Dienes cyclization-hydrosilylation

Yttrium-catalyzed diene cyclization/hydrosilylation was applied to the synthesis of aliphatic nitrogen heterocycles such as the indolizidine alkaloid ( )-epilupinine. l-Allyl-2-vinylpiperidine 30 was synthesized in four steps in 59% overall yield from commercially available ( )-2-piperidinemethanol (Scheme 10). Treatment of 30 with phenylsilane and a catalytic amount of Gp 2YGH3(THF) gave silylated quinolizidine derivative 31 in 84% yield, resulting from selective hydrometallation of the A-allyl G=G bond in preference to the exocyclic vinylic G=G bond. Oxidation of the crude reaction mixture with tert-huVf hydrogen peroxide and potassium hydride gave (i)-epilupinine in 51-62% yield from 30 (Scheme 10). 

Palladium-catalyzed diene cyclization/hydrosilylation was compatible with a number of functionalized silanes, including dimethylphenylsilane, dimethylbenzylsilane, dimethylbenzhydrylsilane, and pentamethyldisiloxane... 

Palladium-catalyzed asymmetric cyclization/hydrosilylation tolerated a number of functional groups including benzyl and pivaloyl ethers as well as benzyl and methyl esters (Table 8, entries 1-4). Furthermore, the protocol tolerated substitution at one of the two /ra/zi -terminal alkenyl positions and at one of the two allylic positions of the 1,6-diene (Table 8). As was the case with diene cyclization/hydrosilylation catalyzed by achiral palladium... 

Hydrosilylation of dienes accompanied by cyclization is emerging as a potential route to the synthesis of functionalized carbocycles. However, the utility of cycliza-tion/hydrosilylation has been Umited because of the absence of an asymmetric protocol. One example of asymmetric cycUzation/hydrosilylation has been reported very recently using a chiral pyridine-oxazoUne ligand instead of 1,10-phenanthroline of the cationic palladium complex (53) [60]. As shown in Scheme 3-21, the pyridine-oxazoUne Ugand is more effective than the bisoxazoUne ligand in this asymmetric cyclization/hydrosilylation of a 1,6-diene. 

The rhodium-catalyzed cyclization/hydrosilylation of internal diyne proceeds efficiently with high stereoselectivity (Scheme 106). However, terminal diynes show low reactivity to rhodium cationic complexes. Tolerance of functionalities seems to be equivalent between the rhodium and platinum catalysts. The bulkiness of the hydrosilane used is very important for the regioselectivity of the rhodium-catalyzed cyclization/hydrosilylation. For example, less-hindered dimethylethylsilane gives disilylated diene without cyclization (resulting in the double hydrosilylation of the two alkynes), and /-butyldimethylsilane leads to the formation of cyclotrimerization compound. 

Hydrosilylation of 1,6-dienes accompanied by cyclization giving a five-membered ring system is emerging as a potential route to the synthesis of functionalized carbocycles.81,81a,81b 82 As its asymmetric version, diallylmalonates 86 were treated with trialkylsilane in the presence of a cationic palladium catalyst 88, which is coordinated with a chiral pyridine-oxazoline ligand. As the cyclization-hydrosilylation products, //ww-disubstituted cyclopentanes 87 were obtained with high diastereoselectivity (>95%), whose enantioselectivity ranged between 87% and 90% (Scheme 25).83 83a... 

For the conversion of silyl-carbon bond in the cyclization products into hydroxy-carbon bond, several functionalized hydrosilanes were examined (Scheme 27).84,84a,84b Of the hydrosilanes examined, benzhydryldimethylsilane (HSiMe2CHPh2) was found to be most enantioselective in the reaction of diene 86a to give the cyclization product 87a with 93% ee. The second highest enantioselectivity (91% ee) was observed with hydrosiloxane HSiMe2OSiPh2Bu-/. The cyclization-hydrosilylation with the HSiMe2CHPh2 and catalyst 88 was very successful... 

The asymmetric cyclization-hydrosilylation of 1,5-dienes has been also reported by use of a chiral yttrocene complex (Scheme 32).87 Highest enantioselectivity (50% ee) was observed for 3,3-dimethyl-l,5-hexadiene with diphenylsilane. 

Yamamoto has proposed a mechanism for the palladium-catalyzed cyclization/hydrosilylation of enynes that accounts for the selective delivery of the silane to the more substituted C=C bond. Initial conversion of [(77 -C3H5)Pd(GOD)] [PF6] to a cationic palladium hydride species followed by complexation of the diyne could form the cationic diynylpalladium hydride intermediate Ib (Scheme 2). Hydrometallation of the less-substituted alkyne would form the palladium alkenyl alkyne complex Ilb that could undergo intramolecular carbometallation to form the palladium dienyl complex Illb. Silylative cleavage of the Pd-G bond, perhaps via cr-bond metathesis, would then release the silylated diene with regeneration of a palladium hydride species (Scheme 2). 

