Article

Flexible synthesis of enantiomerically pure 2,8-dialkyl-1,7-dioxaspiro[5.5]undecanes and 2,7-dialkyl-1,6-dioxaspiro[4.5]decanes from propargylic and homopropargylic alcohols.

School of Molecular and Microbial Sciences, Department of Chemistry, The University of Queensland, Brisbane, Australia 4072.
The Journal of Organic Chemistry (Impact Factor: 4.56). 05/2005; 70(8):3054-65. DOI: 10.1021/jo0477547
Source: PubMed

ABSTRACT A new approach to enantiomerically pure 2,8-dialkyl-1,7-dioxaspiro[5.5]undecanes and 2,7-dialkyl-1,6-dioxaspiro[4.5]decanes is described and utilizes enantiomerically pure homopropargylic alcohols obtained from lithium acetylide opening of enantiomerically pure epoxides, which are, in turn, acquired by hydrolytic kinetic resolution of the corresponding racemic epoxides. Alkyne carboxylation and conversion to the Weinreb amide may be followed by triple-bond manipulation prior to reaction with a second alkynyllithium derived from a homo- or propargylic alcohol. In this way, the two ring components of the spiroacetal are individually constructed, with deprotection and cyclization affording the spiroacetal. The procedure is illustrated by acquisition of (2S,5R,7S) and (2R,5R,7S)-2-n-butyl-7-methyl-1,6-dioxaspiro[4.5]-decanes (1), (2S,6R,8S)-2-methyl-8-n-pentyl-1,7-dioxaspiro[5.5]undecane (2), and (2S,6R,8S)-2-methyl-8-n-propyl-1,7-dioxaspiro[5.5]undecane (3). The widely distributed insect component, (2S,6R,8S)-2,8-dimethyl-1,7-dioxaspiro[5.5]undecane (4), was acquired by linking two identical alkyne precursors via ethyl formate. In addition, [(2)H(4)]-regioisomers, 10,10,11,11-[(2)H(4)] and 4,4,5,5-[(2)H(4)] of 3 and 4,4,5,5-[(2)H(4)]-4, were acquired by triple-bond deuteration, using deuterium gas and Wilkinson's catalyst. This alkyne-based approach is, in principle, applicable to more complex spiroacetal systems not only by use of more elaborate alkynes but also by triple-bond functionalization during the general sequence.

0 Bookmarks
 · 
64 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: In pursuit of a more environmentally benign method of controlling the highly pestiferous Queensland fruit fly, Bactrocera tryoni, the biosynthesis of the minor components in the suite of spiroacetals released by females has been investigated. This follows on the biosynthetic definition of the pathway to the major component, (E,E)-1. The origins of the C(12) and C(13) spiroacetals (E,E)-2 and (E,E)-3, respectively, have been investigated by the administration of over 30 deuterated potential precursors. Analysis of the relative incorporation levels and identification of some of the exceptionally minor spiroacetals that were biosynthesised established that B. tryoni processes fatty acids to 2,6-dioxygenated precursors by a modified β-oxidation pathway, with a suite of putative cytochromes P450 employed in the crucial oxidative steps, prior to cyclisation of the proposed ketodiol.
    ChemBioChem 01/2011; 12(1):155-72. · 3.74 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chiral biphenols catalyze the enantioselective asymmetric propargylation of ketones using allenylboronates. The reaction uses 10 mol % of 3,3'-Br(2)-BINOL as the catalyst and allenyldioxoborolane as the nucleophile, in the absence of solvent, and under microwave irradiation to afford the homopropargylic alcohol. The reaction products are obtained in good yields (60-98%) and high enantiomeric ratios (3:1-99:1). Diastereoselective propargylations using chiral racemic allenylboronates result in good diastereoselectivities (dr >86:14) and enantioselectivities (er >92:8) under the catalytic conditions.
    Organic Letters 08/2011; 13(15):4020-3. · 6.14 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: An efficient asymmetric synthesis of cyclo-archaeol and β-glucosyl cyclo-archaeol is presented employing catalytic asymmetric conjugate addition and catalytic epoxide ring opening as the key steps. Their occurrence in deep sea hydrothermal vents has been confirmed by chromatographic comparison with natural samples.
    Organic & Biomolecular Chemistry 02/2013; · 3.57 Impact Factor