Astruc D. - Modern arene chemistry (2002)(en)

13.5 CT Complexes as Critical Intermediates in Donor/Acceptor Reactions of Arenes 473

turally related [65] nitrosonium (NOþ) cation [66], let us consider the corresponding reaction profiles constructed in the framework of the ET paradigm. While the reduction potentials of NOþ and NO2þ are comparable in di erent solvents [67], there is a large di erence between NOþ and NO2þ in terms of the magnitudes of their reorganization energies, which di er by a factor of 2, i.e.: lNO2 ¼ 140 kcal mol 1 and lNO ¼ 69 kcal mol 1, largely as a result of the requisite bending of ONO attendant upon the reduction of the almost linear (triatomic) cation [67]. In order to follow through with the comparison to NOþ, let us consider the corresponding ET process, viz.:

Scheme 25

Since the temporal course of ET cannot readily be followed owing to the high reactivity of NO2þ, we rely on the comparison of the reorganization energy to draw some broad estimates of the electron coupling element for the pre-equilibrium intermediate in Scheme 25. If we take HDA to be the same as that for NOþ as a first approximation, the ET potential-energy profile will consist of a double potential minimum consisting of a separate precursor (PC) p- complex [ArH, NO2þ] and successor (SC) complex [ArHþ , NO2 ], both with progressively shallower minima (and higher barriers separating them) as the electronic coupling element HDA decreases. In the limit with HDA A0, a single barrier separates the non-interacting reactant state fArH þ NO2þg and the final state fArHþ þ NO2 g. In other words, as a result of the large lNO2, electron transfer with NO2þ cannot progress via a single pre-equilibrium p- complex like that with NOþ, and the typical cross-section of the potential energy surface includes a pair of pre-equilibrium p-intermediates (PC and SC). As a consequence of the di erent potential-energy profiles, with a double minimum for NO2þ and a single minimum for NOþ (Chart 4), the rate of electron transfer to NO2þ is significantly faster than that to NOþ, despite the larger magnitude of lNO2 relative to lNO, since Chart 8 shows that the activation energy for overall electron transfer is simply given as DG0ET ¼ DG ET. The pre-equilibrium formation of CT complexes is common to both aromatic nitrosation and nitration, which are known to occur via the active electrophilic species NOþ and NO2þ, respectively [68]. As such, the interconversion of the p-complex to the s-adduct (like that for bromination) represents the critical activation step, i.e.:

Chart 8

474 13 Charge-Transfer Effects on Arene Structure and Reactivity

Scheme 26

The least-motion study of such (direct or one-step) transformations cannot readily account for the fact that NO2þ moiety must overcome the sizable (reorganization) penalty for ONO bending. Such a significant reorganizational obstacle is conceptually circumvented by decoupling the step involving reorganization from the step leading to the s-adduct in Scheme 26. Indeed, ET activation as presented in Charts 4 and 8 for NOþ and NO2þ, respectively, satisfies the two-step criterion, since reorganization is implicit in ET and it is separate from s-adduct formation.

As applied to aromatic nitrosation, the activation process is:

Scheme 27

where the overall activation barrier (DG0) is evaluated from Eq. (14) [69]. Thus, slow electron transfer, coupled with the subsequent slow deprotonation of the s-adduct [70], is responsible for aromatic nitrosations, which are by and large limited to only the most active (electronrich) arene donors [71].

The corresponding two-step activation of aromatic nitration involves an additional intermediate, the successor complex (SC) ¼ [ArHþ , NO2 ], which largely takes on the burden of the NO2þ reorganization in the separate ET transformation of the precursor complex (PC) ¼ [ArH, NO2þ]. As such, the subsequent (spontaneous) collapse of SC directly to the s- adduct considerably facilitates the ET pathway for nitration [72] since it entirely by-passes the slow (energy-intensive) step leading from the SC or [ArHþ , NO2 ] to the separated (noninteracting) ion-radical pairs fArHþ þ NO2 g, i.e.:

Scheme 28

The activation barrier for such a direct collapse of the ion-radical pair is substantially less than DGET (see pathway P1 in Chart 7) and leads to very fast nitration rates [73]. (The latter underscores the caveat that the viability of ET mechanisms cannot be pre-judged [67] solely by the value of DGET ).

