Metathesis cross-enyne

Enyne Cross Metathesis and Ring-Closing Enyne Metathesis.348... 

Fig. 2a-c Typical enyne metathesis reactions ring-closing enyne metathesis (a) enyne cross metathesis (b and c)... 

The olefin cross metathesis (CM) can be described as the intermolecular metathesis of alkylidene fragments between two different olefins [133]. It can be farther divided into three main subtypes cross metathesis, ring opening cross metathesis (ROCM) and enyne cross metathesis (ECM) (Scheme 3.9). 

The enyne cross metathesis was first developed in 1997 [170,171]. Compared to CM it benefits from its inherent cross-selectivity and in theory it is atom economical, though in reality the aUcene cross-partner is usually added in excess. The inabihty to control product stereochemistry of ECM reactions is the main weakness of the method. ECM reactions are often directly combined with other transformations like cyclopropanation [172], Diels-Alder reactions [173], cychsations [174] or ring closing metathesis [175]. 

The intermolecular enyne cross metathesis, and consecutive RCM, between a terminal alkyne and 1,5-hexadiene produces cyclohexadienes, by cascade CM-RCM reaction, and trienes, formed during the sole CM step. Studies of various parameters of the reaction conditions did not show any improvement of the ratio of desired cyclohexadiene product [25] (Scheme 12). The reaction with cyclopentene instead of hexadiene as the alkene leads to 2-substituted-l,3-cycloheptadienes [26]. After the first cyclopentene ROM, the enyne metathesis is favored rather than ROMP by an appropriate balance between cycloalkene ring strain and reactivity of the alkyne. 

In contrast to the reliable, high-yielding, and selective intramolecular, n-enyne metathesis reaction, intermolecular enyne metathesis (enyne cross-metathesis) has seen less use in the synthesis of complex molecules due to limited selectivity, despite its potential in fragment-coupling processes (404). The most common use of intermolecular enyne metathesis employs ethylene as the alkene component, providing a particularly convenient method for the production of... 

Scheme 68. Use of Ru-carbene catalyst for enyne cross-metathesis to generate 2,3-butadienes.

Scheme 69. Second-generation Grubbs catalyst applied to intermolecular enyne cross-metathesis for the preparation of anoUgnan. (Mes = Mesityl Cy = cyclohexyl Ms = mesylate.)...

Scheme 73. Formation of disubstituted benzenes by [4 + 2] enyne cross-metathesis at Pd(0).

Treatment of an alkyne/alkene mixture with ruthenium carbene complexes results in the formation of diene derivatives without the evolution of byproducts this process is known as enyne cross-metathesis (Scheme 22). An intramolecular version of this reaction has also been demonstrated, sometimes referred to as enyne RCM. The yield of this reaction is frequently higher when ethylene is added to the reaction mixture. The preferred regiochemistry is opposite for enyne cross-metathesis and enyne RCM. The complex mechanistic pathways of Scheme 22 have been employed to account for the observed products of the enyne RCM reaction. Several experiments have shown that initial reaction is at the alkene and not the alkyne. The regiochemistry of enyne RCM can be attributed to the inability to form highly strained intermediate B from intermediate carbene complex A in the alkene-first mechanism. Enyne metathesis is a thermodynamically favorable process, and thus is not a subject to the equilibrium constraints facing alkene cross-metathesis and RCM. In a simple bond energy analysis, the 7r-bond of an alkyne is... 

Scheme 23 Representative examples of enyne cross-metathesis.

Scheme 24 Cycloaddition through tandem enyne cross-metathesis-RCM.

Under enyne cross-metathesis conditions, the intermolecular reaction of the a,(D-dienes 153, derived from the MBH reaction, with different terminal alkynes 154 afforded triene intermediates that cyclized spontaneously under the reaction conditions to give substituted cis-hexahydro-l/f-indenes 155 (Scheme 4.45), which can be further transformed into steroid analogues via TBS deprotection and oxidation. However, metathesis reactions starting with 156 only furnished trienes 157 [as EfZ) mixtures] and no spontaneous intramolecular cycloaddition occurred. Even at elevated reaction temperatures, trienes 157 cyclized only slowly to give octahydronaphthalene diastereomers. With deprotection of the TBS and subsequent Dess-Martin oxidation, trienes 157 could be converted exclusively into cw-fused 7-substituted 6,7-dehy-drodealone-l-one-lO-carboxylic esters 158 in 50-60% yields. Moreover, c ross-metathesis of TBS-unprotected MBH adduct 159 with alkynes 154 along with treatment with Dess-Martin periodinane (DMP) in one pot could conveniently produce the corresponding bicyclic ketones 160 in moderate yields. ... 

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