1- -3-methoxy cyclization

When butadiene is treated with PdCU the l-chloromethyl-7r-allylpalladium complex 336 (X = Cl) is formed by the chloropalladation. In the presence of nucleophiles, the substituted 7r-methallylpalladium complex 336 (X = nucleophile) is formed(296-299]. In this way, the nucleophile can be introduced at the terminal carbon of conjugated diene systems. For example, a methoxy group is introduced at the terminal carbon of 3,7-dimethyl-I,3,6-octatriene to give 337 as expected, whereas myrcene (338) is converted into the tr-allyl complex 339 after the cyclization[288]. 

Vinyl ethers and a,P unsaturated carbonyl compounds cyclize in a hetero-Diels-Alder reaction when heated together in an autoclave with small amounts of hydroquinone added to inhibit polymerisation. Acrolein gives 3,4-dihydro-2-methoxy-2JT-pyran (234,235), which can easily be hydrolysed to glutaraldehyde (236) or hydrogenated to 1,5-pentanediol (237). With 2-meth5lene-l,3-dicarbonyl compounds the reaction is nearly quantitative (238). 

Cyclization. Constmction of ben2otrifluorides from aHphatic feedstocks represents a new technique with economic potential. For example, l,l,l-trichloro-2,2,2-trifluoroethane [354-58-5] and dimethyl itaconate [617-52-7] form 4-methoxy-6-trifluoromethyl-2JT-pyran-2-one [101640-70-4] which is converted to methyl 3-(trifluoromethyi)ben2oate [2557-13-3] ixh. acetjdene or norbomadiene (125). 

The Pictet-Gams method involves the cyclization of P-hydroxy- or P-methoxy- P-phenethylamides, and produces the isoquinoline derivative rather than the reduced form. A further extension of method is based on a metboxyetbyl amine. 

Methoxy 6( 2 Chlorobenzoyl)-ben2o(c acid (2).2 3-Metboxy-2(3-cblorobenzoyl)-benzolc acid 1 (1.0 g, 3.4 mmoQ was heated In cone. H2S04 (6 mL) for 1 h at 6S°C. The cooled reaction mixture was poured into ice and neutralized. The cyclized product was filtered off (0 2 g) and the filtrate was acidHIed to give 2, rrp 205°C. 

Apparently the role of methanol is to intercept unstable species which otherwise tend to polymerize or rearrange. The methoxy peroxide (72) can be isolated in crystalline form if desired, but it is preferable to treat the methylene dichloride solution at 0° with zinc dust and acetic acid until the mixture shows a negative potassium iodide test. The resulting crude seco-aldehyde (73) is then cyclized to (74) by stirring with neutral alumina in benzene at room temperature for 3 hr. ° Wechter has recently reported a number of transformations of a 5yS-hydroxy-6yS-formyl-B-norpregnane prepared in 8% yield by photolysis and hydrolysis of a 5a-hydroxy-6 -azidopregnane. 

Schopf et al. 188,189) observed that -tetrahydroanabasine salts contain a molecule of water or methanol. According to infrared spectra, they exist as 2-hydroxy- or 2-methoxy-3-(2-piperidyl)piperidine salts (97). Salt 99, obtained by a transannular cyclization reaction taking place on neutralization of bicyclic amino ketone 98, also belongs to this group 181). 

Brassard " applied the Conrad-Limpach reaction as an approach to the A-B ring system of Phomazarin. While the overall yield was only 23%, he showed that a methoxy group was an acceptable substituent on enamino-ester 46 and for the subsequent cyclization to quinolone 47. 

Evidently, the reaction proceeds via the formation of bis-adduct 289 which undergoes cyclization to dihydropyridine 290. A similar reaction with methoxybutenone, but in the presence of ammonia, which is likely to involve replacement of methoxy group, has been described (80MI2). 

The methoxy derivative 536, prepared from the aminoquinolone, was transformed into 537. Selective hydrolysis of 537 gave 538 which was treated with COCI2 followed by MeONH2 HCl to afford 539 that was cyclized upon treatment with PhI(OCOCF3)2 to give 540. Deprotection with K2CO3 afforded 541 which had central nervous system activity (95WOP9504056) (Scheme 91). 

