DOtz reaction

The coupling reaction of an a ,/3-unsaturated chromium carbene complex, e.g. 1, and an alkyne 2, through coordination to the chromium center, is called the Dotz reaction. The initial product is the chromium tricarbonyl complex of a hydroquinone derivative 3, which can easily be converted to a free hydroquinone or quinone. 

The synthetic value of the Dotz reaction has for example been demonstrated by the synthesis of vitamin Ki(20) 10 (simplified structure). This natural product has been prepared synthetically from the chromium carbene complex 8 and the alkyne 9 in two steps the second step being the oxidative decomplexation to yield the free product 10 ... 

Because of the strongly electron-withdrawing character of the Cr(CO)5 unit, the reaction with alkynes to hydroquinone and phenol derivatives [35-37] (Dotz reaction) is possible according to Scheme 6 (see also Chap. 4 Chromium -templated Benzannulation Reactions ). 

In 1986 Yamashida et al. found that the reaction of the (morpholino)phenyl-carbene complex 46 with symmetric alkynes 47 gave the morpholinylindene derivatives 48 and 49, as well as the indanones 50 derived from the latter by hydrolysis, in excellent yields (Scheme 9) [54]. This contrasts with the behavior of the corresponding (methoxy)phenylcarbene complex, which solely undergoes the Dotz reaction [55]. This transformation of the amino-substituted complex 46 apparently does not involve a CO insertion, which is an important feature of the Dotz benzannelation. 

The formation of the tricarbonylchromium-complexed fulvene 81 from the 3-dimethylamino-3-(2 -trimethylsilyloxy-2 -propyl)propenylidene complex 80 and 1-pentyne also constitutes a formal [3+2] cycloaddition, although the mechanism is still obscure (Scheme 17) [76]. The rf-complex 81 must arise after an initial alkyne insertion, followed by cyclization, 1,2-shift of the dimethylamino group, and subsequent elimination of the trimethylsilyloxy moiety. Particularly conspicuous here are the alkyne insertion with opposite regioselectivity as compared to that in the Dotz reaction, and the migration of the dimethylamino functionality, which must occur by an intra- or intermo-lecular process. The mode of formation of the cyclopenta[Z ]pyran by-product 82 will be discussed in the next section. 

Dotz reaction, since both an alkyne and CO are inserted. However, the additional double bond present in the starting complex participates in the subsequent electrocyclic ring closure, giving rise to eight-membered carbocycles. 

Aryl- and alkenylcarbene complexes are known to react with alkynes through a [3C+2S+1C0] cycloaddition reaction to produce benzannulated compounds. This reaction, known as the Dotz reaction , is widely reviewed in Chap. Chromium-Templated Benzannulation Reactions , p. 123 of this book. However, simple alkyl-substituted carbene complexes react with excess of an alkyne (or with diynes) to produce a different benzannulated product which incorporates in its structure two molecules of the alkyne, a carbon monoxide ligand and the carbene carbon [128]. As referred to before, this [2S+2SH-1C+1C0] cycloaddition reaction can be carried out with diyne derivatives, showing these reactions give better yields than the corresponding intermolecular version (Scheme 80). 

The thermal benzannulation of Group 6 carbene complexes with alkynes (the Dotz reaction) is highly developed and has been used extensively in synthesis [90,91]. It is thought to proceed through a chromium vinylketene intermediate generated by sequential insertion of the alkyne followed by carbon monoxide into the chromium-carbene-carbon double bond [92]. The realization that photodriven CO insertion into Z-dienylcarbene complexes should generate the same vinylketene intermediate led to the development of a photochemical variant of the Dotz reaction (Table 14). 

The currently known carbometallation chemistry of the group 6 metals is dominated by the reactions of metal-carbene and metal-carbyne complexes with alkenes and alkynes leading to the formation of four-membered metallacycles, shown in Scheme 1. Many different fates of such species have been reported, and the readers are referred to reviews discussing these reactions.253 An especially noteworthy reaction of this class is the Dotz reaction,254 which is stoichiometric in Cr in essentially all cases. Beyond the formation of the four-membered metallacycles via carbometallation, metathesis and other processes that may not involve carbometallation appear to dominate. It is, however, of interest to note that metallacyclobutadienes containing group 6 metals can undergo the second carbometallation with alkynes to produce metallabenzenes, as shown in Scheme 53.255 As the observed conversion of metallacyclobutadienes to metallabenzenes can also proceed via a Diels-Alder-like... 

The Dotz Reaction A Chromium Fischer Carbene-Mediated Benzannulation Reaction... 

