Cyclization of 1,5- and 1,6-dienes

Among early and group III transition metals, the yttrocene catalysts have been studied in greatest detail. However, related metallocenes show great promise as catalysts for reductive cyclization. Neodymocene-catalyzed cyclization of 1,5- and 1,6-dienes 14a and 15a proceeds readily in the presence of silane to afford cyclopentanes 14b and 15b.37 Lutetocenes and samarocenes also catalyze silane-mediated cyclization of 1,5-diene 14a to cyclopentane 14b.38 39 In the case of the samarium-based metallocenes, the feasibility of borane-mediated cyclization has been established, as demonstrated by the highly diastereoselective conversion of phenyl-substituted diene 16a to cyclopentane 16b (Scheme ll).40... 

The use of organotyrium catalysts in reductive cyclization of 1,5- and 1,6-dienes has been reported the yields are in the range of 53-99%. The catalytic species is generated in situ by reduction of Cp2 YMe503. 

Functionalities such as ether and acetals have been tolerated in an organo-yttrium-catalyzed cyclization of 1,5- and 1,6-dienes [100]. The precatalyst 4(Y Me)/THF could be easily prepared by a one-pot reaction. The enormous effect of bulky groups R in the 3-position of an 1,5-diene on the regio- and diastereos-electivites is in agreement with the debated mechanism (eq. (7)). Under the prevailing reaction conditions (H2 ) cyclization of 1,6-dienes is complicated by hydrogenation reactions. 

Cyclization of 1,5- and 1,6-dienes.2 Treatment of 1 with hydrogen generates Cp2YH (2) with release of CH4. This hydride is an effective catalyst for cyclization of 1,5- and 1,6-dicncs, even those with bulky substituents. No cyclization is observed when the substrate bears CN, COOCH, or S02C6H5 groups. 

One example of asymmetric diene silylation was reported using the binaphthalenediol-based yttrocene catalyst (Fig. 3) [49]. A variety of 1,5- and 1,6-dienes were cyclized in 70-95% yields, but with < 5-50% ees. Due to the slower cyclization of 1,6-diene substrates, PhMeSiH2 was in place of PhSiH3 to prevent hydrosilylation of the olefins. 

To date, a single study pertaining to enantioselective yttrocene-catalyzed reductive diene cyclization is reported.36 Using the -symmetric yttrocene [(R,Y)-BnBpY-H]2, a range of 1,5- and 1,6-dienes are transformed to the corresponding cyclopentanes and cyclohexanes. In terms of asymmetric induction, the formation of cyclopentane 13b in 50% ee from 1,5-diene 13a represents the most favorable result (Scheme 10). 

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)). 

Scheme 11. Organoyttrium-catalyzed sequential cyclization/silylation of 1,5- and 1,6-dienes...

Besides enyne metathesis [66] (see also the chapter Recent Advances in Alkenes Metathesis in this volume), which generally produces 1-vinylcyclo-alkenes, ruthenium-catalyzed enyne cycloisomerization can proceed by two major pathways via hydrometallation or a ruthenacycle intermediate. The RuClH(CO)(PPh3)3 complex catalyzed the cyclization of 1,5- and 1,6-enynes with an electron-withdrawing group on the alkene to give cyclized 1,3-dienes, dialkylidenecyclopentanes (for n=2), or alkylidenecyclopentenes (for n= 1) [69,70] (Eq. 51). Hydroruthenation of the alkyne can give two vinylruthenium complexes which can undergo intramolecular alkene insertion into the Ru-C bond. 

Under the influence of nickel catalysts, 1,5- and 1,6-dienes undergo isomerization and cyclization, preferably to five-membered ring compounds. The cyclization takes place probably via an intramolecular insertion reaction ( , ) involving a ir-5-alken-l-ylnickel complex such as 33, Table III, and 34, Table IV formed by Ni — C, and Ni — C2 additions... 

The 1,5- and 1,6-dienes undergo a cyclization/boration reaction in the presence of a catalytic amount of Cp 2Sm(THF). The resulting organoboranes can be oxidized to the corresponding primary cyclic alcohols using standard conditions (Scheme 274).1021... 

Reaction of iodine with non-conjugated dienes has been applied to the synthesis of cyclic compounds100. Although the reactions of 1,5-hexadiene, 1,6-heptadiene and 1,7-octadiene with I2 in CCI4 gave exclusively products arising from addition to the two double bonds, the introduction of dialkyl substituents into the 4-position of 1,6-heptadiene completely changed the reaction course in favor of cyclization (equation 85). 

