Heteroatom cyclopentene annulation. Synthesis of guaiane ring system

Hudlický, Tomáš; Govindan, Serengulam V.; Frazier, James O.

doi:10.1021/jo00221a043

Cited by 33 publications

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“…Ozonolysis of these dienes followed by reductive workup then yielded a mixture of the dicarbonyl products and their methanol acetals [2]. Treatment of each mixture with 3% aqueous perchloric acid in tetrahydrofuran (1:1 v/v) [10] gave the required nitro dicarbonyl substrates. The results of our reductive cyclization studies are shown in Scheme 2 [11].…”

Section: Resultsmentioning

confidence: 99%

Catalyst and pressure dependent reductive cyclizations for the diastereo‐selective synthesis of hexahydropyrrolo[1,2‐a]quinoline‐5‐carboxylic esters

Bunce

Schammerhorn

Slaughter

2006

Journal of Heterocyclic Chem

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A diastereoselective synthesis of 1,2,3,3a,4,5-hexahydropyrrolo[1,2-a]quinoline-5-carboxylic esters has been developed using a tandem reduction-double reductive amination reaction. The nitro dicarbonyl cyclization substrates were synthesized by alkylation of methyl (2-nitrophenyl)acetate with 2-bromomethyl-1,5-hexadiene derivatives, followed by ozonolysis. Catalytic hydrogenation of each substrate gave the target heterocycle, along with a deacylated product and an adduct resulting from capture of the intermediate hydroxylamine by the side chain carbonyls. The product ratio varied dramatically with the catalyst and the hydrogen pressure. Cyclization to the title compounds was highly diastereoselective, producing each hexahydropyrrolo[1,2-a]-quinoline as a single stereoisomer with the all-cis geometry. The competing processes have not been observed in previous heterocyclization studies but can be attributed to greater strain in the system, which slows the final ring closure.

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Section: Resultsmentioning

confidence: 99%

Catalyst and pressure dependent reductive cyclizations for the diastereo‐selective synthesis of hexahydropyrrolo[1,2‐a]quinoline‐5‐carboxylic esters

Bunce

Schammerhorn

Slaughter

2006

Journal of Heterocyclic Chem

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“…Prior to reductive cyclization, this mixture was treated with 3% perchloric acid:tetrahydrofuran (1:1) at 0°for 1 hour and at room temperature for 12 hours, then extracted (two times) with dichloromethane [12]. The organic layer was washed with sodium bicarbonate and sodium chloride, dried (magnesium sulfate), and concentrated under vacuum to give 970 mg (5.71 mmole, 96%) of 4c as a light yellow oil; ir: 2830, 2722, 1721 cm -1 ; 1 H nmr: δ 9.76 (t, 1H, J = 1.4), 2.47 (m, 2H), 2.38 (t, 2H, J = 7.4), 1.90 (quintet, 2H, J = 7.1), 1.65 (m, 1H), 1.57 (quintet, 2H, J = 7.4), 1.28 (m, 5H), 0.89 (t, 3H, J = 7.1); 13 C nmr: δ 210.…”

Section: Jan-feb 2003 117mentioning

confidence: 99%

“…Since trace amounts of acid produced in the ozonolyses led to the formation of cyclic peroxides from the alkyl 3-butenyl ketones [11], reactions of 1a-i were performed in the presence of catalytic sodium bicarbonate [9a] and the crude ozonolysates were used directly in the hydrogenation. The ozonolyses of 3a-i, 5a-c and 7a-b to prepare 5-oxoaldehydes were less susceptible to cyclization and were carried out using our previously described procedure [7,12].…”

Section: Introductionmentioning

confidence: 99%

“…These compounds were more easily purified and stored than the dicarbonyl compounds. Prior to reductive cyclization, treatment of each keto acetal with 3% perchloric acid:tetrahydrofuran (1:1) regenerated the 5-oxoaldehyde [7,12]. Reaction of these keto aldehydes with 2 equivalents of nitrobenzene under catalytic hydrogenation conditions then afforded the piperidine derivatives.…”

