Intramolecular cyclization nickel-catalyzed

C-C bond formation mediated by silane.6,6a 6f With respect to the development of intramolecular variants, these seminal studies lay fallow until 1990, at which point the palladium- and nickel-catalyzed reductive cyclization of tethered 1,3-dienes mediated by silane was disclosed. As demonstrated by the hydrosilylation-cyclization of 1,3,8,10-tetraene 21a, the /rarcr-divinylcyclopentanes 21b and 21c are produced in excellent yield, but with modest stereoselectivity.46 Bu3SnH was shown to participate in an analogous cyclization.46 Isotopic labeling and crossover experiments provide evidence against a mechanism involving initial diene hydrosilylation. Rather, the collective data corroborate a mechanism involving oxidative coupling of the diene followed by silane activation (Scheme 15). 

Among early reported Pd-catalyzed reactions, the Mori-Ban indole synthesis has proven to be very useful for pyrrole annulation. In 1977, based on their success of nickel-catalyzed indole synthesis from 2-chloro-fV-allylaniline, the group led by Mori and Ban disclosed Pd-catalyzed intramolecular reactions of aryl halides with pendant olefins [122]. Compound 102, easily prepared from 2-bromo-lV-acetylaniline and methyl bromocrotonate, was adopted as the cyclization precursor. Treatment of 102 with Pd(OAc)2 (2 mol%), Ph3P (4 mol%) and NaHCQ3... 

Tamao and Ito proposed a mechanism for the nickel-catalyzed cyclization/hydrosilylation of 1,7-diynes initiated by oxidative addition of the silane to an Ni(0) species to form an Ni(ii) silyl hydride complex. Gomplexation of the diyne could then form the nickel(ii) diyne complex la (Scheme 1). Silylmetallation of the less-substituted G=C bond of la, followed by intramolecular / -migratory insertion of the coordinated G=G bond into the Ni-G bond of alkenyl alkyne intermediate Ila, could form dienylnickel hydride intermediate Ilia. Sequential G-H reductive elimination and Si-H oxidative addition would release the silylated dialkylidene cyclohexane and regenerate the silylnickel hydride catalyst (Scheme 1). 

Diyne cyclization/hydrosilylation catalyzed by 4 was proposed to occur via a mechanism analogous to that proposed for nickel-catalyzed diyne cyclization/hydrosilylation (Scheme 4). It was worth noting that experimental evidence pointed to a silane-promoted reductive elimination pathway. In particular, reaction of dimethyl dipropargylmalonate with HSiMc2Et (3 equiv.) catalyzed by 4 led to predominant formation of the disilylated uncyclized compound 5 in 51% yield, whereas slow addition of HSiMe2Et to a mixture of the diyne and 4 led to predominant formation of silylated 1,2-dialkylidene cyclopentane 6 (Scheme 5). This and related observations were consistent with a mechanism involving silane-promoted G-H reductive elimination from alkenylrhodium hydride species Id to form silylated uncyclized products in competition with intramolecular carbometallation of Id to form cyclization/hydrosilylation products (Scheme 4). Silane-promoted reductive elimination could occur either via an oxidative addition/reductive elimination sequence involving an Rh(v) intermediate, or via a cr-bond metathesis pathway. 

Mori has reported the nickel-catalyzed cyclization/hydrosilylation of dienals to form protected alkenylcycloalk-anols." For example, reaction of 4-benzyloxymethyl-5,7-octadienal 48a and triethylsilane catalyzed by a 1 2 mixture of Ni(GOD)2 and PPhs in toluene at room temperature gave the silyloxycyclopentane 49a in 70% yield with exclusive formation of the m,//7 //i -diastereomer (Scheme 14). In a similar manner, the 6,8-nonadienal 48b underwent nickel-catalyzed reaction to form silyloxycyclohexane 49b in 71% yield with exclusive formation of the // /i ,// /i -diastereomer, and the 7,9-decadienal 48c underwent reaction to form silyloxycycloheptane 49c in 66% yield with undetermined stereochemistry (Scheme 14). On the basis of related stoichiometric experiments, Mori proposed a mechanism for the nickel-catalyzed cyclization/hydrosilylation of dienals involving initial insertion of the diene moiety into the Ni-H bond of a silylnickel hydride complex to form the (7r-allyl)nickel silyl complex li (Scheme 15). Intramolecular carbometallation followed by O-Si reductive elimination and H-Si oxidative addition would release the silyloxycycloalkane with regeneration of the active silylnickel hydride catalyst. 