Dotz reaction is proposed. According to our calculations the addition of the alkyne molecule to the carbene complex takes place before CO loss in the initial steps of the reaction. Further, our study shows that a novel proposal involving a chromahexatriene intermediate entails lower energy barriers and more stable intermediates than the previous reaction mechanisms postulated by Dotz and Casey. The novel findings query revision of the classically assumed paths and put forward that additional experimental and theoretical studies are necessary to definitely unravel the reaction mechanism of this intringuing reaction. 

Key words Dotz reaction, benzannulation, Fischer carbene complexes, reaction mechanism, density functional theory... 

Among the synthetically useful reactions of Fischer carbenes, the benzannulations are certainly the most prominent. In particular, the so-called Dotz reaction, first reported by Dotz in 1975 [3], is an efficient synthetic method that starting from aryl- or alkenyl-substituted alkoxycarbene complexes of chromium affords p-alkoxyphcnol derivatives by successive insertion of the alkyne and one CO ligand in an a,/Tunsaturated carbene, and subsequent electrocyclic ring closure (see Figure 1). 

Despite the undeniable synthetic value of the benzannulation reaction of aryl and alkenyl Fischer carbene complexes, the details of its mechanism at the molecular level remain to be ascertained. Indeed, although a relatively large number of theoretical studies have been directed to the study of the molecular and electronic structure of Fischer carbene complexes [22], few studies have been devoted to the analysis of the reaction mechanisms of processes involving this kind of complexes [23-30]. The aim of this work is to present a summary of our theoretical research on the reaction mechanism of the Dotz reaction between ethyne and vinyl-substituted hydroxycarbene species to yield p-hydroxyphenol. 

Before we turn to the results of our work, let us briefly summarize the relevant mechanistic information available from experimental studies and describe the mechanistic proposals presented in the literature. Figure 3 reflects the mechanistic pathways postulated for the Dotz reaction. 

The Dotz reaction mechanism has received further support from kinetic and theoretical studies. An early kinetic investigation [37] and the observation that the reaction of the metal carbene with the alkyne is supressed in the presence of external carbon monoxide [38] indicated that the rate-determining step is a reversible decarbonylation of the original carbene complex. Additional evidence for the Dotz mechanistic hyphotesis has been provided by extended Hiickel molecular orbital [23, 24] and quantum chemical calculations [25],... 

Despite these important studies, most steps of the reaction mechanism are still only postulated. Therefore, we have decided to undertake a theoretical investigation of the Dotz reaction by discussing whether the reaction proceeds via a dissociative or an associative pathway in the initial steps of the process. We have also analyzed the central part of the reaction, the key issue being whether the reaction proceeds through a vinylketene intermediate (route A) or, instead, via a metallacycloheptadienone (route B). As will be seen, we came across a novel third pathway (route C) that turns out to be the best alternative from thermodynamic and kinetic points of view... 

This section describes the main results obtained in our studies of the Dotz reaction mechanism [26-29, 39]. The section is divided as follows First, the results for the initial part of the reaction (9—>13) are presented. The central discussion will be whether the alkyne binds the carbene complex after or before CO loss. Then, the results for routes A, B and C (Figure 3) are discussed. In particular, we will examine the suitability of the novel route C involving a chromahexatriene intermediate. 

Route C in Figure 3 is a novel mechanistic proposal [28] for the central part of the Dotz reaction that invokes formation of a chromahexatriene intermediate 19 through rearrangement of the branch point species 13, followed by insertion of a CO ligand to yield 15 in the subsequent step. 

The Dotz reaction was first reported2 for an aryl carbene of the type 8, and the resulting benzannulation may be summarized conveniently as shown in Scheme 3. The major product of the reaction is usually the naphthol 9, the result of a formal [3 + 2 + 1] cycloaddition.10 In cases where CO insertion does not take place, five-membered rings (10) may also be formed. 

A particularly interesting piece of evidence concerning the nature of this sequence has been presented by Barluenga et al.21 When the vinylcarbene complex 14 was heated, decarbonylation afforded the alkene-stabilized complex 15. Upon treatment with dimethyl acetylenedicarboxylate, the alkyne-insertion product 16 was isolated. This complex proved to be unstable in solution at room temperature and decomposed readily to 17, the expected product of a Dotz reaction with an aminovinylcarbene. 

Analysis of product distributions has often been used to evince the presence of 774-vinylketenes in the Dotz reaction. Wulff has studied the reactions of a wide variety of substituted aryl chromiumcarbenes and drawn conclusions from the data that point directly toward i74-vinylketene complexes as key intermediates.13 He has also isolated40 bicyclic lactone products (e.g., 23) characteristic of a van Halban-White cyclization41-44 from the reaction of vinylcarbenes and ketoalkynes. These bicyclic lactones are not generally... 

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