Formation of the Wheland intermediate from the ion-radical pair as the critical reactive intermediate is common to both nitration and nitrosation processes. The nitrosoarenes (unlike their nitro counterparts) are excellent electron donors, as judged by their low Eox o as

References 475

compared to the parent arene [74]. As a result, nitrosoarenes are also better Brønsted bases [75] than the corresponding nitro derivatives, and this marked distinction readily accounts for the large di erentiation in the deprotonation rates of their respective conjugate acids (i.e. Wheland intermediates). In the case of aromatic nitration with NO2þ, deprotonation is fast and occurs with no kinetic (deuterium) isotope e ect. The slower rates of formation of the radical pair leading to Wheland intermediates, together with slower rate of the deprotonation of these intermediates, results in a dramatic di erence between the rate of nitration and that of nitrosation.

13.6

Concluding Summary

Arenes are electron donors by virtue of the ease with which they form intermolecular complexes with a variety of electrophiles, cations, acids, and oxidants that are all su ciently electron-poor to be generally classified as electron acceptors (A). Three structural features are common to all arene complexes that have been isolated and subjected to X-ray crystallo-

graphic analysis, namely: (i) their p-structure, either as the axially symmetric

or

the asymmetric

forms, (ii) their inner-sphere character, such that the separation

of the acceptor (A) from the aromatic plane is less than the sum of their van der Waals radii, and (iii) the significant enlargement of the aromatic chromophore with average bond distances between ring carbons that can approach those extant in the corresponding arene cation radicals.

Charge transfer as depicted by Mulliken provides a single unifying basis for predicting arene reactivity based on the spectral, structural (both molecular and electronic), and thermodynamic properties of their intermolecular complexes, from stable organometallic derivatives to non-bonded collision complexes with very short lifetimes.

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478 13 Charge-Transfer Effects on Arene Structure and Reactivity

E. Gabe, F. Lee, A. Piotrwski, Can. J.

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61S. V. Rosokha, J. K. Kochi, J. Org. Chem.

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69The stepwise activation process for DGET is:

Note that, in this treatment, the energy of the pair of radicals fArHþ þ NO g is more or less equivalent to that of the s- adduct, as previously established experimentally by their simultaneous observation by time-resolved spectroscopy. See S. M. Hubig, J. K. Kochi, J. Am. Chem. Soc. 2000, 122, 8279.

70To account for the sizable deuterium kinetic isotope e ect in aromatic

nitrosation, see: E. Bosch, R. Rathore, J. K. Kochi, J. Org. Chem. 1994, 59, 2529–2536.

71Electron-rich arenes yield the most stable cation radicals, as indicated by their enhanced values of KET. Thus, the enhanced yields of arene cation radicals from electron-rich arenes will correlate with faster nitrosation rates.

72a) Independent time-resolved (ps) spectroscopic studies have established the facile (homolytic) coupling of the arene cation radical (ArHþ) with NO2 to form the s-adduct, the second-order process of which occurs at di usion-controlled rates. See: E. K. Kim, T. M. Bockman, J. K. Kochi, J. Am. Chem. Soc. 1993, 115, 3091;

b)It is important to emphasize that the electron-transfer mechanism for aromatic nitration in Scheme 28 merely di ers quantitatively from that originally proposed by Perrin [72c], in that the successor

complex [ArHþ, NO2 ] and not a pair of radicals fArHþ þ NO g is considered to be the reactive intermediate. For a quantitative delineation of this (kinetic) distinction, see: (c) C. L. Perrin, J. Am. Chem. Soc. 1977, 99, 5516.

73It is important to emphasize that the chemical behavior of the successor complex [ArHþ, NO2 ] in Class II systems is more like that of the pair of free radicals

fArHþ and NO2 g. The extent to which the NO2 moiety in the successor complex is already bent (i.e. substantially) will further facilitate collapse to the s-adduct. In this regard, the successor complex in Class II systems is very di erent from the

Class III pre-equilibrium complex [ArH, NO]þ, which exhibits ion-radical behavior only upon separation to the free fArHþ and NO g species [61].

