Alkynes enyne constructs

In analogy with the strategy of carbocyclic construction, 1,6-enynes containing an oxygen heteroatom in the carbon atom sequence have been used for 3,4-disubstituted tetrahydrofuran synthesis. The simplest example is given by the hydrosilylation of enyne at room temperature (Reaction 7.38) [49]. Tetrahydrofurans with an exocyclic methylene functionality can also be prepared from the appropriate alkynes, such as 32, with (TMS)3SiH in refluxing benzene which afforded exclusive formation of the exomethylene in the Z conformation (Reaction 7.39) [50]. 

Metathesis reactions are now widely used in natural product synthesis. Novel retrosynthetic analyses were developed because a carbon-carbon single bond can be formed after hydrogenation of a double bond constructed by metathesis. Although many types of metathesis are now known, the reaction is classified by olefin, enyne, and alkyne metatheses in this chapter. 

Due to the copious amount of recent literature pertaining to olefin CM, a comprehensive review would prove repetitive, as this reaction is now a widespread synthetic tool. Fortunately, numerous reviews are now readily available on this subject. This chapter therefore focuses on reports pertaining to important aspects in either the concept or the application of alkene CM. Allene, alkyne, and enyne CM reactions are not included within the scope of this review. Drawing from the examples discussed, a series of general guidelines toward constructing a desired olefin CM transformation will be presented. 

The intramolecular Alder-ene reaction (enyne cydoisomerization reaction) with alkynes as the enophiles has found wide application compared with diene systems. The reason may be the ready chemo-differentiation between alkene and alkyne functionality and the more reactive alkyne moiety. Furthermore, the diene nature of the products will promote further applications such as Diels-Alder reactions in organic synthesis. Over the past two decades the transition metal-catalyzed Alder-ene cycloisomerization of l,n-enynes (typically n= 6, 7) has emerged as a very powerful method for constructing complicated carbo- or heterocydic frameworks. The transition metals for this transformation indude Pd, Pt, Co, Ru, Ni-Cr, and Rh. Lewis acid-promoted cydoisomerization of activated enynes has also been reported [11],... 

Enyne systems are also capable of impressive multiple RRM transformations. For the first such example see Ref. [119]. The reaction of a ruthenium alkyli-dene with an alkyne produces a new vinyl alkylidene, which can participate in further intramolecular or intermolecular metathesis reactions to form fused ring systems. This has led Grubbs to designate alkynes in such systems as relays . In a noteworthy example, Zuercher et al. [ 120] constructed the four fused rings of the steroid backbone 68 in one efficient step using tandem enyne re-... 

The most recent contribution in this area is by Shea who prepared tricyclic oxygen containing heterocycles from acyclic enynes 82 using a combination of intramolecular Nicholas and PKRs. They constructed [5.7.5] and [5.8.5] (83-84) systems involving the formation of a complexed cyclic alkyne. They used several PKR conditions that give different yields and diastereo-selectivities. Due to the strain of the intermediate, [5.6.5] systems (85) were obtained in poor yields (Scheme 24) [121]. 

A number of cycloisomerization reactions of enynes to construct five-membered car-bocycles with a variety of transition metal catalysts have been reported thus far [24]. The mechanisms that have been proposed for the cycloisomerization of enynes include 1) hydrometallation of alkyne followed by carbometallation of the olefin ... 

Transition metal catalyzed intermolecular carbocyclization has been used in the construction of six-membered ring systems (10, 352) and provides a powerful approach to the construction of complex polycyclic systems. The rhodium-catalyzed intermolecular [2 - - 2 - - 2] carbocychzation of heteroatom-tethered 1,6-enynes with symmetrical and unsymmetrical alkynes affords the corresponding bicyclohexadienes in a highly efficient and regioselective... 

As described above (Section 5.2), the Stephens-Castro reaction of alkynylcopper with aryl and vinyl halides in boiling pyridine is a useful route to aryl and vinyl acetylenes. Direct cross-coupling of organic halides, such as sp2 halides, with terminal alkynes is a more convenient procedure. Such a reaction is not so easy, but it can be done using a Pd-complex catalyst [41]. Especially facile Pd-catalyzed cross-coupling of aryl and alkenyl halides with terminal alkynes proceeds smoothly under mild conditions in the presence of a cocatalyst of cuprous iodide in amine solvents [Eq. (28)] [42], This methodology is now used widely for the construction of conjugated arylalkyne or enyne systems [43], as described below. It is attractive from a synthetic point of view because mild reaction conditions and simplicity of the procedure are associated with recent developments in modern acetylene chemistry [44],... 

Shibata and co-workers independently developed similar [2-I-2-I-2] cycloaddition of enynes 13 (Scheme 6) and alkynes 14, affording cyclohexadienes 15 (15). The significance of this work is the construction of quaternary carbon stereocenters, which remain a very challenging task in organic synthesis (16). The authors... 

Yoshida and Imamoto have also described a variation of the previous strategy, where the aUcene and alkyne undergoing the enyne metathesis reaction are intramolecular variants [37]. In this work, a range of styrene-containing compounds was synthesized, and two specific examples are shown in Scheme 17.18. In the first example (91 92), the triene intermediate 93 was constructed from the enyne substrate 91 using 2-Ru as a catalyst. This compound underwent aromatization to yield the desired styrene 92. In this example, the reaction was only successful when the hydroxyl group of 91 was protected as the 0-acetate. For the second reaction (94->-95) shown in Scheme 17.18, it is interesting to note that the enyne metathesis reaction of 94 resulted in the substituted (1-phenylvinyl)benzene 95. 

In this subchapter, I summarized the intermolecular two-component cycloaddition reactions, which are able to construct benzenoid aromatic rings. Four types of transition metal-catalyzed [4-r2] cycloaddition reactions (Diels-Alder reactions, reactions of enynes with alkynes, reactions via pyrylium intermediates, and reactions via acylmetallacycles) are described. 

Various cyclohexadienes can be obtained through the rhodium-catalyzed cyclotrimerization of 1,6-diynes with alkenes [12] or 1,6-enynes with alkynes [13], Valorization of these cyclohexadienes was reported with the development of original tandem [2-I-2-I-2] cycloaddition/[4-l-2] Diels-Alder cascades. For example, Tanaka and coworkers recently achieved the construction of bridged polycyclic lactam products, by performing a [2-1-2-1-2] cycloaddition/[4-l-2] Diels-Alder cascade between... 

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