Perspective Cite This: ACS Catal. 2018, 8, 5466−5484
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Catalytic Asymmetric Oxidative Enamine Transformations Lihui Zhu,†,‡,⊥ Dehong Wang,†,‡,⊥ Zongbin Jia,†,‡ Qifeng Lin,†,‡ Mouxin Huang,§ and Sanzhong Luo*,†,‡,§,∥ †
Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, People’s Republic of China ‡ University of Chinese Academy of Sciences, Beijing 100490, People’s Republic of China § Center of Basic Molecular Science (CBMS), Department of Chemistry, Tsinghua University, Beijing 100084, People’s Republic of China ∥ Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, People’s Republic of China ABSTRACT: Enamine catalysis is a prevalent strategy for the functionalization of aldehydes/ketones with electrophiles. Recently, the advent and development of oxidative enamine catalysis have allowed for the coupling of enamines with readily available nucleophiles under oxidative conditions, significantly expanding the domain of typical enamine catalysis. In this perspective, we summarize the recent advances in asymmetric oxidative enamine catalysis. On the basis of the oxidative strategy, these could be classified as (1) oxidation of nucleophile, (2) oxidation of enamine via single-electron transfer (SOMO catalysis), and (3) oxidation of enamine to α,β-unsaturated iminium ion, i.e. oxidative iminium catalysis. These strategies have enabled efficient oxidative functionalizations of aldehydes/ketones with various O-, N-, and C-centered nucleophiles in a highly stereocontrolled manner. KEYWORDS: organocatalysis, aminocatalysis, enamine transformation, oxidative enamine catalysis, nucleophile
1. INTRODUCTION Within the realm of organic synthesis, the carbonyl moiety represents one of the most prevalent functional groups that has been widely used in synthetic transformations.1 Enantioselective methodologies along this line undergo constant rebirth, echoing each of the advances in asymmetric catalysis. Over the last two decades, enamine catalysis has evolved into an enabling and powerful strategy for enantioselective transformations of aldehydes and ketones. The typical enamine catalytic process involves the coupling of a nucleophilic enamine intermediate with an electrophile for C−C/C−X bond formations (Scheme 1).2 Beyond its well-defined nucleophilic feature, enamine is also rich in redox properties and could be readily oxidized to an electron-deficient structure upon a single-electron transfer or electron/proton transfer process.3,4 Recently, there have been rapid advances in the exploration of oxidative strategies in enamine catalysis (Scheme 1). The resulting oxidative enamine catalysis enables the coupling with nucleophiles under properly balanced oxidative conditions, thus significantly expanding the scope of typical enamine catalysis. One easily conceived oxidative strategy is to in situ oxidize the nucleophile into an electrophile, which then participates in a typical enamine cycle to generate C−C or C−X bonds (Scheme 1, I). The other two oxidative strategies involve the oxidation of enamine itself into electrophilic species. Upon a single-electrontransfer (SET) process, enamines could be oxidized into © XXXX American Chemical Society
electrophilic radical cation species, which are able to couple with nucleophiles, generating α-functionalized products (Scheme 1, II). Apart from this SET process, enamine intermediates could also undergo a dehydrogenative process to generate iminium ion intermediates, followed by a Michael-type nucleophilic attack. In this process, a β-substituted product was generated (Scheme 1, III). In this perspective, we summarize recent advances in asymmetric oxidative enamine catalysis, categorized by the three different oxidative strategies.
2. OXIDATION OF NUCLEOPHILES In this section, we mainly discuss a well-established classic enamine catalysis cycle merged with the oxidation of nucleophiles. The primary concern of this oxidative coupling is the oxidative tolerability of the redox-labile enamine species and amine catalyst. 2.1. Oxidative Dearomatization. In 2008, Gaunt reported an enamine-based oxidative dearomatization process in which in situ generated quinone could react as a Michael acceptor with enamine, forming highly functionalized chiral cyclohexadieneone in moderate yield and excellent enantioselectivity (Scheme 2).5 PhI(OAc)2 was identified to be a viable oxidant that enabled Received: March 30, 2018 Revised: May 2, 2018 Published: May 4, 2018 5466
DOI: 10.1021/acscatal.8b01263 ACS Catal. 2018, 8, 5466−5484
Perspective
ACS Catalysis Scheme 1. Working Modes for Asymmetric Oxidative Enamine Catalysis
reaction with dienal and hydroquinone under PhI(OAc)2 oxidation. Through a combination of a Diels−Alder reaction and conjugate addition, tricyclic compound 5a could be successfully generated in moderate yield and high enantioselectivity.8 Subsequently, they further extended the reaction to synthesize polycyclic compounds 5b by introducing 1,4naphthoquinone as substrate (Scheme 5).9 2.2. α-C−H Oxidation of Amines and Ethers. Crossdehydrogenative coupling (CDC) with C(sp3)−H bond, pioneered by the Murahashi group and the Li group, has recently been established as a versatile C−C/C−X bond formation strategy under oxidative conditions.10 Various catalytic approaches have been explored in order to achieve enantioselective CDC reactions, and asymmetric enamine catalysis turns out to be a powerful strategy in CDC reactions with aldehydes and ketones. Klussmann reported first oxidative coupling of tertiary amines with unactivated ketones by enamine catalysis in 2009.11a This transformation received moderate to excellent yield via a synergistic coupling of the in situ generated enamine and iminium ion intermediate derived from acetone and tertiary amine, respectively. However, the reaction afforded a poor yield and
