Efficient Synthesis of 1,1‘-Binaphthyl and 2,2‘-Bi-<i>o</i>-tolyl-2,2‘-bis(oxazoline)s and Preliminary Use for the Catalytic Asymmetric Allylic Oxidation of Cyclohexene

Andrus, Merritt B.; Asgari, Davoud; Sclafani, Joseph A.

doi:10.1021/jo9713619

Cited by 92 publications

(27 citation statements)

References 26 publications

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“…Andrus and co-workers have further probed the effect of additional stereogenicity in the bis(oxazoline) backbone by employing the diastereoisomeric biaryl atropisomeric oxazolines 20, (Scheme 8). [9,10] The wider bite angle between the two nitrogen atoms and the copper center was expected to improve selectivity for both ligands, by forcing the reacting allyl and benzoate groups closer together in 4. However, it was found that the (S,S,S)-oxazoline 20 a gave much better stereocontrol than the related (S,R,S) stereoisomer 20 b (76 % yield, 0 % ee).…”

Section: Catalytic Allylic Oxidation Of Alkenes Using An Asymmetricmentioning

confidence: 99%

Catalytic Allylic Oxidation of Alkenes Using an Asymmetric Kharasch–Sosnovsky Reaction

Eames

Watkinson

2001

Angew. Chem. Int. Ed.

234

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Kharasch and Sosnovsky reported the allylic oxidation of alkenes to give racemic allylic benzoates. This could be achieved efficiently using a tert‐butyl perester as the oxidant, in the presence of a copper or cobalt salt. The use of C2‐symmetric bis(oxazoline) ligands in the presence of copper(I) triflate with cyclic olefinic substrates gave the first synthetically useful asymmetric variant. The enantioselective control was good (up to 84 % ee) although yields were variable. In all cases the facial preference of the newly formed C−O bond was the same giving an S configuration at the allylic stereocenter. Lower stereocontrol was observed for large‐ring alkenes and substantially reduced enantioselectivities were found with open‐chain alkenes. This reaction has been further screened using a variety bis(oxazoline) and proline‐derived ligands, which give a direct correlation between the chirality of the ligand and the enantioselectivity obtained. Individual substrates were found to be extremely sensitive to both the ligand structure and copper salt used as well as the presence of additives such as zinc, hydrazine, and molecular sieves.

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Section: Catalytic Allylic Oxidation Of Alkenes Using An Asymmetricmentioning

confidence: 99%

Catalytic Allylic Oxidation of Alkenes Using an Asymmetric Kharasch–Sosnovsky Reaction

Eames

Watkinson

2001

Angew. Chem. Int. Ed.

234

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“…22) Condensation of 9 and 7-methoxy-2,2-dimethyl-2H-1-benzopyran-5-ylamine 21) (13) gave the corresponding carboxylic diarylamine 14 in 18% yield. Cyclization to the corresponding acridone 15 was achieved in 27% yield by the use of trifluoroacetic anhydride in dichloromethane, which had previously given good results in the course of related syntheses.…”

Section: Chemistrymentioning

confidence: 99%

Synthesis and Cytotoxic Activity of Acronycine Analogues in the Benzo[c]pyrano[3,2-h]acridin-7-one and Naphtho[1,2-b][1,7] and [1,10]-Phenanthrolin-7(14H)-one Series

Bongui

Elomri

Cahard

et al. 2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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The pyranoacridone alkaloid acronycine (1), isolated from Acronychia baueri SCHOTT (Rutaceae) [1][2][3] has shown antitumor properties in a panel of murine solid tumor models, including S-180 and AKR sarcomas, X-5563 myeloma, S-115 carcinoma, and S-91 melanoma. 4,5) However, its moderate potency and poor solubility in aqueous solvents severely hampered the subsequent clinical trials, which were rapidly discontinued, due to modest therapeutic effects and dose-limiting gastrointestinal toxicity after oral administration. 6) Consequently, the development of structural analogues with increased potency and/or better water solubility was highly desirable.Our efforts to design more potent derivatives were guided by the hypothesis of bioactivation of the 1,2-double bond of acronycine into the corresponding epoxide in vivo.7) The high reactivity of acronycine 1,2-epoxide, which readily reacts with water to give the corresponding cis and trans diols, suggested that this compound could be the active metabolite of acronycine, able to alkylate some nucleophilic target within the tumor cell. Accordingly, significant improvements in terms of potency were obtained with derivatives modified in the pyran ring, which had a similar reactivity toward nucleophilic agents as acronycine epoxide but improved chemical stability. Such compounds are exemplified by diesters of cis-1,2-dihydroxy-1,2-dihydroacronycine 8) and diesters of cis-1, 2-dihydroxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one in the related benzo[b]acronycine series.9) A representative of this latter type of compounds, diacetate 2, developed under the code S23906-1 is currently in phase I clinical trials. The mechanism of its action implies alkylation of the 2-amino group of DNA guanine residues by the carbocation resulting from the elimination of the ester-leaving group at position 1 of the drug. [10][11][12][13] In a continuation of recent studies of the structure-activity relationships in the acronycine series, [14][15][16][17] we describe here the synthesis and biological activities of 6-methoxy-3,3,14-trimethyl-3,14-dihydro-7H-benzo[c]pyrano[3,2-h]acridin-7-one (ϭbenzo[c]acronycine) (3) and 6,7-dimethoxy-3,3-dimethyl-3H-benzo[c]pyrano[3,2-h]acridine (4). These isomers 3 and 4 of benzo[b]acronycine (5) were prepared together with some corresponding derivatives in the cis-1,2-dihydroxy-1,2-dihydro series to determine the influence of the position of the additional aromatic ring fused onto the basic tetracyclic pyranoacridone core of acronycine on the cytotoxic activity. Also, the three compounds 6-8 in which the dimethylpyran ring present in 3 and 4 is replaced by a pyri- * To whom correspondence should be addressed. Condensation of 1-bromo-2-naphthalenecarboxylic acid (9) with 7-methoxy-2,2-dimethyl-2H-1-benzopyran-5-ylamine (13)

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“…The first asymmetric version of the Kharash-Sosnovsky reaction was reported in 1965 by Denney et al [8], though the enantioselectivity was not very good. Better enantioselectivity control has started to appear recently [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. Among them, some of them are of non C 2 -symmetry [18,25,26].…”

Section: Introductionmentioning

confidence: 99%

New chiral bidentate ligands containing thiazolyl and pyridyl donors for copper-catalyzed asymmetric allylic oxidation of cyclohexene

Teng

Tsang

Yeung

et al. 2006

Journal of Organometallic Chemistry

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Efficient Synthesis of 1,1‘-Binaphthyl and 2,2‘-Bi-o-tolyl-2,2‘-bis(oxazoline)s and Preliminary Use for the Catalytic Asymmetric Allylic Oxidation of Cyclohexene

Cited by 92 publications

References 26 publications

Catalytic Allylic Oxidation of Alkenes Using an Asymmetric Kharasch–Sosnovsky Reaction

Catalytic Allylic Oxidation of Alkenes Using an Asymmetric Kharasch–Sosnovsky Reaction

Synthesis and Cytotoxic Activity of Acronycine Analogues in the Benzo[c]pyrano[3,2-h]acridin-7-one and Naphtho[1,2-b][1,7] and [1,10]-Phenanthrolin-7(14H)-one Series

New chiral bidentate ligands containing thiazolyl and pyridyl donors for copper-catalyzed asymmetric allylic oxidation of cyclohexene

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