Bicyclic Ketones. I. Reaction of Cyclopentadiene with cis- and trans-Benzalacetone and Acetylphenylacetylene<sup>1</sup>

Dinwiddie, J. G.; McManus, Samuel P.

doi:10.1021/jo01044a065

Cited by 5 publications

(4 citation statements)

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“…The aqueous phase was neutralized with concentrated HCl and extracted with CH 2 Cl 2 (3 × 50 mL). The combined extracts were dried over MgSO 4 , and the solvent was removed under reduced pressure to afford endo -5-carboxy- exo -6-phenylbicyclo[2.2.1]hept-2-ene ( 24a ) as a colorless solid (7.2 g, 56% from the iodolactone): mp 113−113.5 °C (lit . mp 113−114 °C); 1 H NMR (CDCl 3 ) δ 7.18−7.35 (m, 5H), 6.44 (dd, 5.6 Hz, 3.2 Hz, 1H, H−C3), 6.19 (dd, 5.6 Hz, 2.9 Hz, 1H, H−C2), 3.49 (s, 1H, H−C4), 3.03−3.32 (m, 3H, H−C4,5,6), 1.80 (d, 8.8 Hz, 1H, H a -C7), 1.60 (dd, 8.8 Hz, 1.7 Hz, 1H, H b -C7); IR 2700−3300, 3072, 3032, 2986, 2881, 1703, 1680 cm -1 .…”

Section: Methodsmentioning

confidence: 99%

“…The combined extracts were dried over MgSO4, and the solvent was removed under reduced pressure to afford endo-5-carboxy-exo-6-phenylbicyclo[2.2.1]hept-2-ene (24a) as a colorless solid (7.2 g, 56% from the iodolactone): mp 113-113.5 °C (lit. 40 The exo isomer 25a was isolated from the filtrate from the iodolactonization reaction described above. The basic filtrate was acidified with concentrated HCl.…”

Section: Cis-and Trans-2-(nn-dimethylaminomethyl)-3-phenylbicyclo[222...mentioning

confidence: 99%

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Synthesis and Pharmacology of Site-Specific Cocaine Abuse Treatment Agents: 2-(Aminomethyl)-3-phenylbicyclo[2.2.2]- and -[2.2.1]alkane Dopamine Uptake Inhibitors

et al. 1999

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As part of a program to develop site-specific medications for cocaine abuse, a series of 2-(aminomethyl)-3-phenylbicyclo[2.2.2]- and -[2.2.1]alkane derivatives was synthesized and tested for inhibitory potency in [3H]WIN 35,428 binding and [3H]dopamine uptake assays using rat striatal tissue. Selected compounds were tested for their ability to substitute for cocaine in rat drug discrimination tests. Synthesis was accomplished by a series of Diels-Alder reactions, using cis- and trans-cinnamic acid derivatives (nitrile, acid, acid chloride) with cyclohexadiene and cyclopentadiene. Standard manipulations produced the aminomethyl side chain. Many of the compounds bound with high affinity (median IC50 = 223 nM) to the cocaine binding site as marked by [3H]WIN 35,428. Potency in the binding assay was strongly enhanced by chlorine atoms in the 3- and/or 4-position on the aromatic ring and was little affected by corresponding methoxy groups. In the [2.2.2] series there was little difference in potency between cis and trans compounds or between N, N-dimethylamines and primary amines. In the [2.2.1] series the trans exo compounds tended to be least potent against binding, whereas the cis exo compounds were the most potent (4-Cl cis exo: IC50 = 7.7 nM, 27-fold more potent than 4-Cl trans-exo). Although the potencies of the bicyclic derivatives in the binding and uptake assays were highly correlated, some of the compounds were 5-7-fold less potent at inhibiting [3H]dopamine uptake than [3H]WIN 35,428 binding (for comparison, cocaine has a lower discrimination ratio (DR) of 2.5). The DR values were higher for almost all primary amines and for the trans-[2.2.2] series as compared to the cis-[2.2.2]. Most of the compounds had Hill coefficients approaching unity, except for the [2. 2.2] 3,4-dichloro derivatives, which all had nH values of about 2.0. Two of the compounds were shown to fully substitute for cocaine in drug discrimination tests in rats, and one had a very long duration of action.