R = Ar) and cyclized tricyclic compound 240 (R = Ar) was obtained when 2-bromoacetophenones were reacted with 8-hydroxyquinolin-2(l//)-one under the above conditions. Presence of a 4-methoxy substituent shifted the equilibrium to the ring-opened product 241 (R = 4-MeOPh), while that of 4-nitro group gave only cyclized product 240 (R = N02). Similarly, mixtures of ring-opened and 2,3,6,7-tetrahydro-5//-pyrido[l,2,3- /e]-l,4-benzoxazin-5-one derivatives were formed in the reaction of 8-hydroxy-l,2,3,4-tetrahydroquinolin-2-one and halomethyl ketones (00HCA349). 

Methoxy-5-nitrophenyl)perhydropyrido[ 1,2-a]pyrazin-3-one was obtained by cyclization of l-(ethoxycarbonylmethyl)-2-[A-(2-methoxy-5-nitrophenyl)aminomethyl]piperidine on the action of NaH in boiling dioxane (99MIP10). 

The thermal condensetion of p-benzyloxyphenylacetic acid and of 3-methoxy-4-hydroxy-phenethylamine occurs and gives, with a yield of 86% to 92%, the N-(3-methoxy4-hydroxy-phenethyl-p-benzyloxyphenylacetamide from this latter, by cyclization according to Bischler-Napieralski with phosphorus oxychloride in acetonitrile, followed by reduction with sodium borohydride, there is obtained with a yield of 75% to 80% the 1-(p-benzyloxybenzyl)-6-meth-oxy-7-hydroxy-1,2,3,4-tetrahydroisoquinoline, which is methylated with formaldehyde and formic acid giving 1 (p-benzyloxybenzyl)-2-methyl-6-methoxy-7-hydroxy-1,2,3,4-tetrahydro-isoquinoline with a yieid of 90%. 

Substituted 2-phenoxyphenylacetic acids readily cyclize under Friedel-Crafts conditions or acid catalysis to give dibenz[Z>,/]oxepin-10(l l//)-ones.71 85,104- 108 When this reaction is carried out in methanolic hydrochloric acid the 10-methoxy-substituted dibenz[6,/]oxepin system 9a can be isolated.109 5-(Nitro-2-phenoxyphenyl)-2-oxopropanoic acid undergoes cyclization in the presence of polyphosphoric acid yielding the carboxylated dibenzoxepin 9b.107... 

Benzylidenehydrazino-3-methoxyquinoxaline (273) underwent oxidative cyclization to 4-methoxy-l-phenyl[l,2,4]triazolo[4,3-fl]quinoxaline (274) [Cu(OAc)2, AcOH, reflux, 1 h 80% " tetrachlorobenzoquinone, CICH2CH2 Cl, reflux, 90 min 92% " analogs by both procedures]... 

Different approaches towards pyrazoles have been described using microwave-accelerated cyclizations. A classical approach to pyrazoles is the cyclization of a j6-diketone with hydrazines. A series of 5-trichloromethyl-pyrazoles 58 and pyrazolium chlorides 59 were synthesized by reaction of a 4-methoxy-trihalo-3-alken-one 57 with differently substituted hydrazines (Scheme 19). The use of microwave and conventional heating for making pyrazoles gave... 

The synthesis of different substituted finans by cyclization of 4-pentynones using potassium tert-butoxide in DMF was reported <96TL3387>. Dihydrofuran 32 can be prepared by a destannylative acylation of l-[(2-methoxyethoxy)methoxy]-2-(phenylsulfonyl)-2-(tributylstannyl)-cyclopropane. Treatment of 32 with BFj-EtjO yields 3-acyUurans via an intramolecular Prins-type reaction of the resulting oxonium ion intermediate <96TL4585>. 

In 2007, Womack et al. published the conversion of 2-aUcylcinnamyldehydes to 2-aLkylindanones via a catalytic intramolecular Friedel-Crafts reaction. In the presence of 5-10 mol% FeCls different in situ generated ( )-2-alkylcinnamaldehydes-derived dimethyl acetals cyclized to l-methoxy-2-aIkyl-7//-indenes in good to high yields (Scheme 6) [22]. The transformation corresponds to a formal intramolecular Friedel-Crafts acylation which is achieved with catalytic quantities of Lewis acid. This result is in strong contrast to traditional Friedel-Crafts acylations which require stoichiometric amounts of Lewis acid. 

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