Diene bicyclic, metathesis

Olefin metathesis of a conjugated diene has recently been exploited by Hiemstra et al. for the synthesis of bicyclic analogs of 116. Second-generation... 

The symmetrical dienyne 58a was converted to a fused bicyclo [4.3.0] ring in 95% yield [17] (Eq. 27). With substrate 58c containing an unsymmetrical diene tether, two different products, 59c and 59c, were obtained in a ratio of 1 to 1 (Eq. 28). The reaction course in the formation of the different bicyclic rings is shown in Scheme 8. This dienyne metathesis is also catalyzed by tungsten or molybdenum complex 62 or 63 (Fig. 1), and a dienyne bearing terminal alkyne 58b could be cyclized to give 59b in 97% yield. 

The synthesis of bicyclic 2-azetidinones 154 has been accomplished by ringclosing metathesis reaction of monocyclic diene- and enyne-(3-lactams. The enyne metathesis of compounds 153 afforded bicycles 154 in good yields (Scheme 52) [92]. 

As part of a program exploring functionalized bicyclic /3-lactams, the ring-closing metathesis of the /3-lactam diene 46 in the presence of a molybdenum-based catalyst (5 mol%) was shown to afford access to the fused 1,3-thiazepine 47 in 78% yield (Equation 7) <1997CC155>. 

Murai et al. showed that the cycloisomerization of enynes catalyzed by PtCl2 has several feasible pathways (1) to 1,3-dienes via a formal metathesis, (2) to a 1,4-diene if the enyne substrates contains an allylsilane or stannane, (3) to a homo-allylic ether if it the reaction is performed in an alcoholic medium, or (4) to bicycle[4.1.0]heptene derivatives (Scheme 4) [26]. Further studies conducted by other groups have indicated the cyclization might proceed via a cationic mechanism triggered by coordination of Pt(II) with the alkyne moiety [27, 28]. Very recently, Oi and coworkers also observed a formal metathesis reaction mediated by a cationic Pt complex [29]. 

Vinyl carbene intermediates can also be generated from the intermolecular addition of TMS diazomethane onto an alkyne component in the presence of Ni(cod)2 as a catalyst. If a diene moiety is also present, as in 1,6-enyne system 78, reaction of the intermediate nickel carbenoid with this partner gives birth to the fused 5,7-bicyclic system 79 in fair yields (Scheme 34). Several mechanistic scenarios are possible from generic precursor 78, including a metathesis-type sequence to generate a nickelacyclobutane 80, followed by... 

Recently, a catalytic system consisting of a second generation Grubbs catalyst or an in situ non-carbenic ruthenium complex have allowed a cascade catalytic reaction of cyclopropanation/ring closing metathesis of dienynes containing a malonate or bissulfone moiety. In this reaction, the interaction between the triple bond and one double bond gives a bicyclic product via cyclopropanation, and then the subsequent diene RCM produces the last cyclization step [16] (Scheme 6). 

Interesting compounds that have been acquired from the metathesis process include bicyclic P-lactams (also those comprising a diene unit by the enyne metathesis ), a-stannyl cyclic ethers, cyclic siloxanes which can be opened to afford (Z)-alkenediols, spiroannulated dihydrofurans and dihydropyrans, and [2]catenanes from precursors organized by Cu(I). ... 

Scheme 71. The Rh-catalyzed cross-enyne metathesis for the preparation of bicyclic 1,3-dienes.

In the two separate, initial reports on the reactivity of Fischer carbenes with enynes, one study found cyclobutanone and furan products [59], while the other found products due to olefin metathesis [60]. These products have turned out to be the exceptions rather than the rule, as enynes have since been found to react with Fischer carbenes to produce bicyclic cyclopropanes quite generally. The proposed mechanistic pathway is included as part of Bq. (28), in which vinylcarbene 10, produced by insertion of the alkyne into the metal carbene, may then cyclize with the pendant olefin to metallacyclobutane 11, leading to product. The first reported version of this reaction suffered from extreme sensitivity to olefin substitution [Eq. (28) compare R=H, Me] often producing side-products due to metathesis (through 11 to yield dienes) and CO insertion (into 10 to yield cyclobutanones and furans) [61]. Since then, several important modifications have been developed which improve yield, provide greater tolerance for alkene substitution, and increase chemoselectivity for the bicyclic cyclopropane... 

Enyne metathesis RCM can be performed in tandem with RCM using appropriately spaced diene-yne substrates. Many examples of this reaction featuring various degrees of complexity have been reported. Representative examples of tandem enyne metathesis-RCM are depicted in Scheme 30 and include (i) formation of the fused bicyclic compound 257 from dienyne 255 for securinine total synthesis/ (ii) synthesis of cyclic ethers (e.g., 261 and 262) from diene-alkynes (e.g, 258) and control of the product distribution through alkene substitution pattern,and (iii) double tandem RCM-enyne metatheses (conversion of 263 into 266) of appropriate polyene-polyyne systems. 

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. ... 

Next to fused bicyclic systems, the domino dienyne metathesis process can also be applied to the construction of bridged bicyclic dienes. Thus, dienyne 110 bearing differently substituted alkene units to ensure a regiocontrolled cyclization readily afforded the taxosteroid hybrid compound 111 without competing cyclopentene formation in the presence of the Grubbs second-generation catalyst 2 (Scheme 2.40) [19]. 

Using a disubstituted aUcyne with appropriately placed alkenes at either side, the domino dienyne metathesis also enables the formation of bicyclic 1,3-dienes where two cyclic olefins are connected by a C-C single bond [20]. Scheme 2.41 depicts such a scenario for the double cyclization of diether 112 to give a virtually quantitative yield of the bisdihydrofuran 113 with Grabbs catalyst 1 [20a,cj. 

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. 

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