Asymmetric Functionalization of C-H Bonds: Volume 25 (Catalysis Series) - Hardcover

Hardcover

ISBN 10: 1782621024 ISBN 13: 9781782621027

Publisher: Royal Society of Chemistry, 2015

Synopsis

Written by a leading expert, this book provides the first comprehensive review of the rapidly developing field of asymmetric C-H direct functionalization reactions.

About this title

About the Author

Shu-Li You is Professor of Chemistry at the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, China. His research interests mainly focus on enantioselective direct C-H bond functionalization and catalytic asymmetric dearomatization (CADA) reaction. Professor You has received numerous awards and is a member of the Advisory Board for several journals, including Chemical Society Reviews, Chemical Communications, Organic & Biomolecular Chemistry, and ACS Catalysis.

From the Back Cover

Asymmetric C-H direct functionalization reactions are one of the most active and fascinating areas of research in organic chemistry due to their significance in the construction of molecular complexity without pre-activation, and the step economy and atom economy features in potential synthetic application. Distinguishing the reactivity among numerous C-H bonds in one single molecule represents one of the most challenging issues in organic synthesis and requires precise reaction design. As such, this field is now receiving increasing attention from researchers.

This book provides the first comprehensive review of this field, summarizing the origin, mechanism, scope and applications of the asymmetric C-H bond functionalization reaction. It covers organocatalytic reactions and transition-metal-catalyzed reactions, as well as asymmetric C-H functionalization reactions not described in other books.

Written by a leading expert in this field, the book is ideal for postgraduates and researchers working in organic synthesis, catalysis, and organometallic chemistry.

From the Inside Flap

Asymmetric C-H direct functionalization reactions are one of the most active and fascinating areas of research in organic chemistry due to their significance in the construction of molecular complexity without pre-activation, and the step economy and atom economy features in potential synthetic application. Distinguishing the reactivity among numerous C H bonds in one single molecule represents one of the most challenging issues in organic synthesis and requires precise reaction design. As such, this field is now receiving increasing attention from researchers.

This book provides the first comprehensive review of this field, summarizing the origin, mechanism, scope and applications of the asymmetric C-H bond functionalization reaction. It covers organocatalytic reactions and transition-metal-catalyzed reactions, as well as asymmetric C-H functionalization reactions not described in other books.

Written by a leading expert in this field, the book is ideal for postgraduates and researchers working in organic synthesis, catalysis, and organometallic chemistry.

Excerpt. © Reprinted by permission. All rights reserved.

Asymmetric Functionalization of C-H Bonds

By Shu-Li You

The Royal Society of Chemistry

Copyright © 2015 The Royal Society of Chemistry
All rights reserved.

ISBN: 978-1-78262-102-7

Contents

Chapter 1 Asymmetric C — H Bond Insertion Reactions Wen-Ting Wu, Ze-Peng Yang, and Shu-Li You, 1, 
Chapter 2 Asymmetric Cross-Dehydrogenative Coupling (CDC) Reactions Shou-Guo Wang and Shu-Li You, 67, 
Chapter 3 Asymmetric Oxidative Biaryl Coupling Reactions Chao Zheng and Shu-Li You, 92, 
Chapter 4 Asymmetric [1,5]-Hydride Transfer Reactions Xiao-Wei Liang, Chao Zheng, and Shu-Li You, 126, 
Chapter 5 Asymmetric Functionalization of C — H Bonds via a Transient Carbon–Metal (C — M) Species De-Wei Gao, Jun Zheng, Ke-Yin Ye, Chao Zheng, and Shu-Li You, 141, 
Chapter 6 Asymmetric Friedel–Crafts Alkylation Reactions Qiang Kang and Shu-Li You, 214, 
Chapter 7 N-Heterocyclic Carbene-Catalyzed Asymmetric Functionalization of Aldehyde C — H Bonds Yi Li and Shu-Li You, 283, 
Chapter 8 Asymmetric Hydroacylation Reactions Qing-Long Xu and Shu-Li You, 358, 
Chapter 9 Asymmetric Hydrovinylation Reactions Qing-Long Xu and Shu-Li You, 384, 
Subject Index, 405, 

CHAPTER 1

Asymmetric C — H Bond Insertion Reactions

WEN-TING WU, ZE-PENG YANG, AND SHU-LI YOU

1.1 C — H Bond Insertion by Metal Carbenoids

1.1.1 Introduction

It has been recognized for over 70 years that C — H bond functionalization can be realized through carbene insertion reactions. In recent years, many outstanding works including asymmetric reactions have appeared in this area.

