Enynes special

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 allylic 2-alkynoates 77 are a group of special enynes with an ester linkage between their double bond and triple bond. When halopalladation of the triple bond is followed by C-C double bond insertion and the cleavage of the carbon-palladium bond, a series of y-lactones (78-81) can be obtained. 

The presence of a methyl substituent at the acetylenic terminus of the enyne-allenes 28e-n appears to reduce the rate of cydization, presumably for steric reasons. The higher thermal stability allows their isolation and purification at ambient temperature without special precautions. 

Allenic amino acid derivatives 50, which are of special interest as selective vitamin Bg decarboxylase inhibitors [35], are accessible through 1,6-cuprate addition to 2-amino-substituted enynes 49 (Eq. 4.22) [36]. Because of the low reactivity of these Michael acceptors, however, the reaction succeeds only with the most reactive cuprate the t-butyl cyano-Gilman reagent tBu2CuLi-LiCN. Nevertheless, the addition products are obtained with good chemical yields, and selective deprotection of either the ester or the amino functionality under acidic conditions provides the desired target molecules. 

In general, this synthesis of enynes has no special advantages over the alternative method which starts with allenylmagnesium bromide [144] ... 

Z)-vinylic tellurides are the source of enynes 212 and enediynes 213 by transformation into vinylcopper species (Section 9.13.8.2.4), followed by reaction with haloalkynes (Scheme 113).278,279 The transformation occurs with retention of the double-bond stereochemistry. This is an efficient and straightforward route to important unsaturated units present in natural products, specially in enediyne antibiotics.280... 

Such cumulenic derivatives cannot be obtained by isomerization of acetylenic precursors under catalytic conditions, since they are thermodynamically less stable than the acetylenes. Special conditions for the protonation of metallated acetylenic sulfides and metallated enyne amines are described in Refs. [7] and [106] and in Chap. IV, Exp. 19. 

Allylic alkynoates are a group of special enynes with an electron-deficient triple bond and an ester linkage between the double bond and triple bond. Based on the reaction described in Sect. B.iv.a, an intramolecular version could be developed, for example, au a-alkylidene-y-butyrolactone structure could easily be assembled through halopallada-tion, carbon-carbon double bond insertion, and dehalopalladation " (Scheme 13). The mechanism may be sununatized as shown in Scheme... 

As simple allenic ethers (R = H) and 1,2,3-trienyl ethers (R = R = H or alkyl) are readily accessible, the 1,3-substitution method constitutes a good method for the synthesis of some special acetylenes and enynes, e.g. HCsCCHaPh and C2H50-CH=C(CH3)-CeCH. 

In the special case of 1,7- and 1,8-enynes seven-membered rings are obtained by a 1-exo-dig cyclization when the alkene moiety is a silylenolether [196]. 

The close relationship of cyclization modes existed in sesquiterpene biosynthetic machinery, with those presented by the metal-catalyzed cycloisomerizations, justify the vast amount of reports on total synthesis of sesquiterpenes, in which the utilization of enyne or diene cycloisomerizations are the key components of their synthetic strategy. This chapter is intended to cover only selected examples on the topic. Special concern is given on covering catalyzed reactions, which are triggering different cyclization modes, only for the construction of sesqniterpene core strnctnres. Assuredly, cycloisomerization reactions are powerfnl tools in providing also other classes of secondary metabolites, as complex terpenoids and alkaloids, in which the readers are referred to more general reviews on the topic [26,30]. 

The thermal reaction of benzannelation of enediynes, the Bergman cycloaromatization, that occupies a special place, has been intensively studied [16]. These methods include also the less studied Myers-Saito [17] and Schmittel [18] cycloaromatization. Cycloaromatization of enediyne and enyne-allene blocks is described in books [19-23] and revietvs (Scheme 1.2) [24-30]. 

There is only one example in the literature where an enyne RCM coupled to an intermolecular CM in a sequence process has been applied in the synthesis of a natural product. The synthesis of (-i-)-8-epi-xanthatin, isolated from the leaves extracts from Xanthium canadense, was proposed by Martin et al. through an enyne RCM-CM cascade combining ring closing of 8 with a CM with 9 [13]. The special challenge for this transformation consists in the use of an electron-poor olefin for the final metathesis reaction. The use of [Ruj-III (20mol%), the catalyst of choice for this type of transformations [14], and an excess (10 equiv.) of the methyl vinyl ketone 9 resulted in the formation of the desired product in 83% yield (Scheme 11.3). 

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