Catalytic cyclization

Another method for conducting cyclizations catalytic in Cp2TiCl is shown in Scheme 14. It relies on the thermodynamically favorable ring closure of THF from 5-titanoxy radicals [81,82]. This step is mechanistically related to the oxygen rebound steps of oxidation reactions. While the scope of this transformation remains to be established, the presence of substituted THF-derivatives in many natural products renders the method potentially attractive. 

Homoallyl chloroformates cyclize catalytically to a-methylene- y-butyrolactones in moderate yields at 130 C with tetrakis(triphenylphosphine)palladium(0) (equation 44).l0s This reaction only gives 1-2% of product when it is carried out intermolecularly. The presumed intermediate in the homoallyl chlorofor-mate cyclization has been isolated and kinetic measurements show that that cyclization is inhibited by an excess of triphenylphosphine. A chelated ir-alkene intermediate is proposed.1 6... 

Pauson and Khand discovered the very important class of alkyne/alkene/CO cyclization catalytic reactions catalyzed, once again, by Co2(CO)g see Pauson-Khand Reaction). This reaction produces a, /3-unsaturated cyclopentanones (equation 23). With unstrained alkenes the reaction works best in a stoichiometric setting, but with strained alkenes like norbomadiene the reaction can be made catalytic. These reactions have been fairly extensively studied, and the reaction proceeds through an alkyne-bridged Co2(CO)6 dimer species. Unsymmetrical alkynes lead to mixtures of the various substituted a, /3-unsaturated cyclopentanone products. 

Uses. 3-Pentenenitrile, 3PN, is used entirely by the manufacturers to make adiponitrile. -2-Pentenenitrile, 2PN, can be cyclized catalytically at high temperature to produce pyridine, a solvent and agricultural chemical intermediate. 2PN is also chlorinated to manufacture pentachloropyridine, an intermediate in the insecticide Dursban produced by Dow. Addition of ammonia to 2PN followed by reduction leads to 1,3-pentadiamine (Dytek ep), which is used as a curing agent for epoxy coatings and as a chain modifier in polyurethanes. 

A variety of bisoxazolinato rare-earth metal complexes such as 30 have been studied with regard to their hydroamination/cyclization catalytic activity [149]. The precatalysts show similar enantioselectivity and only slightly reduced catalytic activity when prepared in situ from [La N(SiMe3)2 3] and the bisoxazoline ligand. In this ligand accelerated catalyst system the highest rates were observed for a 1 1 metal to ligand ratio. 

Treatment of the carbonate 379 with potassium hydride induces cyclization of the resulting j -keto enolate with the oxygen at C-6 (path b, Scheme 50), thus forming the diastereomeric product 382 as a result of inversion of configuration during the cyclization. Catalytic reduction provides the remaining stereocenters, and gives 383 as the major product (88 9 3). 

Much like the initial investigations into intramolecular oxidative Heck reactions utilizing stoichiometric palladium salts, much of the early work toward catalytic variants focused on cyclizations of anilinoquinones (Scheme 9.18) [37e, 47]. Knolker and O Sullivan [37e] reported the first example of an intramolecular oxidative Heck cyclization catalytic in... 

After separation by preparative GC, (162 a) was treated with osmium tetroxide and acid to afford brevicomin. Catalytic dimerization and carbonylation of butadiene by Byrom et al. (121), followed by reduction, epoxidation, and hydrolysis gave the alkenediol (166), which was cyclized catalytically to e /o-brevicomin (Scheme 33). A stereoselective synthesis of optically active (li ,7JR)-(+)-exo-brevicomin (150) from (2S,3S)-D-(—)-tartaric acid (167) has been achieved by Mori (122) (Scheme 34). 

In the alkylative cyclization of the 1,6-enyne 372 with vinyl bromide, formation of both the five-membered ring 373 by exn mode carbopalladation and isomerization of the double bonds and the six-membered ring 374 by endo mode carbopalladation are observed[269]. Their ratio depends on the catalytic species. Also, the cyclization of the 1,6-enyne 375 with /i-bromostyrene (376) affords the endo product 377. The exo mode cyclization is commonly observed in many cases, and there are two possible mechanistic explanations for that observed in these examples. One is direct endo mode carbopalladation. The other is the exo mode carbopalladation to give 378 followed by cyclopropana-tion to form 379, and the subsequent cyclopropylcarbinyl-homoallyl rearrangement affords the six-membered ring 380. Careful determination of the E or Z structure of the double bond in the cyclized product 380 is crucial for the mechanistic discussion. 

