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Volumn , Issue 1, 2006, Pages 246-256

Preparation of conformationally constrained α 2- antagonists: The bicyclo[3.2.0]heptane approach

Author keywords

Adrenergic antagonists; Cycloaddition; Cyclobutanes; Fused ring systems; Strained molecules

Indexed keywords


EID: 64549130327     PISSN: 1434193X     EISSN: None     Source Type: Journal    
DOI: 10.1002/ejoc.200500541     Document Type: Article
Times cited : (11)

References (84)
  • 3
    • 29744446597 scopus 로고    scopus 로고
    • note
    • c) Only a single enantiomer is shown for clarity, even though racemates were synthesized throughout this work.
  • 23
    • 0011211276 scopus 로고
    • a) We found few examples of cycloadditions of ketenes with tri- and tetrasubstituted olefins but not with indenes: D. A. Bak, W. T. Brady, J. Org. Chem. 1979, 44, 107-110.
    • (1979) J. Org. Chem. , vol.44 , pp. 107-110
    • Bak, D.A.1    Brady, W.T.2
  • 24
    • 29744464835 scopus 로고    scopus 로고
    • note
    • [5a] it was reported that 1-methylcyclohexene gave a 4:1 mixture of regioisomeric cyclobutanones in the [2+2] cycloaddition with ketene.
  • 25
    • 29744453240 scopus 로고
    • Intramolecular [2+2] Cycloadditions of Ketenes and Olefins
    • (Eds.: A. de Meijere, S. Blechert), Kluwer Academic Publishers, Norwell, MA
    • B. Ernst, A. de Mesmaeker, H. Greuter, S. J. Veenstra, "Intramolecular [2+2] Cycloadditions of Ketenes and Olefins" in Strain and Its Implications in Organic Chemistry (Eds.: A. de Meijere, S. Blechert), Kluwer Academic Publishers, Norwell, MA, 1989, pp. 207-234;
    • (1989) Strain and Its Implications in Organic Chemistry , pp. 207-234
    • Ernst, B.1    De Mesmaeker, A.2    Greuter, H.3    Veenstra, S.J.4
  • 26
    • 0004297838 scopus 로고    scopus 로고
    • Hypercube, Gainesville, USA
    • CNDO calculations (HyperChem, version 5.1, Hypercube, Gainesville, USA) indicated that the largest coefficient for the HOMO of styrenes 3a and 3b is on the terminal carbon atom of the vinyl group. The [3.2.0] system should therefore be favored over the [3.1.1] one.
    • HyperChem, Version 5.1
  • 28
    • 0001740156 scopus 로고
    • Ketene Cycloadditions
    • (Ed.: L. A. Paquette), Wiley, New York, chapter 2
    • J. A. Hyatt, P. W. Raynolds, "Ketene Cycloadditions" in Organic Reactions, vol. 45 (Ed.: L. A. Paquette), Wiley, New York, 1994, chapter 2, pp. 162-646;
    • (1994) Organic Reactions , vol.45 , pp. 162-646
    • Hyatt, J.A.1    Raynolds, P.W.2
  • 32
    • 0642284306 scopus 로고
    • The authors described a [2+2] cycloaddition between an arylketene and a homobenzylic alkene which gave isomeric cyclobutanones (see also: B. B. Snider, E. Ron, B. W. Burbaum, J. Org. Chem. 1987, 52, 5413-5419).
    • (1987) J. Org. Chem. , vol.52 , pp. 5413-5419
    • Snider, B.B.1    Ron, E.2    Burbaum, B.W.3
  • 33
    • 29744470519 scopus 로고    scopus 로고
    • New Polycyclic Indanylimidazoles with Alpha2 Adrenergic Activity, WO 85698, 2001
    • b) While this work was in progress, Orion Corporation published a patent application in which compounds related to 1 were claimed. In this application, however, it was not clear how the 1,2,2a,7-tetrahydrocyclobut[a]indene skeleton had been prepared. Moreover, neither experimental protocols nor characterization data were provided to support structure identification: Orion Corporation, New Polycyclic Indanylimidazoles with Alpha2 Adrenergic Activity, WO 85698, 2001; Chem. Abstr. 2001, 135, 357928.
    • (2001) Chem. Abstr. , vol.135 , pp. 357928
  • 35
    • 0005933054 scopus 로고
    • Attempts at generating ketene 3 by dehydrohalogenation (W. T. Brady, Y. F. Giang, J. Org. Chem. 1985, 50, 5177)
    • (1985) J. Org. Chem. , vol.50 , pp. 5177
    • Brady, W.T.1    Giang, Y.F.2
  • 37
    • 29744461827 scopus 로고
    • Preparation of Ketenes
    • Wiley & Sons, New York, chapter 3
    • For a review on methods used to generate ketenes, see: T. T. Tidwell, "Preparation of Ketenes" in Ketenes, Wiley & Sons, New York, 1995, chapter 3.
    • (1995) Ketenes
    • Tidwell, T.T.1
  • 40
    • 29744452526 scopus 로고    scopus 로고
    • note
