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Volumn 130, Issue 39, 2008, Pages 12904-12906

Enantioselective total synthesis of clavirolide C. applications of Cu-catalyzed asymmetric conjugate additions and Ru-catalyzed ring-closing metathesis

Author keywords

[No Author keywords available]

Indexed keywords

ALKYLALUMINUM; ASYMMETRIC CONJUGATE ADDITION; C-SYNTHESIS; CHEMICAL EQUATIONS; CHIRAL AMINO ACIDS; CYCLOALKENONES; DITERPENES; ENANTIOSELECTIVE; ENANTIOSELECTIVE TOTAL SYNTHESIS; LINEAR SEQUENCE; NATURAL PRODUCTS; NEW PROTOCOL; RING CLOSING METATHESIS; RING STRUCTURES; TARGET MOLECULE; TOTAL SYNTHESIS;

EID: 58149165238     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja8058414     Document Type: Article
Times cited : (103)

References (47)
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    • Three cases of ACA of trialkylaluminum reagents to β-substituted cyclopentenones, catalyzed by chiral Cu-phosphoramidites, have been reported. High selectivity and efficiency are observed in only one instance involving a relatively reactive nucleophile (Et3Al: 96.5:3.5 er, 93% ee). See: Vuagnoux-d'Augustin, M.; Alexakis, A. Chem. - Eur. J. 2007, 13, 9647-9662, and references cited therein.
    • Three cases of ACA of trialkylaluminum reagents to β-substituted cyclopentenones, catalyzed by chiral Cu-phosphoramidites, have been reported. High selectivity and efficiency are observed in only one instance involving a relatively reactive nucleophile (Et3Al: 96.5:3.5 er, 93% ee). See: Vuagnoux-d'Augustin, M.; Alexakis, A. Chem. - Eur. J. 2007, 13, 9647-9662, and references cited therein.
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    • (a) Brown, M. K.; May, T. L.; Baxter, C. A.; Hoveyda, A. H. Angew Chem., Int. Ed. 2008, 46, 1097-1100. One application of catalytic ACA promoted by a chiral NHC·Cu complex (derived from 1) to natural product synthesis has appeared. The transformation, however, involves a six-membered ring enone bearing an activating β-substituent.
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    • For related diastereoselective aldol additions involving boron enolates, see: Yamamoto, Y.; Yatagai, H.; Maruyama, K. Tetrahedron Lett. 1982, 23, 2387-2390.
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    • The diastereomeric ratio can be increased from 1.5:1 to 4:1 (C1-C11) through partial separation of diastereomers by silica gel column chromatography. Silyl ether diastereomers (at C6) undergo Ru-catalyzed RCM with equal facility.
    • The diastereomeric ratio can be increased from 1.5:1 to 4:1 (C1-C11) through partial separation of diastereomers by silica gel column chromatography. Silyl ether diastereomers (at C6) undergo Ru-catalyzed RCM with equal facility.
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    • Under rigorously anhydrous conditions, 5 mol % 13 can be used to obtain similar results. With 20 mol % 13, yields exceed 80% without resorting to the use of strictly anhydrous conditions.
    • Under rigorously anhydrous conditions, 5 mol % 13 can be used to obtain similar results. With 20 mol % 13, yields exceed 80% without resorting to the use of strictly anhydrous conditions.
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    • Use of sterically and electronically modified versions of complex 13 leads to the formation of 14 with similar efficiency. For a discussion of the utility of such complexes and the attributes of phosphine-free Ru-based carbenes in catalytic olefin metathesis, see: Hoveyda, A. H.; Gillingham, D. G.; Van Veldhuizen, J. J.; Kataoka, O.; Garber, S. B.; Kingsbury, J. S.; Harrity, J. P. A. Org. Biomol. Chem. 2004, 2, 8-23.
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    • A similar sequence has been carried en route to the clavirolides; see ref 2a,b
    • A similar sequence has been carried en route to the clavirolides; see ref 2a,b.
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    • 2CuLi·LiI followed by aqueous workup, the 3:1 mixture at C18 is transformed to a single stereoisomer (R).
    • 2CuLi·LiI followed by aqueous workup, the 3:1 mixture at C18 is transformed to a single stereoisomer (R).
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    • See Supporting Information for additional details, including relevant X-ray data
    • See Supporting Information for additional details, including relevant X-ray data.
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    • See Supporting Information for complete spectral and physical data
    • See Supporting Information for complete spectral and physical data.
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    • Due to the substantial difference in size of the substituents R to the enolsilane (e.g., H vs alkyl), this stereochemical issue is more easily addressed in the catalytic ACA/aldol sequence involving non-β-substituted cycloalkenones. For example, see: Arnold, L. A.; Naasz, R.; Minnaard, A. J.; Feringa, B. L. J. Am. Chem. Soc. 2001, 123, 5841-5842.
    • Due to the substantial difference in size of the substituents R to the enolsilane (e.g., H vs alkyl), this stereochemical issue is more easily addressed in the catalytic ACA/aldol sequence involving non-β-substituted cycloalkenones. For example, see: Arnold, L. A.; Naasz, R.; Minnaard, A. J.; Feringa, B. L. J. Am. Chem. Soc. 2001, 123, 5841-5842.
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    • Enantioselective aldol additions of five-membered ring enolsilanes to aryl-derived aldehydes have been reported. Reactions with alkyl-substituted aldehydes, however, are either inefficient or not included in such disclosures. See: (a) Denmark, S. E, Stavenger, R. A, Wong, K-.T. Tetrahedron 1998, 54, 10389-10402
    • Enantioselective aldol additions of five-membered ring enolsilanes to aryl-derived aldehydes have been reported. Reactions with alkyl-substituted aldehydes, however, are either inefficient or not included in such disclosures. See: (a) Denmark, S. E.; Stavenger, R. A.; Wong, K-.T. Tetrahedron 1998, 54, 10389-10402.


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