Cis-enyne

Conjugated diynes can be reduced to cis enynes by the well-known hydroboration-protonolysis sequence . cw-5-Dodecen-7-yne (215) is obtained from the diyne 213 in 76% yield as shown in equation (23). The orientation of addition of the disiamyl-borane was established by using CH3CO2D in the second step. Addition of a second mole of disiamylborane to 214 is very slow, but reduction to the cis,cis diene can be accomplished by using dicyclohexylborane instead . 

The method was used for attachment of the cis enyne side chain in a synthesis of gephyrotoxin, and for the preparation of (Z)-non-3-en- 1-yne, a building block in the synthesis of prostaglandins and of 11-HETE methyl ester. ... 

The development of the oxazolidinone catalyst has allowed Shi to further increase the scope of the epoxidation to a range of new substrates. Using ketone catalyst 5 styrene is epoxidized with 24% ee, while the use of oxazolidinone 13a for the same transformation gave 86% ee, with further improvement in enantioselectivity seen with the inclusion of electron-donating substituents on the aromatic ring of the styrene substrates [43]. ds/trans-Dienes and trienes were epoxidized regioselectivity at the ds-alkene and no isomerization or further epoxidation of the products were observed [44], while epoxidation of conjugated cis-enynes resulted in chemoselective epoxidation of the alkene [45]. 

Holmes, A. B., R. A. Raphael, and N. K. Wellard Model studies in the histrionicotoxin series A highly stereoselective synthesis of terminal cis enyne units. Tetrahedron Letters 1976, 1539—1542. 

In general, hydroboration—protonolysis is a stereoselective noncatalytic method of cis-hydrogenation providing access to alkanes, alkenes, dienes, and enynes from olefinic and acetylenic precursors (108,212). Procedures for the protonolysis of alkenylboranes containing acid-sensitive functional groups under neutral or basic conditions have been developed (213,214). 

The standard Sonogashira reaction conditions were not successful for the coupling reaction of 3-chloropyrazine 1-oxide (40) and 1-hexyne. In contrast, treatment of 40 and 1-hexyne with Pd(Ph3P)4 and KOAc produced 3-(l-hexynyl)pyrazine 1-oxide (41), together with the co-dimeric product, (E)-enyne 42 [34]. Presumably, the co-dimerization product 42 resulted from the cis addition of 1-hexyne to adduct 41. 

In this approach, the cis-disubstituted tetrahydrofuranone 75 [accessible with high diastereoselectivity via radical cyclization of the acylselenide 74 with tris(tri-methylsilyl) silane and triethylborane] was transformed into the corresponding enyne 76 by reduction and Wittig olefination. The subsequent electrophilic cyclization was carried out in analogy with the biomimetic synthesis of panacene (Scheme... 

Styrenes [103], conjugated aT-dienes [107], and aT-enynes [108] are also epoxidized with ketones 57 in high ees (Table 5, entries 9-14). No isomerization of the epoxides was observed therefore only c/x-epoxides were obtained from cis-olefins. Alkenes and alkynes appear to be effective directing groups to favor the desired transition states T and V (Fig. 19). 

Molander has developed effective protocols for the cyclization/hydrosilylation of 1,6-enynes catalyzed by lanthanide metallocene complexes/ For example, reaction of cyclohexyl-substituted 1,6-enyne 15a with phenylsilane catalyzed by Cp 2YMe(THF) in cyclohexane at room temperature for 2h gave silylated alkylidene cyclopentane 16a as a 6.5 1 mixture of trans. cis isomers (Table 5, entry 1). The diastereoselectivity of the reaction depended strongly on the nature of the allylic substituent. For example, yttrium-catalyzed cyclization/ hydrosilylation of the ethyl-substituted enyne 15b gave silylated cyclopentane 16b in 88% yield as a single diastereomer (Table 5, entry 2). 

Lanthanide-catalyzed enyne cyclization/hydrosilylation was also applied to the synthesis of silylated alkylidene cyclohexane derivatives. For example, reaction of the 3-silyloxy-l,7-enyne 17 with methylphenylsilane catalyzed by Gp 2YMe(THF) at 50°G for 8h gave 18 in quantitative yield as a 4 1 mixture of trans cis isomers (Equation (11)). Employment of methylphenylsilane in place of phenylsilane was required to inhibit silylation of the initially formed yttrium alkenyl complex, prior to intramolecular carbometallation (see Scheme 8). 