74E. Bosch, J. K. Kochi, J. Org. Chem. 1994,

59, 5573.

75R. G. Pearson, in Nucleophilicity (Eds.: J. M. Harris, S. P. McManus), Adv. Chem. Ser. 215, American Chemical Society, Washington DC, 1987.

479

14

Oxidative Aryl-Coupling Reactions in Synthesis

Guillaume Lessene and Ken S. Feldman

Abstract

The oxidant-mediated coupling of electron-rich arene rings has served over several decades as a valuable procedure to access biaryl units. The complex mixtures of isomers that often plagued the earliest studies have gradually given way to synthetically useful product distributions upon application of more selective coupling protocols. Continual advances in the nature of the oxidant (and its attendant ligands) and more precisely defined reaction conditions have led to increasing levels of control upon CaC bond formation. Chemoselective (CaC vs. CaO bond formation with phenols; suppression of product oxidation), regioselective (o-o0, vs. o-p0 vs. p-p0 CaC bond formation), and, more recently, stereoselective (atropisomer-selective) biaryl bond formation can now be achieved in many well-defined systems. A survey of the more recent advances in these areas is presented.

14.1

Introduction

The biaryl moiety is a prominent structural feature in numerous naturally occurring and biologically active molecules. Strategies to achieve e cient syntheses of these essential structures have therefore been the focal point of much attention in recent years. Among all of the available methods, the venerable oxidative coupling of arenes, and, in particular, of phenols, is of special interest in view of the presumed reliance on this chemistry in the biosynthesis of these types of compounds. Therefore, biomimetic syntheses of biaryl fragments by oxidative coupling of diaryl precursors have been the goal of many studies within this field.

Considering the broad variety of substrates that take part in oxidative arylic coupling, the challenge has always been, and still is, achieving selectivity upon CaC bond formation. Whereas evolutionary pressures can be brought to bear in order to engineer an enzyme catalyst to promote formation of a single product, the in vitro mimicry of this reaction’s specificity must address several issues, including over-oxidation, chemoselectivity, regioselectivity, and, finally, stereoselectivity. By examining both the history of this chemistry and the current state of the art of oxidative coupling reactions, some appreciation of how these di erent problems have been overcome can be realized.

Modern Arene Chemistry. Edited by Didier Astruc

Copyright 8 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30489-4

480 14 Oxidative Aryl-Coupling Reactions in Synthesis

The oxidative coupling of phenols has been known since the 19th century, but seminal studies carried out by Pummerer [1–8], who identified a phenolic radical as an intermediate of the reaction, initiated the modern age of mechanistic understanding in this area. It was then demonstrated that this radical mechanism also occurs in Nature, to produce complex biaryl-containing phenolics [9, 10].

Initially, the potent oxidizing agent potassium ferricyanide was used in this chemistry [11]. Anodic oxidation was examined concurrently as a synthetic tool [12] and later as an analytical method for demonstrating the existence of the phenoxyl radical [13, 14] in the course of mechanistic studies on these couplings. In addition to the earlier methods, phenolic oxidations using dioxygen, halogens, enzymes, etc., also were reported sporadically. The introduction of vanadium complexes (VOCl3 [15], VOF3 [16]) and later of thallium [17] and lead reagents [18] o ered more reliable reactions and partially solved problems such as over-oxidation and regioselectivity of CaC bond formation between aryl rings. With the use of these reagents, and also by electrochemical methods, it also became possible to utilize phenol ethers in coupling reactions.

More recently, a new class of non-metallic oxidation reagents has been reported – the hypervalent iodine complexes [19]. Phenyliodine(III) diacetate (PIDA) and phenyliodine(III) bis(trifluoroacetate) (PIFA) have proven to be very e cient reagents that give rise to higher regioselectivity than other oxidants in some reactions and, more importantly, o er a mild and non-toxic alternative to the heavy metals.

A broad range of biaryl structures, as is often encountered in various classes of naturally occurring compounds, such as alkaloids, lignans, and tannins, can be prepared by oxidative arylic coupling. Oxidative couplings have also been used to build non-natural skeletons, such as the binaphthol derivatives that play an important role in asymmetric synthesis.