Diamination of alkenes can also be achieved intramolecularly through the nickel-catalyzed oxidation reaction, affording a wide-range of different cyclic sulfamides <07AG(E)7125>. The cyclization of sulfamide 223 proceeds in the presence of NiCU or Ni(acac)2 (10 mol%) and PhI(OAc)2 with complete selectivity, and no products other than cyclic sulfamides are observed. An initial involvement of aminometalation generates a cyclic intermediate 224. The subsequent oxidative C-N bond formation, presumably via a Ni(III) intermediate from oxidation with PhI(OAc)2, yields the bicyclic sulfamide 225. The reaction scope is well extended to the formation of spiro-cyclic sulfamides, tricyclic sulfamides and chiral substrates... 

Enchaining radical cyclizations steps to provide polycyclic compounds is the simplest approach. Because the 5-exo cychzation is the most straightforward mode of cychzation, polyquinanes have been the object of many studies [20]. Roimd-trip strategies as defined by Haney and Curran [21], from a vinyl radical such as 8 have been developed by Takasu et al. [22] and revisited by Tripp et al. (Scheme 3) [23]. Mixtures of diastereomers 9 are obtained from hnear precursor 7. The same group has examined the intramolecular addition of a vinyl radical onto a dienoate to produce [4 -l-1]- or [4 + 2]-annulated compounds [24]. Tandem 5-exo-trig cyclizations have also been shown to yield tricyclo[6.2.1.0 ]undecan-4-one and related polycyclic compounds, using a nickel-catalyzed electroreduction [25]. 

Several other examples of stereoselective synthesis of polycyclic ketones, via carbonylative [2 + 2 + 1] cycloaddition of organopalladium compounds derived from norbornene and norbor-nadiene, have been reported53,54,121. These reactions are useful in the synthesis of cyclopen-tanoid compounds, such as dihydrojasmone54 The nickel-catalyzed version of this method was used in a total synthesis of methylenomycin B55 and in the stereoselective synthesis of bicy-clo[3.3.0]oct-l-en-3-one derivatives56. Thus, (E)- or (Z)-9-bromo-l-methoxy-7-nonen-2-yne (5), upon intramolecular carbonylative cyclization promoted by tetracarbonyl nickel, afford the same stereoisomer of methyl 1,2,4,5.6,6a-hexahydro-3-methoxymethyl-2-oxo-l-pentaleneac-etate (6) in 43-50% yield with a relative trans configuration of the H-l and H-6a protons. 

In a closely related palladium- or nickel-catalyzed reaction, diene halides, acetates or carbonates 12 can be cyclized via intramolecular metallo-ene reaction of the allylpalladium intermediates. Various subsequent reactions can follow, such as dehydropalladation59 64-122 or car-boxylation and further carbonylativc cyclization to bicyclic products60 65 67. Dicarborative addition reactions of the latter type and their synthetic use have been extensively reviewed 68-69. 

A nickel-catalyzed ene cyclization (sec. 11.13) has been reported that uses Ni(cod)2- The reaction proceeds by initial formation of a ac-allylnickel complex, which facilitates the intramolecular ene reaction with an allylic amine unit. l jt-Allylnickel complexes can be used in coupling reactions with both aryl and alkyl halides. Enolate anions react with nickel(O) reagents to form a complex that subsequently couples to aryl iodides. Semmelhack s final step in the synthesis of cephalotaxinone (446) treated 445 with Ni(cod)2 to... 

The Ma group in 2014 reported a 15 step total synthesis of aspidophylline A (8) in racemic form, that featured the combination of a chelation-controlled intramolecular oxidative union with a late stage nickel-catalyzed cyclization... 