Grigg reported tandem radical addition/5-exo cyclization reactions of bromotri-chloromethane and 1,6-dienes 169 catalyzed by 5 mol% Ru(PPh3)3Cl2 (Fig. 42). 

Appropriately substituted triplet 1,4-biradicals can undergo direct 1,5-and 1,6-cyclization to triplet cyclopentenylcarbenes or triplet 1,2-cyclohexa-dienes, respectively (Sch. 7) [44 16]. The typical substitution pattern for such competitive reactions is the presence of a sp-hybridized C-atom linked to one... 

A characteristic transformation of nonconjugated dienes is their hydroboration to form boraheterocycles.369 For example, the favored hydroborating agent, 9-BBN, is synthesized in such cyclization reaction370,371 (Scheme 6.6). An approximately 1 3 mixture of 1,4- and 1,5-addition products is formed in a second, intramolecular hydroboration step. The 1,4-addition product (40), however, can be readily isomer-ized under mild conditions (65°C, 1 h) through a dehydroboration-hydroboration step to yield pure 9-BBN. 

Negishi, E., Ma, S., Amanfii, J., Coperet, C., Miller, (.A. and Tour, J.M. (1996) Palladiiuncarbon monoxide. Journal of the American Chemical Society, 118, 5919-5931. 

A mode] study has demonstrated the pathways shown in Scheme 4,17. The first cyclization step gave predominantly five-membered rings, the second a mixture of six- and seven-membered rings.155 Relative rate constants for the individual steps were measured. The first cyclization step was found to be some five-fold faster than for the parent 5-hexenyl system. Although originally put forward as evidence for hyperconjugation in 1,6-dienes, further work showed the rate acceleration to be sterie in origin.113-I3j... 

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. 

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)). 

Guided by Marks s report of the samarium-catalyzed hydroboration of alkenes, Molander has developed a samarium-catalyzed protocol for the cyclization/hydroboration of unfunctionalized 1,6-dienes. In an optimized procedure, reaction of 1,5-hexadiene and l,3-dimethyl-l,3-diaza-2-boracyclopentane catalyzed by Gp 2Sm(THF) in toluene at room temperature for 18 h followed by oxidation gave hydroxymethylcyclopentane in 86% yield (Equation (70) R = H, n — ). The transformation was stereoselective, and Sm-catalyzed cyclization/hydroboration of 2-phenyl-1,5-hexadiene followed by oxidation formed /ra/ i--l-hydroxymethyl-2-phenylcyclopentane in 64% yield (Equation (70) R = Ph, n = ). The samarium-catalyzed reactions was also applicable to the synthesis of hydroxymethylcyclohexanes (Equation (70), n=X) but tolerated neither polar functionality nor substitution on the alkenyl carbon atoms. 

A much more useful method for the preparation of a variety of substituted thiophenes and benzo[6]thiophenes in good yield depends on the oxidative cyclization of 1,3-diene-1-thiols (3) to the substituted thiophenes (4). This reaction was first reported (13CB1903) for the oxidation of o-mercaptocinnamic acid (5) to form benzo[6]thiophene (8) in good yield, using an aqueous alkaline solution of potassium ferricyanide. The intermediacy of a sul-fenium ion (6) was suggested, in view of the quantitative loss of carbon dioxide in the final product. 

Shibasaki and co-workers have described a regioselective Heck cyclization of aryl triflate 12.1, which ultimately provides tricyclic enone 12.4, a key intermediate in a number of diterpene syntheses (Scheme 8G.12) [25], Treatment of 12.1 under typical cationic conditions resulted in preferential 6-exo closure to give 12.2 and 12.3 as a 3 1 mixture in 62% overall yield and with 95% ee for both products. The complete selectivity for 6-exo cyclization is noteworthy because 6-endo, 5-exo, and 7-endo cyclization modes were also possible. An analysis of the steric interactions involved in the various cyclization modes was presented and was used to rationalize the observed selectivity. Non-conjugated diene 12.2 could be isomerized to the fully conjugated diene 12.3 in quantitative yield by using catalytic naphthalene Cr(CO)3. Both Heck products could be converted to the enone 12.4,... 

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