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Section: Methodsmentioning

confidence: 99%

Section: Cis-and Trans-2-(nn-dimethylaminomethyl)-3-phenylbicyclo[222...mentioning

confidence: 99%

Synthesis and Pharmacology of Site-Specific Cocaine Abuse Treatment Agents: 2-(Aminomethyl)-3-phenylbicyclo[2.2.2]- and -[2.2.1]alkane Dopamine Uptake Inhibitors

et al. 1999

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“…A phenyl group in β-position reduces the reactivity of dienophile and, to the best of our knowledge, there was no precedent for their asymmetric Diels−Alder reaction. To access the activity of OXB catalysts 3 , we examined the reaction of benzalacetone ( 5b ) with cyclopentadiene (eq 2, Table ).…”

Section: Resultsmentioning

confidence: 93%

Oxazaborolidinone-Catalyzed Enantioselective Diels−Alder Reaction of Acyclic α,β-Unsaturated Ketones

et al. 2007

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allo-Threonine-derived O-acyl-B-phenyl-oxazaborolidinones are demonstrated to be powerful and highly enantioselective Lewis acid catalysts for the Diels-Alder reaction of simple acyclic enone dienophiles, expanding the scope of ketone dienophiles and dienes. With 10 to 20 mol % of catalyst, the Diels-Alder adducts are obtained in 76-98% ee with high endo-selectivity. The catalyst exhibits high activity for the reaction with the less reactive beta-substituted dienophiles and the less reactive 1,3-cycohexadiene and 1,3-butadiene derivatives. The application of the catalysts to the Diels-Alder reaction of furan is also described.

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“…For example, thermal reaction of 7 with β-nitrostyrene, trans -cinnimaldehyde, , or cis -ethyl cinnamate reportedly gives only low to moderate yields of the corresponding cycloadducts (20−25%, 22−54%, and 38%, respectively). Reaction of benzylidene acetone 8 with cyclopentadiene occurs in marginally better yield (35−64%), and so the reaction of 7 with 8 was chosen as an initial model for our system.…”

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confidence: 99%

Highly Selective Diels−Alder Reactions of Dienophiles with 1,3-Cyclohexadiene Mediated by Yb(OTf)₃·2H₂O and Ultrahigh Pressures

Kinsman

Kerr

2000

Org. Lett.

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[reaction: see text] Ultrahigh pressures and catalytic Yb(OTf)(3).2H(2)O were found to mediate Diels-Alder reactions of various electron-deficient dienophiles with 1,3-cyclohexadiene to produce endo-bicyclo[2.2. 2]oct-2-enes in moderate to excellent yield and selectivity. The proposed total synthesis of hapalindole Q based on bicyclo[2.2. 2]oct-2-ene construction by Diels-Alder reaction and subsequent olefin cleavage is outlined. Preliminary results demonstrating the viability of this strategy are presented.

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Bicyclic Ketones. I. Reaction of Cyclopentadiene with cis- and trans-Benzalacetone and Acetylphenylacetylene¹

Cited by 5 publications

References 0 publications

Synthesis and Pharmacology of Site-Specific Cocaine Abuse Treatment Agents: 2-(Aminomethyl)-3-phenylbicyclo[2.2.2]- and -[2.2.1]alkane Dopamine Uptake Inhibitors

Synthesis and Pharmacology of Site-Specific Cocaine Abuse Treatment Agents: 2-(Aminomethyl)-3-phenylbicyclo[2.2.2]- and -[2.2.1]alkane Dopamine Uptake Inhibitors

Oxazaborolidinone-Catalyzed Enantioselective Diels−Alder Reaction of Acyclic α,β-Unsaturated Ketones

Highly Selective Diels−Alder Reactions of Dienophiles with 1,3-Cyclohexadiene Mediated by Yb(OTf)₃·2H₂O and Ultrahigh Pressures

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Bicyclic Ketones. I. Reaction of Cyclopentadiene with cis- and trans-Benzalacetone and Acetylphenylacetylene1

Cited by 5 publications

References 0 publications

Synthesis and Pharmacology of Site-Specific Cocaine Abuse Treatment Agents: 2-(Aminomethyl)-3-phenylbicyclo[2.2.2]- and -[2.2.1]alkane Dopamine Uptake Inhibitors

Synthesis and Pharmacology of Site-Specific Cocaine Abuse Treatment Agents: 2-(Aminomethyl)-3-phenylbicyclo[2.2.2]- and -[2.2.1]alkane Dopamine Uptake Inhibitors

Oxazaborolidinone-Catalyzed Enantioselective Diels−Alder Reaction of Acyclic α,β-Unsaturated Ketones

Highly Selective Diels−Alder Reactions of Dienophiles with 1,3-Cyclohexadiene Mediated by Yb(OTf)3·2H2O and Ultrahigh Pressures

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Bicyclic Ketones. I. Reaction of Cyclopentadiene with cis- and trans-Benzalacetone and Acetylphenylacetylene¹

Highly Selective Diels−Alder Reactions of Dienophiles with 1,3-Cyclohexadiene Mediated by Yb(OTf)₃·2H₂O and Ultrahigh Pressures