Grubbs-I catalyst

Although the metathesis of ene-ynes is a valuable method for the preparation of 1,3-butadienes, and may be used for Diels-Alder reactions, a problem arises from the need to employ either a high temperature or a Lewis add to accelerate the cycloaddition, which is usually not feasible with the Grubbs catalyst Therefore, the combination of metathesis and cycloaddition is usually performed in sequential fashion (as just shown, and highlighted earlier) [264]. However, Laschat and coworkers [265] have shown the Lewis acid BC13 to be compatible with the Grubbs I catalyst (6/3-13). Reaction of 6/3-92 and ethyl acrylate using a mixture of 2.5 equiv. of the Lewis acid and 10 mol% of 6/3-13 led to 6/3-93 in 60% yield (Scheme 6/3.27). 

As shown in the two examples described here, formation of the benzene nucleus by trimerization of alkynes is usually catalyzed by a Co-complex. However, Und-heim and coworkers [276] have recently shown that a Ru "-complex can also be used. Reaction of the triyne 6/4-9, which was prepared from SchollkopPs bislactim ether 6/4-8 [277] with Grubbs I catalyst 6/3-13, led to 6/4-10 in an excellent yield of 90%. Hydrolysis of 6/4-10 gave the desired as-indacene-bridged bis(a-amino acid) derivative 6/4-11 (Scheme 6/4.3). 

The oxepine-fused beta-carboline 73 was synthesized in good yield (71%) from the diene precursor 72 using ring-closing metathesis and Grubbs I catalyst <06TL6895>. 

In 2003, Efskind and Undheim reported dienyne and triyne domino RCMs of appropriately functionalized substrates with Grubbs type II or I catalysts (Scheme 6.71, reactions a and b, respectively) [151]. While the thermal processes (toluene, 85 °C) required multiple addition of fresh catalyst (3 x 10 mol%) over a period of 9 h to furnish a 92% yield of product, microwave irradiation for 10 min at 160 °C (5 mol% catalyst, toluene) led to full conversion. The authors ascribe the dramatic rate enhancement to rapid and uniform heating of the reaction mixture and increased catalyst lifetime through the elimination of wall effects. In some instances, use of the Grubbs I catalyst was more efficient than use of the more common Grubbs II equivalent. 

N-Boc-N-(but-2-enoyl)amine is an excellent pronucleophile for the Ir-catalyzed allylic amination under salt-free conditions (cf. Table 9.3, entries 15-18). The products were subjected to RCM with good results, even upon application of the Grubbs I catalyst (Scheme 9.29) [27bj. The resultant N-Boc protected a,P-unsaturated y-lactams are valuable chiral intermediates with appUcations in natural products synthesis and medicinal chemistry. 

Ir-catalyzed alkylation with a nitro compound was applied in a synthesis of flS,2R)-tra s-2-phenylcyclopentanamine, a compound with antidepressant activity (Scheme 9.41) [45]. The reaction of cinnamyl methyl carbonate with 4-nitro-l-butene gave the substitution product with 93% ee in 82% yield. A Grubbs I catalyst sufficed for the subsequent RCM. Further epimerization with NEts yielded a trans-cyclopentene in 83% yield via the two steps, while additional reduction steps proceeded in 90% yield. 

RCM to afford compound 21 (Scheme 6). Although Grubbs II catalyst afforded compound in moderate yield (64%), only the dimerization product could be obtained using Grubbs I catalyst (10 mol% Grubbs I, PhMe, reflux, 16 h, 37% of dimerization product of 21, 6% of expected product 21). 

In a further application of a ring-closing metathesis, the preparation of the syn- and A -azepinones 169 and 170, respectively, was achieved from the hydrochloride salt of the precursor 168 using Grubbs I catalyst (Equation 19). The jy -isomer 169 showed particularly strong (subnanomolar) in vitro binding to the K-opioid receptor <2004BML5693>. 

A neat alternative approach to spiro-azepinones involved a ring-closing metathesis of 198 to give 199 in good yields using Grubbs I catalyst (Equation 25) <2002SL1827>. 

The Pd-catalyzed reaction of 211 with allyltributyltin to give 212, followed by N-alkylation to 213, afforded the 1-benzazepine derivative 214 in high yield on Ru-catalyzed ring-closing metathesis with Grubbs I catalyst 159 (Scheme 28) <2005JOC1545>. 

The ring-closing metathesis reaction has also been applied to the formation of a seven-membered cyclic sulfonamide C1999TL4761 >. Thus, heating 27 at reflux in dichloromethane (DCM) with ruthenium catalysis (Grubbs I catalyst) gave 28 in high yield (Equation 5). 

Classical ring closures (of the FriedelCrafts, Dieckmann, etc., types) can be applied to benzazepine synthesis <1974AHC(17)45>. Particularly useful are approaches to benzazepines based on transition metal-catalyzed cyclizations , as illustrated by the synthesis of 1-benzazepine derivative 149 in high yield by Ru-catalyzed ring-closing metathesis with Grubbs I catalyst (Scheme 87) <2005JOC1545>. 

The modified Grubbs I catalyst 18 is effective for RCM of functionalized dienes and... 

Sequential Heck reaction and hydrosilylation of carbonyl have been carried out with the Grubbs I catalyst. AUyUc alcohols can be S3mthesized via conjugated carbonyl compounds prepared from cross-metathesis in situ by reduction with j-Bu2AlH. An access to enantiomeric 2,3-dihydroxyalkanoic esters is based on cross-metathesis, dihydroxylation and methanolysis. ... 

From these studies, it was demonstrated that the alkene metathesis activity was not due to the allenylidene precursor, but due to the indenylidene ruthenium catalyst 6, which has a structure analogous to the Grubbs I catalyst [15, 17]. Both complexes generate the same RuCl2(=CFl2) intermediate upon reaction with a terminal alkene. 

Ru-carbene Grubbs I catalyst did not polymerize 5-trimethylsilylnorbomene in a living manner (/p 1, Table 2). At the same time, it was shown that the presence of functionalized substituents in monomer molecule is able to coordinate the catalyst, decrease to some extent its activity, and lead a living process [156]. Thus, block-copolymers of 5-(dicarbazolylmethylsilyl)norbomene and 5-(trimethylsilyloxymethyl)norbomene (NBCHaOSiMes) were obtained by living polymerization in the presence of Grubbs 1 complex [190]. 

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