100% conversion, entries 6–7), implying a light-induced pathway. Water was



Page 6 of 32

well-tolerated in the system (entry 8) while protic additive such as methanol led to the lower reaction rate and slightly reduced enantioselectivity (entry 9).

Table 1. Initial experiments and optimization of reaction conditionsa O

S

O BF3K

N

+ Cl CO2Et

1a

O

R1

1 2 3 4 5 6d

metal salt

NH

CO2Et 3a

Ph Ph

R1

ligand T (°C)

Cu(BF4)2∙H2O L1 Cu(BF4)2∙H2O L1 Cu(BF4)2∙H2O L1 Cu(BF4)2∙H2O none none L1 Cu(BF4)2∙H2O L1

25 25 80 25 25 25

Ph

N

N

N

L8

O

O

O

O

L1: R1 = Ph, R2 = R3 = Me L2: R1 = iPr, R2 = R3 = Me L3: R1 = Bn, R2 = R3 = Me O L4: R1 = Ph, R2 = Me, R3 = Bn N L5: R1 = Ph, R2 = R3 = Bn L6: R1 = Ph, R2 = R3 = CH2Ph(4-tBu) Ph L7: R1 = Ph, R2 = R3 = CH2Ph[4-(1-Ad)]

entry

Cl

O

Bn Bn

R2 R3 N

[M] / L*

S

argon light source

2a

O

O

N

Ph

N L9

O

N

PPh2 PPh2

N Ph

L10

L11

light source

t (h)

blue LEDs none none blue LEDs blue LEDs blue LEDs

6 12 12 12 12 2


conv. (%)b quant. 0 0 0 0 quant.

ee (%)c 74 n.a. n.a. n.a. n.a. 73

Page 7 of 32 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


7d none none e 8 Cu(BF4)2∙H2O L1 f 9 Cu(BF4)2∙H2O L1 10 Cu(OTf)2 L1 11 Cu(MeCN)4BF4 L1 12 Ni(OTf)2 L1 13 Fe(OTf)3 L1 14 Cu(BF4)2∙H2O L2 15 Cu(BF4)2∙H2O L3 16 Cu(BF4)2∙H2O L4 17 Cu(BF4)2∙H2O L5 18 Cu(BF4)2∙H2O L6 19 Cu(BF4)2∙H2O L7 20 Cu(BF4)2∙H2O L8 21 Cu(BF4)2∙H2O L9 22 Cu(BF4)2∙H2O L10 23 Cu(BF4)2∙H2O L11 24 Cu(BF4)2∙H2O L7 25 Cu(BF4)2∙H2O L7 26g Cu(BF4)2∙H2O L7 27g Cu(BF4)2∙H2O L7 28g Cu(BF4)2∙H2O L7 29g Cu(BF4)2∙H2O L7 aReaction

25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 0 -20 -40

blue LEDs blue LEDs blue LEDs blue LEDs blue LEDs blue LEDs blue LEDs blue LEDs blue LEDs blue LEDs blue LEDs blue LEDs blue LEDs blue LEDs blue LEDs blue LEDs blue LEDs red LEDs UV lamps blue LEDs blue LEDs blue LEDs blue LEDs

12 6 15 6 6 21 21 6 6 6 6 6 6 6 6 6 6 6 6 3 3 12 21

22 quant. 93 92 quant. 0 0

Copper(II)-Catalyzed Asymmetric Photoredox Reactions

Recommend Documents