Gyclization/hydrosilylation of enynes catalyzed by rhodium carbonyl complexes tolerated a number of functional groups, including acetate esters, benzyl ethers, acetals, tosylamides, and allyl- and benzylamines (Table 3, entries 6-14). The reaction of diallyl-2-propynylamine is noteworthy as this transformation displayed high selectivity for cyclization of the enyne moiety rather than the diene moiety (Table 3, entry 9). Rhodium-catalyzed enyne cyclization/hydrosilylation tolerated substitution at the alkyne carbon (Table 3, entry 5) and, in some cases, at both the allylic and terminal alkenyl carbon atoms (Equation (7)). 

Cyclization/Hydrosilylation of Dienes 11.11.4.1 Lanthanide Metallocene Catalysts... 

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)). 

Cyclization/hydrosilylation catalyzed by Cp 2YCH(SiMe3)2 failed in the case of dienes that possessed substitution on the alkenyl carbon atoms, presumably due to the excessive steric crowding about the yttrium center. In contrast. 

Bercaw has investigated the application of the 6 2-symmetric, enantiomerically pure lanthanide metallocene derivative (i ,A)-BnBpYH 34 as a catalyst for the asymmetric cyclization/hydrosilylation of 1,5- and 1,6-dienes. Although 34 displayed high activity for the reaction of a number of dienes, asymmetric induction was low. In the best case, reaction of 3,3-dimethyl-1,5-hexadiene with phenylsilane catalyzed by 34 gave silylated cyclopentene 35 in 95% yield with 50% ee (Equation (25)). 

Table 6 Palladium-catalyzed cyclization/hydrosilylation of functionalized 1,6-dienes...

Widenhoefer and co-workers have developed an effective Pd-catalyzed protocol for the asymmetric cyclization/ hydrosilylation of functionalized 1,6-dienes that employed chiral, non-racemic pyridine-oxazoline ligands." " " Optimization studies probed the effect of both the G(4) substituent of the pyridine-oxazoline ligand (Table 7, entries 1-6) and the nature of the silane (Table 7, entries 6-15) on the yield and enantioselectivity of the cyclization/ hydrosilylation of dimethyl diallylmalonate. These studies revealed that employment of isopropyl-substituted catalyst (N-N)Pd(Me)Gl [N-N = (i )-( )-4-isopropyl-2-(2-pyridinyl)-2-oxazoline] [(i )-43f and a stoichiometric amount of benzhydryldimethylsilane provided the best combination of asymmetric induction and chemical yield, giving the corresponding silylated cyclopentane in 98% yield as a single diastereomer with 93% ee (Table 7, entry 15). 

Table 8 Asymmetric cyclization/hydrosilylation of functionalized dienes catalyzed by (R)-43f/NaBAr4...

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. 

Cyclization—distannylation, bis(l,3-dienes), 11, 408 cyclization—hydrogermylation, 1,6-Dienes, 11, 408 Cyclization-hydrosilylation asymmetric, example, 10, 833 cascade, trienes, 11, 395 dienes, 11, 379 diynes... 

As an extension of hydrosilylation of alkenes, cyclization-hydrosilylation of 1,6-dienes occurs by the reaction with HSiRs [23]. The cationic complex 37, generated in situ from (phen)Pd(Me)Cl and NaBAr4, is an active catalyst, catalyzing the reaction of dimethyl diallylmalonate (36) with HSiCl3 to give the disubstituted cyclopentane 38 with 98% trans selectivity in 92% yield [24]. A mechanism different from that of usual hydrosilylation, which postulates formation of H-Pd-SiR3 and hydropalladation of alkene, was proposed by Widenhoefer... 

R. A. Widenhoefer developed a mechanistic study on the cyclization-hydrosilylation of various functionalized dienes catalyzed by cationic palladium phenanthroline or oxazoline complex (60). Kinetic, deuterium-labeling, and low temperature nuclear magnetic resonance studies permitted establishing a... 

Functionalized 1,6-dienes in the presence of stoichiometric amounts of triethylsilane undergo palladium-catalyzed cyclization-hydrosilylation to form (silyl)methyl-substituted cyclopentanes (195). l-Buten-3-ynes, in the presence of palladium monoferrocenylmonophosphine, or bis(ferrocenyl)monophosphine, undergo asymmetric 1,4-hydrosilylation with trichlorosilane to give axially... 

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