Enynes, metathesis chemistry

Intermolecular-enyne metathesis, if it is possible, is very unique because the double bond of the alkene is cleaved and each alkylidene part is then introduced onto each alkyne carbon, respectively, as shown in Scheme 9. If metathesis is carried out between alkene and alkyne, many olefins, dienes and polymers would be produced, because intermolecular enyne metathesis includes alkene metathesis, alkyne metathesis and enyne metathesis. The reaction course for intermolecular enyne metathesis between a symmetrical alkyne and an unsym-metrical alkene is shown in Scheme 9. The reaction course is very complicated, and it seems impossible to develop this reaction in synthetic organic chemistry. 

We will focus on the development of ruthenium-based metathesis precatalysts with enhanced activity and applications to the metathesis of alkenes with nonstandard electronic properties. In the class of molybdenum complexes [7a,g,h] recent research was mainly directed to the development of homochi-ral precatalysts for enantioselective olefin metathesis. This aspect has recently been covered by Schrock and Hoveyda in a short review and will not be discussed here [8h]. In addition, several important special topics have recently been addressed by excellent reviews, e.g., the synthesis of medium-sized rings by RCM [8a], applications of olefin metathesis to carbohydrate chemistry [8b], cross metathesis [8c,d],enyne metathesis [8e,f], ring-rearrangement metathesis [8g], enantioselective metathesis [8h], and applications of metathesis in polymer chemistry (ADMET,ROMP) [8i,j]. Application of olefin metathesis to the total synthesis of complex natural products is covered in the contribution by Mulzer et al. in this volume. 

The skeletal rearrangements are cycloisomerization processes which involve carbon-carbon bond cleavage. These reactions have witnessed a tremendous development in the last decade, and this chemistry has been recently reviewed.283 This section will be devoted to 7T-Lewis acid-catalyzed processes and will not deal, for instance, with genuine enyne metathesis processes involving carbene complex-catalyzed processes pioneered by Katz284 and intensely used nowadays with Ru-based catalysts.285 By the catalysis of 7r-Lewis acids, all these reactions generally start with a metal-promoted electrophilic activation of the alkyne moiety, a process well known for organoplatinum... 

Enyne metathesis is unique and interesting in synthetic organic chemistry. Since it is difficult to control intermolecular enyne metathesis, this reaction is used as intramolecular enyne metathesis. There are two types of enyne metathesis one is caused by [2+2] cycloaddition of a multiple bond and transition metal carbene complex, and the other is an oxidative cyclization reaction caused by low-valent transition metals. In these cases, the alkyli-dene part migrates from alkene to alkyne carbon. Thus, this reaction is called an alkylidene migration reaction or a skeletal reorganization reaction. Many cyclized products having a diene moiety were obtained using intramolecular enyne metathesis. Very recently, intermolecular enyne metathesis has been developed between alkyne and ethylene as novel diene synthesis. 

Despite its difficulty, intermolecular enyne metathesis has been developed and will be a very important reaction in synthetic organic chemistry. It is expected that many interesting and useful applications will be developed in the future. 

Ring-closing metathesis of an enyne, which has double and triple bonds in the molecule, is a remarkable reaction which is useful in synthetic organic chemistry. In enyne metathesis, the double bond is cleaved and carbon-carbon bond formation occurs between the double and triple bonds. The cleaved alkylidene part is moved to the alkyne carbon. Thus, the cyclized compound formed in this reaction has a diene moiety [Eq. (6.77)]. The reaction is also called skeletal rearrangement and is induced by Pt, Pd, Ga, and Ru catalysts ... 