Considering metal carbenoid-induced C — H bond insertions, there exists a general pattern, as shown in Scheme 1.1. The catalytic cycle is initiated by a metal complex via the decomposition of diverse carbene precursors (such as diazo compounds) to deliver a transient metal carbenoid intermediate in situ. Subsequently, the highly reactive metal carbenoid intermediate inserts into the C — H bond to afford the corresponding product and readily regenerates the metal complex to complete the catalytic cycle. Note that the metal atom is not thought to interact with the C — H bond directly. Moreover, since the transient metal carbenoid intermediate is highly reactive, the reaction conditions are typically mild and pH neutral, which renders this method compatible with a range of functional groups, like halides, triflates, and boronates.

However, the extraordinary reactivity of the carbenoid intermediates, in general, also makes them open to many possible reaction scenarios. Thus, reactivity control has been the essential need when working towards a synthetically useful methodology. Crucial breakthroughs are beginning to be made for the intramolecular approach and a handful of reviews have summarized the progresses on this topic. For intermolecular reactions, reactivity control is more challenging. Besides the intrinsic selectivity of diverse substrates, the key to solving this problem is being able to rely on the metal carbene precursors which, in general, determine the reactivity of the generated metal carbenoid intermediates. Along with the involvement of carbene precursors, especially the diazo compounds, the reactivity of metal carbenoid intermediates can be tunable, and thus an intermolecular approach can be achieved. According to the characteristics of the substituents on the carbene precursors, they can be classified into three major groups: acceptor carbenoid, acceptor/acceptor carbenoid, and donor/acceptor carbenoid (Figure 1.1). The electrophilic properties of the substituents at the metallo-carbenoid carbon center play a significant role in the reactivity and selectivity of the insertion reaction. Generally, an electron-withdrawing group, typically a carbonyl moiety, causes the carbenoid intermediate to be highly electrophilic and reactive, while an electron-donating group stabilizes the carbenoid intermediate. As far as acceptor carbenoids and acceptor/acceptor carbenoids are concerned, an electron-withdrawing group can both make the carbene precursor too stable to be decomposed by a metal complex and render the carbenoid intermediate highly reactive and susceptible to other competing processes. In that case, it is not so hard to understand they are apt to dimerization or hydride transfer to form zwitterionic intermediates, which can be overcome by intramolecular design. However, the donor/ acceptor carbenoids, as late arrivals to the field of metal carbenoid chemistry, revolutionized the situation dramatically and show great potential in highly selective intermolecular C — H bond functionalization; this is because the donating groups present, such as vinyl and aryl, can stabilize the carbenoid through resonance. Meanwhile, the aryl and vinyl groups also make the diazo precursors stable. In this case, highly active catalysts are required to effectively decompose this type of diazo compounds.

Rh and Cu complexes are commonly employed in metal carbenoid-involved asymmetric C — H bond functionalization while chiral catalysts based on Ir, Ru, and Fe as well as Lewis acids came into this area recently. This section aims to introduce the recent developments in asymmetric C — H bond functionalization achieved by metal carbenoids.

1.1.2 C — H Bond Insertion by Rh Carbenoids

Rh-catalyzed asymmetric C — H bond functionalization via a carbene insertion reaction was extensively documented in the early days, especially the intramolecular reactions. Thanks to enormous efforts from the groups of Davies and Doyle, asymmetric intramolecular C — H bond insertion by Rh carbenoids has become a reliable methodology and has been employed frequently in the total synthesis of complex natural products.

One important advantage of the intermolecular carbene insertion reactions is that simple starting materials can be employed and accordingly there is no need for the construction of complex substrates in advance. However, the intermolecular process requires a delicate balance between electronic and steric effects for metal carbenoids. On the other hand, there are several obstacles to be overcome, including chemo-, regio-, and enantioselectivity. Fortunately, great efforts have been devoted in the past decade and a series of carbene precursors and chiral Rh catalysts have been developed, so satisfactory yields and ee can be obtained in some catalytic systems. Generally, suitable carbene precursors, such as donor/acceptor diazo compounds, could reduce the chance of side product formation due to carbene dimerization. On the other hand, the dirhodium bridge caged within a "lantern" structure is thought to be essential to the success of dirhodium complexes in which two rhodium atoms are surrounded by four ligands in a nominal D4 symmetry. Both computational studies and characterization of dirhodium car-benoid intermediates suggested that the intermediate adopts a Rh — Rh=C framework. In another word, two rhodium atoms are bound to one carbene center, and the bonding scenario obeys the three-center orbital paradigm. As such, metal carbenoids derived from chiral RhII complexes and donor/ acceptor diazo compounds are routinely utilized.