A large number of reviews have previously been published in the field of oxidative coupling reactions [11, 20–26]. In this chapter, current thinking on the di erent mechanisms involved in these types of reactions and the most recent developments in this field will be presented. Although the period of time between the earliest attempts, which resulted in nonselective and low-yielding reactions, and the more advanced approaches leading to mild, efficient, and regioselective AraAr bond formation is quite significant (almost a century), most of the progress has been made only over the past two decades. The last few years have seen a real acceleration in methodological advances, especially in the area of stereoselection upon biaryl bond formation. Therefore, an important part of this chapter is devoted to the issues of atropisomerism and stereoselection that arise during the formation of a complex biaryl system. In addition, the latest work on catalytic systems that promote enantioselective biaryl coupling reactions is highlighted.

14.2

Mechanistic Overview

The oxidative coupling of two aryl units 1 leads formally to a loss of two electrons and two protons (Scheme 1).

Two di erent mechanisms are conceivable for the electron-transfer portion of this transformation: two ‘‘single-electron’’ transfers or one ‘‘two-electron’’ transfer. Moreover, when dealing with phenolic compounds, the pH (protonation state of the phenol) can also influ-

14.2 Mechanistic Overview 481

Scheme 1. The essentials of biaryl formation by oxidative coupling of arenes.

ence the mechanistic pathway taken. A mechanistic matrix (Scheme 2) underscores the different states of oxidation/protonation of a phenol unit, and illustrates how each component can be involved in the reaction. Identifying the initial oxidized aryl unit is important for understanding the coupling reaction.

Scheme 2. A comprehensive schematic for phenol oxidation/deprotonation.

The first and most simplistic way of considering the coupling reaction was presented by Pummerer, who described the coupling of two radicals 7. The mesomeric structures 7a and 7b of this intermediate help to rationalize the poor selectivity achieved when reagents such as potassium ferricyanide are used. The calculated electron density within 7 shows that coupling can occur via the oxygen atom (products 9 and 10) as well as at the ortho and para positions of the aryl ring (products 11–13, Scheme 3). However, substituents on the aromatic ring influence the choice of coupling position through steric and electronic e ects. Thus, judicious selection/placement of substituents can limit the number of isomers obtained.

Scheme 3. Phenoxy radical coupling possibilities.

482 14 Oxidative Aryl-Coupling Reactions in Synthesis

Generally, when two di erent aryl units are involved in a coupling reaction, the oxidation potentials of the two units will be di erent. In another mechanistic variant, the more easily oxidized phenol 14 can react with the other unperturbed aromatic unit 15 to furnish a ‘‘biaryl’’ radical 16, which then oxidizes further, deprotonates, and finally tautomerizes to give the product biaryl (Scheme 4).

Scheme 4. Coupling of a phenoxy radical with an intact phenol.

Oxidants that operate according to this one-electron oxidation mechanism include potassium ferricyanide in alkaline solution, cobalt, copper complexes with dioxygen, and some enzymes.

More involved studies of the oxidation of plant phenols [27], as well as the introduction of thallium and hypervalent iodine complexes and the use of electrochemical methods, have emphasized the importance of another intermediate involved in oxidative coupling reactions, namely the phenoxonium ion 8 [28–30]. Due to its ionic nature, reaction through an oxonium ion can improve the regioselectivity of bond formation and lead to fewer unwanted products (for example, no coupling via the oxygen atom). The coupling reaction can then be viewed as an electrophilic aromatic substitution between 17 and a nucleophilic aromatic unit 15 (Scheme 5).

Scheme 5. Phenoxonium ion coupling chemistry.

Vanadium, thallium, and lead complexes might involve 17 or a metal-bound equivalent 21 as an intermediate, although mechanistic details remain obscure for most metal-based systems (Scheme 6a). Phenol derivatives bearing a leaving group on the alcohol, e.g. 22, may also follow this mechanistic pathway involving a phenoxonium ion or an equivalent thereof. Hypervalent iodine reagents are commonly used in this context, as they have the advantage of being very e cient, mild, and non-toxic (Scheme 6b) [31].