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Volumn 63, Issue 1, 2007, Pages 77-85

α,β-Unsaturated diesters: radical acceptors in dialkylzinc-mediated tandem radical addition/aldol condensation. A straightforward synthesis of rac-nephrosteranic acid

Author keywords

Conjugate addition; Diethylzinc; Dimethylzinc; Radical polar crossover reaction; Lactones

Indexed keywords

ACID; ALKYL GROUP; DIETHYLZINC; ESTER DERIVATIVE; FUMARIC ACID; GAMMA LACTONE DERIVATIVE; MALEIC ACID; METHYL GROUP; NEPHROSTERANIC ACID; ZINC DERIVATIVE;

EID: 33751525766     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tet.2006.10.049     Document Type: Article
Times cited : (61)

References (74)
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    • Although the mechanism was not interpreted as a radical pathway, see also:
    • Although the mechanism was not interpreted as a radical pathway, see also:. Charette A.B., Beauchemin A., and Marcoux J.-F. J. Am. Chem. Soc. 120 (1998) 5114-5115
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    • note
    • Substituent effects influence spin delocalization at oxygen. Theoretical calculations at the UB3LYP/6-311++G(3df,3pd)//UB3LYP6-31+G(d,p) level of theory confirmed that going from primary to secondary α-alkoxycarbonylalkyl radical results in decrease of spin density at the oxygen atom (0.218, 0.168, respectively). The additional substituent in tertiary α-alkoxycarbonylalkyl radicals does not confirm this trend and a slight increase in spin density at oxygen is registered (0.176). The difference in spin density between the secondary and the tertiary radical is not significant enough to correlate their reactivity to this sole parameter. We suspect that prior complexation of the radical to zinc might be a requirement to meet for the homolytic substitution at zinc to proceed. Therefore, steric impediment to the donor-acceptor interaction might be as important as spin density at oxygen for zinc enolates to be formed.
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    • The involvement of chelated enolates has been suggested to explain the diastereoselectivity in some aldol condensation of zinc enolates. See:
    • The involvement of chelated enolates has been suggested to explain the diastereoselectivity in some aldol condensation of zinc enolates. See:. Lai S., Zercher C.K., Jasinski J., Reid S.N., and Staples R. Org. Lett. 3 (2001) 4169-4171
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    • note
    • Indeed, we have shown that even secondary α-alkoxycarbonylalkyl radicals derived from α,β-unsaturated monoesters reacted by homolytic substitution at zinc since it was possible to perform tandem radical addition/aldol condensation with ethyl acrylate in the presence of diethylzinc, tert-butylI and benzaldehyde. The multi-component process led to a 68:32 mixture of diastereomeric aldols isolated in 87% yield.
  • 48
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    • Maleates are less reactive than fumarates by a factor of 7.5 with respect to the addition of methyl radical. This is likely to result from steric interactions preventing the two carbonyl groups to be fully conjugated with the double bond, see:
    • Maleates are less reactive than fumarates by a factor of 7.5 with respect to the addition of methyl radical. This is likely to result from steric interactions preventing the two carbonyl groups to be fully conjugated with the double bond, see:. Bader A.R., Buckley R.P., Leavitt F., and Szwarc M. J. Am. Chem. Soc. 79 (1957) 5621-5625
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    • note
    • According to Tomioka's reports in Ref. 3, the addition of methyl radical to the C{double bond, long}N bond of imines does not compete with hydrogen transfer from THF or cycloalkanes. It does not compete either with iodine transfer from alkyl iodides. A similar observation has been made by Naito and co-workers using glyoxylic oxime ethers (Ref. 2g).
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    • For syntheses of phaseolinic acid, see:
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    • For syntheses of nephrosteranic and roccelaric acids, see:


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.