Species (A) and (B) constitute the main class of unsaturated carbenes and play important roles as reactive intermediates due to the very electron-deficient carbon Cl [1]. Once they are coordinated with an electron-rich transition metal, metal vinylidene (C) and allenylidene (D) complexes are formed (Scheme 4.1). Since the first example of mononuclear vinylidene complexes was reported by King and Saran in 1972 [2] and isolated and structurally characterized by Ibers and Kirchner in 1974 [3], transition metal vinylidene and allenylidene complexes have attracted considerable interest because of their role in carbon-heteroatom and carbon-carbon bond-forming reactions as well as alkene and enyne metathesis [4]. Over the last three decades, many reviews [4—18] have been contributed on various aspects of the chemistry of metal vinylidene and allenylidene complexes. A number of theoretical studies have also been carried out [19-43]. However, a review of the theoretical aspects of the metal vinylidene and allenylidene complexes is very limited [44]. This chapter will cover theoretical aspects of metal vinylidene and allenylidene complexes. The following aspects vdll be reviewed ... 

Important progress has been made in the study of the process since the discovery and development of well-defined ruthenium carbene complexes. The interest in the reaction as a synthetic tool for organic synthesis has been growing, among others, because of its atom economy. For recent reviews on enyne metathesis see Refs. [91-93]. For a review on the application of enyne metathesis in organosilicon chemistry see Ref. [6]. 

A branching pathway based on the chemistry of Michael adducts (7) was developed by Porco (Scheme 27.2) [47]. Reduction of the nitro group triggered lactamization to yield y-lactams such as 8. In contrast, with appropriately positioned alkenyl and alkynyl substituents, cyclization via ring-closing metathesis or Pauson-Khand reaction was possible. With =allyl and R =C=CCH20Me, enyne metathesis yielded the cyclic diene 9. In contrast, with R =C=CH and R = allyl, a Pauson-Khand reaction allowed the remarkable bridged cyclopentenone 10 to be obtained. 

Although intermolecular enyne metathesis is the simplest to envision, intramolecular enyne metathesis was the major focus of the initial work. Two representative intramolecular enyne meta theses are shown in Equations 21.44 and 21.45. The reaction in Equation 21.44 shows the value of this chemistry to form heterocycles. The reaction in Equation 21.45 shows how enyne metathesis can be used in combination with olefin metathesis to form bicyclic products. The initial enyne metathesis process in Equation 21.45 terminates in a ruthenium carbene complex. The carbene complex is then trapped by the remaining olefin in a [2+2] and retro-[2+2] cycloaddition sequence to generate the bicyclic organic product and a ruthenium carbene complex that re-enters the catalytic cycle by reaction witii the yne diene. 

Since the 1990s, the olefin metathesis reaction has become a major synthetic tool in organic chemistry. Organoboranes were first employed in the construction of carbo-cyclic and heterocyclic alkenylboronates by ring closure of the corresponding acyclic precursors [104], Ruthenium-catalyzed enyne metathesis of acetylenic boronates was later demonstrated as a concise route for the construction of cyclic 1,3-dienylboronic esters, which can be further engaged in [4-i-2] cycloadditions (Scheme 9.51) [86]. 

Metathesis reactions are very powerful tools to create C—C bonds and provide synthetic chemists with synthetic design based on an unprecedented retrosynthetic analysis of complex compounds in very elegant and efficient ways. As the impact of metathesis in modern synthetic chemistry of drug and natural product is evidenced by a number of publications and reviews, in this chapter, we describe the most illustrative strategies of metathesis and their applications to drug and natural product syntheses in line with types of olefin, enyne, and alkyne metathesis reactions. 

Phosphorus is a key element in catalysis, and the last two Nobel prizes in molecular chemistry were awarded to Noyori, Sharpless and Knowles (2001) for their work on enantioselective catalysis and to Grubbs, Schrock and Chauvin (2005) for their work on the chemistry of transition metal carbene complexes and their applications in metathesis. In both cases the development of highly efficient, specifically tailored phosphorus based ligands are of paramount importance The book opens with an account of the recent studies on a new family of air-stable chiral primary phosphines based on the binaphthyl backbone and their applications in asymmetric hydrosilylations (Chap. 1). The concept of applying phosphorus ligands to enantioselective catalysis is also the main subject of Chaps. 5 and 10, dealing with P-based planar chiral ferrocenes and chiral phosphorus ligands for enantioselective enyne cycloisomerizations, respectively. 

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