Induction of Asymmetry by Amino Acids. No fewer than sis types of reactions can be carried out with yields of 75—100% usiag amino acid catalysts, ie, catalytic hydrogenation, iatramolecular aldol cyclizations, cyanhydrin synthesis, alkylation of carbonyl compounds, hydrosdylation, and epoxidations (91). 

Reaction of (T)-(-)-2-acetoxysuccinyl chloride (78), prepared from (5)-mahc acid, using the magnesiobromide salt of monomethyl malonate afforded the dioxosuberate (79) which was cyclized with magnesium carbonate to a 4 1 mixture of cyclopentenone (80) and the 5-acetoxy isomer. Catalytic hydrogenation of (80) gave (81) having the thermodynamically favored aH-trans stereochemistry. Ketone reduction and hydrolysis produced the bicycHc lactone acid (82) which was converted to the Corey aldehyde equivalent (83). A number of other approaches have been described (108). 

Myrcene with its conjugated diene system readily undergoes Diels-Alder reactions with a number of dienophiles. For example, reaction with 3-meth.5i-3-pentene-2-one with a catalytic amount of AlCl gives an intermediate monocyclic ketone, which when cyclized with 85% phosphoric acid produces the bicycHc ketone known as Iso E Super [54464-57-2] (49). The product is useful in providing sandalwood-like and cedarwood-like fragrance ingredients (91). 

AH (A)-menthol is made by synthetic methods. One method involves the cyclization of (+)-citroneIlal (68). Using a mild acid catalyst, (+)-citroneIlal [2385-77-5] undergoes an ene-reaction to produce a mixture of isopulegols (142). Catalytic hydrogenation of the isopulegol mixture gives a mixture of menthol and its isomers. The (A)-menthol is obtained after efficient fractional distillation and the remaining isomers can be equilibrated, usually with sodium menthol ate or aluminum isopropoxide. An equilibrium mixture is obtained, comprised of 62 wt % (A)-menthol, 23 wt % (+)-neomenthol, 12 wt % (+)-isomenthol, and 3 wt % (+)-neoisomenthol. The equilibrium mixture can be distilled to recover additional (+)-mentbol. 

There are reports of an increasing number of palladium-assisted reactions, in some of which the palladium has a catalytic function. Thus furan and thiophene undergo facile palladium-assisted alkenylation giving 2-substituted products. Benzo[6 Jfuran and TV- acetyl-indole yield cyclization products, dibenzofurans and carbazoles respectively, in addition to alkenylated products (8UOC851). The arylation of pyrroles can be effected by treatment with palladium acetate and an arene (Scheme 86) (81CC254). 

R H) then the palladium intermediate can be induced to undergo a variety of other reactions 80JA3583). The catalytic cyclization of 5-tosylamidoalkenes to dihydropyrroles has been achieved similarly (Scheme 7b) 82JA2444). 

Aniline 77 was converted into its diazonium salt with nitrous acid and this was followed by reduction with stannous chloride to afford the corresponding arylhydrazine 78. Condensation of 78 with 3-cyanopropanal dimethylacetal 79 gave the arylhydrazone 80. Treatment of 80 with PPE resulted in cyclization to indole 81. The nitrile group was then reduced to the primary amine by catalytic hydrogenation. Reaction of the amine with excess formalin and sodium borohydride resulted in Imitrex (82). 

A variety of 2,5-dialkylfurans are available via the Paal-Knorr condensation cyclization is possible for both hindered and unhindered 1,4-diketones. Fleming prepared 2-cyclohexyl-5-methylfuran (31) in 91% yield via treatment of dione 30 with catalytic p-toluenesulfonic acid in refluxing benzene. Using the same methodology, Denisenko synthesized furan 33 in 35% yield from the corresponding dione (32). ... 

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