    • 4 gave 10 as the sole product (89% yield). Analytical data for the diester 8 and diol 10 are given in the Supporting Information. The stereochemical relationship between the chains was established by NOE experiments.
  • 41
    • 29744444094 scopus 로고    scopus 로고
    • note
    • Treatment of 2b with EtONa/EtOH also returned the indane as a mixture of isomers (8/9 = 6:4).
  • 42
    • 84989473405 scopus 로고
    • An example of a bicyclo[3.2.0]heptane-type derivative that ring-opens without activation by a 1,3-dicarbonyl group: C.-S. Hwang, W. Reusch, Synthesis 1989, 428-434.
    • (1989) Synthesis , pp. 428-434
    • Hwang, C.-S.1    Reusch, W.2
  • 43
    • 29744441132 scopus 로고    scopus 로고
    • note
    • The most obvious way to avoid having a reactive 1,3-dicarbonyl group in the cycloadduct would be to perform the cycloaddition using precursors such as 39 (see below). Unfortunately, the cycloaddition failed (see Supporting Information for characterization of 39) which highlighted the importance of ketene activation by the ester function. (Chemical Equation Presented)
  • 44
    • 29744434865 scopus 로고    scopus 로고
    • note
    • Both isomers were separated by chromatography on silica gel (cf. Exp. Sect.).
  • 45
    • 29744463807 scopus 로고    scopus 로고
    • note
    • Reduction of 2b with DIBAL produced 12-endo/exo = 80:20 (60% combined yield). The stereogenic centre at C-1 was destroyed during the synthesis of 1.
  • 46
    • 29744446596 scopus 로고    scopus 로고
    • note
    • The various methods used are summarized in the Supporting Information.
  • 47
    • 29744450062 scopus 로고    scopus 로고
    • note
    • Although a triphenylmethyl protecting group was introduced with a better regioselectivity than a pivaloyl or a TBDMS group (see Supporting Information), its high molecular weight and sensitivity towards acids or hydrogenolysis were deemed prohibitive.
  • 49
    • 29744431845 scopus 로고    scopus 로고
    • note
    • a) The use of metal hydrides as reducing agents gave the endoalcohol preferentially whatever the protecting group "P" on the primary alcohol. (Chemical Equation Presented)
  • 54
    • 0030458106 scopus 로고    scopus 로고
    • For concomitant reduction of Inflates and double bonds, see: D. Comins, Y. Zhang, J. Am. Chem. Soc. 1996, 118, 12248-12249.
    • (1996) J. Am. Chem. Soc. , vol.118 , pp. 12248-12249
    • Comins, D.1    Zhang, Y.2
  • 55
    • 29744435032 scopus 로고    scopus 로고
    • note
    • Chromatographic separation proved impractical for the alcohol 33, the ester 38 and the final imidazoline 1.
  • 62
    • 0001375382 scopus 로고
    • The reduction in presence of Wilkinson's catalyst required prolonged heating (24 h of refluxing in ethanol). Under these conditions, no isomerization of the double bond to an intracyclic position was detected: R. C. Ronald, M. B. Gewali, B. P. Ronald, J. Org. Chem. 1980, 45, 2224-2229.
    • (1980) J. Org. Chem. , vol.45 , pp. 2224-2229
    • Ronald, R.C.1    Gewali, M.B.2    Ronald, B.P.3
  • 63
    • 29744441714 scopus 로고    scopus 로고
    • note
    • Selectivity of the catalytic hydrogenations was checked at almost every stage en route to 1 (see Supporting Information), but the level of exo selectivity never exceeded that obtained for 28 or 29.
  • 72
    • 29744463072 scopus 로고    scopus 로고
    • note
    • We could not prepare the enol triflate from the keto ester 2b. We believe that a competing retro-cyclization might be interfering. (Chemical Equation Presented)
  • 73
    • 29744452310 scopus 로고    scopus 로고
    • note
    • α and the methyl group at C-2a). (Chemical Equation Presented)
  • 76
    • 0030607168 scopus 로고    scopus 로고
    • Compound 28 did not react with Schwartz's reagent in THF or toluene, even upon heating: P. Wipf, H. Jahn, Tetrahedron 1996, 52, 12853-12910;
    • (1996) Tetrahedron , vol.52 , pp. 12853-12910
    • Wipf, P.1    Jahn, H.2
  • 79
    • 0344361777 scopus 로고
    • 2H, various temperatures), only traces of the reduced material were formed (<5% by HPLC): H. C. Brown, K.J. Murray, Tetrahedron 1986, 42, 5497-5504.
    • (1986) Tetrahedron , vol.42 , pp. 5497-5504
    • Brown, H.C.1    Murray, K.J.2
  • 83
    • 29744468089 scopus 로고    scopus 로고
    • note
    • Work aimed at reducing 28 in an exo-selective manner is still in progress.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.