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Please use this identifier to cite or link to this item: http://hdl.handle.net/10586 /456

Title: Asymmetric y-Alkoxyallylboration with the BBDs
Authors: Muñoz Hernández, Lorell
Soderquist, John A.(Consejero)
Keywords: Asymetric synthesis
BBD reagents
Soderquists reagents
Homoallylic alcohols
Homoallylic amines
Boron Chemistry
Organic Synthesis
Issue Date: 18-Jun-2014
Abstract: Reagent (Z)-(y-methoxyallyl)-10-TMS-9-BBD (Z89) was prepared to evaluate its behavior in the methoxyallylboration of aldehydes. It was prepared by metalation of allyl methyl ether with sec-butyllithium in THF at -78 oC.1 This was treated with Bmethoxy- 10-trimethylsilyl-9-BBD (86) at -78 oC to produce the organoborate complex 92 which was treated with TMSCl to generate trialkylborane 89 in 85% yield. Representative aldehydes were added to trialkylborane Z89 in THF at -78 oC to give borinate 91 which was treated with the appropriate pseudoephedrine to provide complex 87 and the desired threo-β-methoxyhomoallyl alcohols 90 in 65-96% yield with excellent diastereoselectivity (96-99%) and optical purity (98-99% ee). Racemic reagent (±)-Z89 was prepared to evaluate its thermal stability with respect to cis/trans isomerization. The pure cis geometry of trialkylborane Z89 was retained upon warming to 25 oC. After either 4 days at 36 oC or 14 h at 80 oC, a ~70:30 cis/trans mixture was formed. The selectivity of trialkylborane Z89 in its addition to N-H aldimines was examined. Aldimines were prepared by the partial reduction of the corresponding nitrile with diisobutylaluminum hydride (DIBAL-H) to produce N-diisobutylalanyl imines.2 Then, N-H aldimines were generated in situ from the methanolysis of the corresponding N-DIBAL derivatives. Addition of N-DIBAL aldimines to Z89 in THF solution at -78 oC followed by MeOH (1 equiv) resulted in the clean formation of 107 (11B NMR ~51 ppm). An acidic workup provided the corresponding threo-β- methoxyhomoallylic amines 93 in 72-96% yield, 98% de and 56-86% ee. A taxol side chain derivative (94) was synthesized from 93a through benzoylation followed by Sharpless oxidation3 in 70% overall yield. This methodology was expanded to reaction with ketones by synthesis of reagent (Z)-(y-methoxyallyl)-10-Ph-9-BBD (Z99). Trialkylborane Z99 was prepared by metalation of allyl methyl ether with sec-butyllithium in THF at -78 oC,1 then treated with B-methoxy-10-phenyl-9-BBD (96) at -78 oC to produce the organoborate complex 110 which is treated with TMSCl to generate trialkylborane Z99 in 87% yield. Further analysis of the NMR spectra after 1, 2.5 and 24 h at 25 oC showed the progress of isomerization from 16:84 (trans/cis) in 1 h to (46:54) in 24 h. Representative ketones were added to Z99 in THF at -78 oC to give 111 which was treated under oxidation conditions to provide the corresponding threo-β- methoxyhomoallylic tertiary alcohols 100 in 45-88% yield, 12-98% de (of the crude product) and 68-98% ee. 3,3-dimethylbutan-2-one (71d) gave almost exclusively the anti diastereomer (100d), suggesting reaction of ketone with the trans-trialkyl borane. This methodology was used in the synthesis of a precursor of fostriecin, a phosphate ester that displays antitumor activity against various tumor cell lines and in vivo anticancer activity against leukemia.4 The synthesis of 101 was accomplished from ketone Z112 through alkoxyallylboration with trialkylborane ZS113 in 81% yield, 94% de and 82% ee. The enamine/ketimine mixture 119a and 120a from the methylation/silylation of benzonitrile was added to ZS99 and ZS113 in THF at -78 oC and was treated under oxidation conditions to provide the corresponding threo-β-methoxyhomoallylic tertiary amines 104 in 57-64% yield, 90-98% de and 92-94% ee. In contrast to the stereochemistry observed with the unsubstituted allyl BBD reagent 74, the Z-γ- substituted allyl reagents provide the product amines with the oppositite absolute configuration. While the syn product is consistent with the rapid reaction of these Zreagents, interactions between the ketimine’s N-TMS group and the γ-alkoxy group on the allylic portion of the borane is believed to result in a preferred upside-down orientation (i.e., 123) for the allylation which can occur through a Zimmerman-Traxler chair-like transition state to give the observed product stereochemistry.
URI: http://hdl.handle.net/10586 /456
Appears in Collections:Departamento de Química

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