Based on initial findings from the studies on achiral catalysts, chiral RhII complexes which have been developed for enantioselective C — H bond functionalization can be classified into four categories: RhII carboxylates, RhII carboxamidates, RhII phosphates, and ortho-metallated arylphosphine RhII complexes (Figure 1.2). Among various RhII complexes, Rh2 (DOSP)4 has proven to be the most effective and versatile catalyst for an array of reactions with a broad range of substrates. In order to understand the outstanding performance on stereocontrol, detailed research (including computational calculations) has been carried out to construct a prediction model.

Furthermore, competition experiments were conducted utilizing donor/ acceptor carbenoids to provide a picture of the relative reactivities among a series of substrates (Figure 1.3). It showed that regioselectivity of different C — H bonds is a balance between steric and electronic factors. Considering the C — H bond insertion reaction, the most reactive sites are those that can mostly stabilize a build-up of positive charge in the transition state. Therefore, the more nucleophilic site, e.g. tertiary C(sp3) — H bond, allylic C — H bond, or C — H bond α to a heteroatom, is more preferred to undergo insertion for electronic reasons. Meanwhile, if the tertiary C(sp) — H bond is comparatively congested and the RhII complex is sterically hindered, the steric effect becomes a significant issue and the reaction will take place at the less crowded C — H bond. In addition, the size of the substituents on the carbenoid source can also impact the regioselectivity due to the steric cause.

Since the Rh-catalyzed asymmetric carbene insertion reactions are relatively well developed methodologies, here we only discuss selected recent successful intermolecular examples, which are classified according to the type of the C — H bond which is functionalized via carbene insertion.

1.1.2.1 Insertion into Unactivated C(sp3) — H Bonds

The first enantioselective intermolecular C — H bond insertion which could be of practical synthetic application was reported in 1997 by Davies and Hansen (Scheme 1.2). In the presence of a variety of relatively unreactive cycloalkane solvents 2 (compared with C — H bonds at the allylic and benzylic positions, as well as C — H bonds α to a heteroatom), the Rh complex Rh2(S-DOSP)4, a privileged catalyst derived from L-proline, was found capable to catalyze the decomposition of aryldiazoacetates 1, inducing the functionalization of cycloalkanes 3 (Scheme 1.2, eqn (1)). Circumventing chemoselectivity and regioselectivity by substrate design, yields and enantioselectivity can reach up to 96% and 93% ee, respectively, by conducting the reactions under refluxing conditions. Further improvements in enantioselectivity (88-96% ee) without considerable decrease in yield were realized by performing the reaction at 10 °C in degassed solvent. It is noteworthy that the key to the success of this intermolecular process is the unusual reactivity and selectivity of aryl-and vinyl-diazoacetates. These donor/acceptor carbenoids are significantly more stabilized and, accordingly, are more versatile than the more traditional carbenoids derived from acceptor and acceptor/acceptor diazoacetates. While other alkanes (4,6, and 8) were subjected to the reaction conditions, the general trend described before (Figure 1.3) was exemplified vividly. Tertiary C — H bonds are much more activated, which can be supported by the formation of the sole corresponding tertiary C — H sites insertion products 5 and 7 in the reactions of 4 and 6 (Scheme 1.2, eqn (2) and (3)), respectively. While 2-meth-ylpentane 8 bearing a sterically demanding tertiary C — H bond was exposed to the reaction conditions, the tertiary C — H bond insertion product 9 and the secondary C — H bond insertion product 9' were afforded in similar yields (Scheme 1.2, eqn (4)). Based on an array of experiments, this catalytic system was shown for the first time to be outstandingly chemoselective and the reactivity of different C — H bonds was expected to follow the sequence: tertiary = secondary [much greater than] primary C — H bonds.

Intriguingly, the dirhodium(II) catalyst Rh2(S-PTAD)4 can be synthesized via the C — H bond insertion of adamantane 6 by the carbenoid derived from vinyldiazoacetate 10 and Rh2(S-DOSP)4 (Scheme 1.3).