Ni-Catalyzed Reactions The nickel-catalyzed cross-coupling of alkenyl Grignard reagents with aryl nitrile derivatives has been exploited by Miller and coworkers [4]. The conditions are similar to those described in Scheme 22.2. In general, alkenyl Grignards were /Zmixtures and therefore provided styrene derivatives as a mixture of E and Z isomers in modest to good yields (43-80%). Milder conditions were later developed in the Ni-catalyzed arylcyanation of alkynes, in which the insertion of alkynes into an aromatic C-CN bond took place (Scheme 22.12a) [5, 21a, b]. The intramolecular version of the reaction was likewise reported, and cyclization in a 5-exo-dig fashion occurred (Scheme 22.12b) [21c]. The addition of Lewis acids, such as AlMe Cl, AlMe, and... 

Additionally, several nickel-catalyzed systems for pyridines synthesis have also been developed by Louie and coworkers. In 2005, they reported that with Ni(COD)2 as the catalyst and carbene as the ligand, the cyclization can be carried out at room temperature (Scheme 3.23a) [51]. Both intramolecular and intermolecular reactions were proceeded well and the cycloaddition of an asymmetrical diyne afforded a single pyridine regioisomer. This catalytic system was extended to cyanamides as well [52], In their systematic studies, they found the in situ formed dimeric [Ni(IPr)RCN]2 from the reaction of Ni(COD)2, IPr, and nitrile are catalytically competent in the formation of pyridines from the cycloaddition of diynes and nitriles. X-ray analysis revealed that these species display simultaneous f- and 17 -nitrile binding modes. Kinetic... 

Directed orf/to-metalation (DoM) chemistry [81] further reinforces the versatility of nickel-catalyzed C-O bond activation reactions. Based on the strong accelerating and orf/to-directing effect of carbamate functionality in the base-induced deprotonation of arenes, an array of electrophiles can be introduced at the ortho position of aryl carbamates. For instance, DoM of dicarbamate, followed by 1,2-addition to a,(3-unsaturated aldehyde and intramolecular cyclization, furnishes the 2//-chromene derivative (Scheme 8) [82]. The carbamate director can finally be arylated under a nickel-catalyzed Suzuki-Miyaura-type reaction [47]. 

The same type of bis-functionalization has been reported for the palladium-catalyzed borylstannylative carbocy-cyclization of 1,6-, 1,5-, 1,7-diynes, bis-propargylamine, and ether.377 It should be noted that even 1,2-dialkylidene cyclobutane can be obtained in reasonable yield. Ito has proposed the related silaborative reaction involving nickel(O) catalysis.378 This reaction has been performed in an intra- and intermolecular fashion. The intramolecular reaction allows the formation of cyclic dienes and the intermolecular process proceeds through a dimerization of alkynes to give acyclic dienes. 

In the total synthesis of indolizomycin700, one of the key steps involved the cyclization of a thiolactam with an intramolecular a-di azoketone moiety, catalyzed by rhodium acetate (equation 195). The molecule is desulfurized by treatment with Raney nickel, giving a good yield of the required target. 

Nickel(0)-catalyzed hydrosilylation of 1,7-diynes allows intramolecular carbosilylation of one triple bond and formation of bis-alkylidene cyclohexanes with stereoselective formation of a (Z)-vinylsilane subunit60. This reaction resembles reductive cyclization of diynes catalyzed by palladium complexes (see Section 1.5.8.2.6.). 

For a few combinations of less reactive dienes and dienophiles, transition metal catalyzed variants of the Diels Alder reaction have been developed. An example is the cycloaddition of an unpolar diene and an unactivated alkyne however, except when the reaction is catalyzed with iron, nickel, cobalt, or rho-dium(I) complexes, the temperature required often causes competing decomposition, even for the intramolecular version. [2] Wilkinson s catalyst [3] - tris(triphenylphosphane)rho-dium(I) chloride - frequently used for hydrogenations and for decarbonylations, permits the cyclization of 4 to the annelated cyclo-hexadiene 5 in excellent yield in only 15 minutes at 55 °C in trifluoroethanol as solvent (Scheme 2). [2c]... 

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