Dienes are less reactive toward transition metals than enynes and diynes, and perhaps for this reason, the development of effective catalyst systems for the cyclization/hydrosilylation of dienes lagged behind development of the corresponding procedures for enynes and diynes. The transition metal-catalyzed cyclization/hydrosilylation of dienes was first demonstrated by Tanaka and co-workers in 1994. Reaction of 1,5-hexadiene with phenyl-silane catalyzed by the highly electrophilic neodymium metallocene complex Cp 2NdCH(SiMe2)3 (1 mol%) in benzene at room temperature for 3 h led to 5- ///76 -cyclization and isolation of (cyclopentylmethyl)phenylsilane in 84% yield (Equation (15)). In comparison, neodymium-catalyzed reaction of 1,6-heptadiene with phenylsilane led to 5- X(9-cyclization to form (2-methylcyclopentylmethyl)phenylsilane in 54% yield as an 85 15 mixture of trans. cis isomers (Equation (16)). 

Highly stereoselective cis additions of organocuprates to alkynic esters have also been reported with alkylcopper-Lewis acid complexes.3 The choice of the proper Lewis acid was found to be important in determining the stereoselection as was demonstrated with enyne (32 Table 2).5- 8 While both the diorga-nocuprate and the alkylcopper-BF3 complex gave mixtures of stereoisomers, the Bu u-BEts provided... 

A palladium-cataly/ed 1,6-enyne cycli/ation of the Tmst20 type provides the desired bicyelic system as a mixture of hexahydro-5//-1-pyrindine 14-Z and its double-bond isomer 15-Z in a ratio of 97 3. The two can be separated by column chromatography In the process, the exocyclic alkylidene sidechain is created with Z selectivity, and the rings are stereo specifically joined cis. It should be noted that only with the use of BBEDA [A V -bis(benzylidene)ethylene diamine] as a powerful a-donor ligand is high Z selectivity achieved Other catalytic systems, such as Pd(OAc) or Pd(OAc) ifPPhOVHOAc produce EfZ mixtures of 14 and 15 in ratios of 45 25 27 3 or 9 69 6 16 (14-Z 15-Z 14-E 15-E). 

Mononuclear ruthenium complexes have become useful catalysts, not only because they can have high regio- and stereoselectivity but also because their catalyzed reactions rely on an elucidated mechanism. This true for the cis-dihydride (PP3)RuH2 complex, a catalyst precursor for the selective head-to-head dimerization of phenylacetylene to the corresponding (Z)-enyne, via bis(alkynyl) active spe-... 

C-H activation pathway cannot be ruled out for this transformation, however. They subsequently observed C-H insertion of a cis substituent by means of isotope studies [32], The cycloheptene product was observed as the major product when cis- or tri-substituted enyne and acetylenic ester termini were present. Ruthenium hydride catalysts reported by Mori and Dixneuf can also initiate the cycloisomerization of 1,5- and 1,6-enynes and dienes [33, 34], The vinylruthenium hydride can be obtained from RuClH(CO)(PPh3)3 or in the presence of acetic acid or ethanol. 

Figure 16.32 represents the alkenylation of an acetylene according to the procedure developed by Cacchi. The coupling partners are an alkenyl triflate (prepared in analogy to Figure 13.23) and an alkyne. The coupling product of these compounds is a 1,3-enyne—in this case conjugated with a cyclohexenone. The C=C triple bond of such an enyne can be hydrogenated in a cis-selective fashion by using Lindlar s Pd catalyst (cf. Figure 17.81). In this way 1,3-dienes are formed that contain at least one cij-configured C=C double bond.

Dienylsilanes 3 and 6 are the cis and trans addition products of hydrosilanes across the triple bond of 1, respectively. Allylsilane is the product formed by hydrogenation followed by hydrosilylation of 1. Alkenylsilane 5 is the 1,4-adduct of hydrosilane across the enyne skeleton of 1, andbis(silyl)butenyne 7 is the de-hydrogenative silylation product of 1 [32]. 

It is often more convenient, as in the Heck reaction, to use a stable and soluble Pd(II) derivative such as bis(triphenylphosphine)palladium(II) chloride instead of Pd(0). This is rapidly reduced in situ to give a coordinatively unsaturated, catalytically active, palladium(O) species. The geometry of the alkene is generally preserved so that cis (Z) and trans (E) dichloroethylene give the two different geometrical isomers of the enyne below in >99% stereochemical purity as well as excellent yield. 

Equally, a 1.5 1 mixture of cis- and frans- 1,3-dibromo propene reacts with sodium dimethyl methylmalonate to furnish the vinyl bromo derivative 79 in excellent yield, which in turn is transformed in a one-pot fashion to a 1.5 1 mixture of enyne 80 or the corresponding Suzuki products 81 and 82 (Scheme 24). Interestingly, (( )-3-bromo-propenyl)-tributylstannane furnishes the vinyl stannane 83 upon allylic substitution that instantaneously is subjected to the conditions of a Stille coupling with iodo benzene to give the sequence s product 84 in 68% yield (Scheme 25). 

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