Apart from the utilization of aryl- and vinyl-diazoacetates that can achieve the moderate to high chemo-, regio-, and enantioselectivity in intermolecular asymmetric C — H bond insertion reactions, N-sulfonyl-1,2,3-triazole 11 was found to be able to function as an alternative carbene precursor for diverse transformations (Scheme 1.4). One advantage for using the N-sulfonyl-1,2,3-triazole is that it could be easily prepared by the CuI-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, and in some cases, delicately designed reactions can be conducted in a one-pot procedure starting from alkynes and sulfonyl azides. Moreover, since there exists an inherent equilibrium between diazoimines 11' and closed 1,2,3-triazole 11 which favors the latter, the application of N-sulfonyl-1,2, 3triazole removes the need for special slow addition techniques that are often required to guarantee a low concentration of the highly reactive carbenes and parent diazo compounds in the reaction mixture. Accordingly, side products due to carbene dimerization could be largely compressed. Furthermore, the generated metal-bound imino carbenes 11", which are inaccessible from traditional donor/acceptor carbene chemistry, are synthetically useful intermediates and can perform various transformations, such as cycloaddition, ring expansion, ylide formation, and direct heterocycle synthesis.

In 2011, the Fokin group exploited the asymmetric C — H bond insertion reaction between the azavinyl carbenoids derived from triazoles 11 and Rh2(S-NTTL)4 or Rh2(S-PTAD) and a series of inert alkanes 12 under mild conditions (Scheme 1.5). The direct insertion products were converted into the corresponding β-chiral amines 13via subsequent LiAlH4 reduction in up to 97% ee. With respect to the earlier report (Scheme 1.2), higher regioselectivity (5:1) of 13f was observed, suggesting that the insertion reaction favors tertiary C — H bonds over secondary C — H bonds, which can be ascribed to the lower steric requirement of the sulfonyl imine group compared with the ester group in diazoacetate. It was proposed that the RhII catalyst facilitates the ring-chain isomerization of the triazole and the following diazo decomposition.

1.1.2.2 Insertion into Ally lie C(sp3) — H Bonds

It is well-established that olefins tend to undergo cyclopropanation while exposed to metal carbenoids. Meanwhile, olefins also impact the adjacent C — H bonds and enhance the reactivity towards C — H bond insertion reaction by metal carbenoids. It was shown that the chemoselectivity between the intermolecular C — H bond insertion vs. cyclopropanation can be tuned by proper choice of diverse metals, ligands, and carbene precursors. Generally, the donor/acceptor carbenoids (aryldiazoacetate and vinyldiazoacetate) are far more prone towards C — H bond insertion than cyclopropanation, which is opposite to acceptor and acceptor/acceptor carbenoids.

At first, various chiral dirhodium complexes were examined. Enantioselectivity was only moderate while cyclohexene 14a was used as a model substrate and DCM as solvent (entries 1-5, Table 1.1). When the reaction was conducted in 2,2-dimethylbutane (DMB) at -50 °C, the C — H bond insertion product could be obtained in 58% yield and 93% ee (entry 6, Table 1.1).Notably, poor diastereoselectivity is typically observed for intermolecular C — H bond insertion of simple alkenes.

Similarly poor diastereoselectivity was also observed in 1-substituted cyclohexenes 14 and acyclic trisubstituted olefin substrates 17 (Tables 1.2 and 1.3). Despite the excellent chemoselectivity and enantioselectivity that Rh2(S-DOSP) carbenoids generally achieved, the diastereoselectivity was unsatisfactory. It is worth mentioning that the reaction occurs preferentially at the sterically less hindered allylic site.

It was proposed that considerable size differentiation between the two potential reaction sites for the C — H bond insertions [e.g. C3 in Table 1.4) would help to improve the diastereoselectivity. Under such a hypothesis, installation of a bulky vinylsilane group at the C1 position becomes a wise choice because it not only provides the desired stereo differentiation but also eliminates cyclopropanation as a side reaction for steric reasons. Indeed, while TBDPS was introduced (Table 1.4, entry 2), good diastereoselectivity could be achieved.

While silyl enol ethers 21 and 23 were subjected to similar reaction conditions (Tables 1.5 and 1.6), the allylic C — H bond could also be functionalized by metal carbenoids to afford silyl-protected 1,5-dicarbonyls 22 and 24 respectively, which can be viewed as an equivalent of an asymmetric Michael reaction. Although the double bond is highly electron-rich and readily undergoes cyclopropanation in the presence of most other metal carbenoids, by using aryldiazoacetates 1 as carbene precursors, cyclic silyl enol ethers 21 were readily transformed into their corresponding allylic C — H bond insertion products 22 (22') in excellent yields, excellent ee and moderate de (Table 1.5). Noticeably, while acyclic silyl enol ethers 23 were subjected to the reaction, excellent diastereoselectivity (>90% de) was obtained, which shows great potential in synthetic applications (Table 1.6).

(Continues...)

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Edition details

• Publisher: Royal Society of Chemistry
• Publication date: 2015
• Language: English
• ISBN 10: 1782621024
• ISBN 13: 9781782621027
• Binding: Hardcover
• Number of pages: 432
• Editor: Shu-Li You