Section: Introductionmentioning

confidence: 99%

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N‐Phenyl‐Substituted Pyrrolidines, Piperidines and Azabicyclics by a Tandem Reduction‐Double Reductive Amination Reaction.

et al. 2003

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N-Phenyl-substituted pyrrolidines and piperidines have been synthesized by catalytic reduction of nitrobenzene in the presence of 4-and 5-oxoaldehydes, respectively. The process involves reduction of the aromatic nitro group to give the N-phenylhydroxylamine or aniline followed by reductive amination with the two carbonyl functional groups. Monocyclic systems are generally formed in high yield and are easily purified. The method has also been extended to the synthesis of fused N-phenylazabicyclics from 2-(3-oxopropyl)cycloalkanones. A high degree of diastereoselectivity for the trans-fused product is observed in substrates having an ester group α to the cycloalkanone carbonyl. Bicyclic precursors lacking this ester group give mixtures of cis and trans products. Finally, contrary to previous reports, we have demonstrated that aniline can be substituted for nitrobenzene in these reactions.

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“…Vacuum filtration and concentration under reduced pressure gave the dimethyl acetal 3 containing 5-10% of aldehyde 4. This mixture was dissolved in 25 mL of tetrahydrofuran, cooled to 0˚, and 25 mL of 3% aqueous perchloric acid was added dropwise with stirring [10]. The solution was stirred at 0f or 1 hour and at room temperature for 4 hours, then extracted with dichloromethane (three times).…”

Section: Introductionmentioning

confidence: 99%

Diastereoselective Synthesis of Substituted 2,3,4,5‐Tetrahydro‐1H‐1‐benzazepine‐5‐carboxylic Esters by a Tandem Reduction‐Reductive Amination Reaction.

2004

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An efficient, diastereoselective synthesis of substituted and unsubstituted 2,3,4,5-tetrahydro-1H-1-benzazepine-5-carboxylic esters has been developed based on the tandem reduction-reductive amination reaction. Catalytic hydrogenation of a series of 2-(2-nitrophenyl)-5-oxoalkanoic esters initiates a reaction sequence involving (1) reduction of the aromatic nitro group, (2) condensation of the N-hydroxylamino (or amino) nitrogen with the side chain carbonyl, and (3) reduction of the seven-membered cyclic imine. Cyclizations that produce 2-alkyl-2,3,4,5-tetrahydro-1H-1-benzazepine-5-carboxylic esters are diastereoselective for the product having the C2 alkyl and the C5 ester groups cis. In these reactions, the transannular ester group exerts a strong stereodirecting effect on the reduction of the cyclic imine intermediate, though not as strong as that observed in previous closures of 2-alkyl-1,2,3,4-tetrahydroquinoline-4-carboxylic esters. This decrease in diastereoselectivity is attributed to (1) the greater distance between the ester and the imine double bond and (2) the increased conformational mobility of the larger ring, both of which diminish the stereodirecting effect of the ester. Finally, formation of the seven-membered ring is sufficiently slow that reaction with the side chain ester group competes with heterocycle formation in several of the reactions.

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Heteroatom cyclopentene annulation. Synthesis of guaiane ring system

Abstract: The investigation of Verbesina sphaerocephala afforded an amorphane 7-lactol; the structure was established by interpretation of spectral data and X-ray diffraction analysis.

Cited by 33 publications

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Catalyst and pressure dependent reductive cyclizations for the diastereo‐selective synthesis of hexahydropyrrolo[1,2‐a]quinoline‐5‐carboxylic esters

Catalyst and pressure dependent reductive cyclizations for the diastereo‐selective synthesis of hexahydropyrrolo[1,2‐a]quinoline‐5‐carboxylic esters

N‐Phenyl‐Substituted Pyrrolidines, Piperidines and Azabicyclics by a Tandem Reduction‐Double Reductive Amination Reaction.

Diastereoselective Synthesis of Substituted 2,3,4,5‐Tetrahydro‐1H‐1‐benzazepine‐5‐carboxylic Esters by a Tandem Reduction‐Reductive Amination Reaction.

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