Asymmetric syntheses of anthraquinonyl C-glycosides

by Bercich, Mark David

Abstract (Summary)
Syntheses of C2-anthraquinone aldehydes from the commercially available anthrarufin 11 have been investigated. A synthesis of the ketoaldehyde 5 in nine steps and 73% overall yield was achieved. Syntheses of 5 exploiting selective oxidations of either a C-bound allyl group via Wacker oxidation to introduce the methyl ketone functionality, or of a C-bound prop-l-enyl moiety via dihydroxylation and oxidative cleavage to generate the C2 formyl group were also developed. The aldehyde 81 was synthesised in seven steps and 81% overall yield from ll, and syntheses of the phenolic aldehydes 82, 95, and 96, the Cl benzyloxyaldehyde 104, and the anthracene aldehyde 107 have been developed. Hetero Diels-Alder reactions of several anthraquinone aldehydes with the dienes 6,120, and 121 using catalysis by the complex (+)-VO(hfc)2 115 were studied. Reactions of the aldehydes 5 and 81 proceeded readily using catalytic amounts of 115 and dichloromethane, chloroform, or toluene as solvent to give the adducts 128 or 131 indicating an endo selective pericyclic reaction pathway. The enantioselectivites of these reactions were typically 20-50%, with a best ee of 56% for a reaction between 81 and 6 catalysed by 0.2 equivalents of 115 at -78°C. Reactions of the 1-silyloxydienes 120 and 121 with aldehyde 8l catalysed by 115 to give the enone 130 also proceeded readily with a best ee of 64% being obtained for a reaction between 81 and l2l in toluene at -78°C. Reactions of the phenolic aldehydes 95 and 96 and the diene 6, catalysed by 115, afforded good yields of cycloadducts, but with enantioselectivities identical to equivalent reactions of the aldehyde 81. However reactions of the Cl benzyloxyaldehyde 104 with the dienes 6 and 120, and 121 afforded cycloadducts with enantioselectivities lower than those from the equivalent reactions of the aldehyde 81. Elaboration of the cycloadduct 131 to the anthracene C-glycoside 149 established that the hetero Diels-Alder reaction had favoured the formation of the 2'R, 6'R enantiomer of 131. This enantiofacial selectivity was correlated with the sense of anisochrony observed in 1H NMR spectra of the ketone 129, derived from 131, in the presence of the chiral solvating agent (S)(+)-trifluoroanthrylethanol. The enone 130 was elaborated to the anthraquinone-olivose C-glycoside 154 demonstrating the utility of hetero Diels-Alder reactions involving silyloxydienes with Cl silyloxy and Cl methyl substituents for such syntheses. Attempts to use chiral acyloxyborane comploxes such as 168 and 169 as catalysts for hetero Diels-Alder reactions of the aldehydes 5, 81 and 107 with the dienes 6 and 120 were unsuccessful. However two equivalents of the chiral acyloxyborane complex 168a in dichloromethane at 30°C, mediated. a formal hetero Diels-Alder reaction between 81 and 120 affording the enone 13O in 45% yield, with a 79% ee in favour of the 6'R enantiomer. Reactions catalysed by the chiral acyloxyborane complex 169b between beenzaldehyde or o-anisaldehyde and the dienes 6,119, and 120 gave products resulting from a Mukaiyama aldol addition rather than a hetero Diels-Alder reaction. Hetero Diels-Alder reactions 81 and 120 employing the chiral titanium complexes Ti[(R)-BINOL]C12, Ti[(R)-BINOL]2, and Ti[R,R)-TADDOL]C12 were investigated. No reaction was observed when 0.5, 1.2 and 2 equivalents of Ti[(R)-BINOL]2 were used. However the complexes Ti[(R)-BINOL]C12 and Ti[(R,R)-TADDOL]C12 promoted the reaction between 81 and 120 at -30°C and -78°C, but induced low enantioselectivities (17-30%)
Bibliographical Information:

Advisor:Assoc. Professor Stewart Rutledge

School:The University of Auckland / Te Whare Wananga o Tamaki Makaurau

School Location:New Zealand

Source Type:Master's Thesis



Date of Publication:01/01/1997

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