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Synthesis of 1-methyl-6,10-diphenylheptalene derivatives


Jin, X; Linden, A; Hansen, H J (2010). Synthesis of 1-methyl-6,10-diphenylheptalene derivatives. Helvetica Chimica Acta, 93(4):729-745.

Abstract

The reduction of heptalene diester 1 with diisobutylaluminium hydride (DIBAH) in THF gave a mixture of heptalene-1,2-dimethanol 2a and its double-bond-shift (DBS) isomer 2b (Scheme 3). Both products can be isolated by column chromatography on silica gel. The subsequent chlorination of 2a or 2b with PCl5 in CH2Cl2 led to a mixture of 1,2-bis(chloromethyl)heptalene 3a and its DBS isomer 3b. After a prolonged chromatographic separation, both products 3a and 3b were obtained in pure form. They crystallized smoothly from hexane/Et2O 7 : 1 at low temperature, and their structures were determined by X-ray crystal-structure analysis (Figs. 1 and 2). The nucleophilic exchange of the Cl substituents of 3a or 3b by diphenylphosphino groups was easily achieved with excess of (diphenylphospino)lithium (=lithium diphenylphosphanide) in THF at 0° (Scheme 4). However, the purification of 4a/4b was very difficult since these bis-phosphines decomposed on column chromatography on silica gel and were converted mostly by oxidation by air to bis(phosphine oxides) 5a and 5b. Both 5a and 5b were also obtained in pure form by reaction of 3a or 3b with (diphenylphosphinyl)lithium (=lithium oxidodiphenylphospanide) in THF, followed by column chromatography on silica gel with Et2O. Carboxaldehydes 7a and 7b were synthesized by a disproportionation reaction of the dimethanol mixture 2a/2b with catalytic amounts of TsOH. The subsequent decarbonylation of both carboxaldehydes with tris(triphenylphosphine)rhodium(1+) chloride yielded heptalene 8 in a quantitative yield. The reaction of a thermal-equilibrium mixture 3a/3b with the borane adduct of (diphenylphosphino)lithium in THF at 0° gave 6a and 6b in yields of 5 and 15%, respectively (Scheme 4). However, heating 6a or 6b in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) in toluene, generated both bis-phosphine 4a and its DBS isomer 4b which could not be separated. The attempt at a conversion of 3a or 3b into bis-phosphines 4a or 4b by treatment with t-BuLi and Ph2PCl also failed completely. Thus, we returned to investigate the antipodes of the dimethanols 2a, 2b, and of 8 that can be separated on an HPLC Chiralcel-OD column. The CD spectra of optically pure (M)- and (P)-configurated heptalenes 2a, 2b, and 8 were measured (Figs. 4, 5, and 9).

Abstract

The reduction of heptalene diester 1 with diisobutylaluminium hydride (DIBAH) in THF gave a mixture of heptalene-1,2-dimethanol 2a and its double-bond-shift (DBS) isomer 2b (Scheme 3). Both products can be isolated by column chromatography on silica gel. The subsequent chlorination of 2a or 2b with PCl5 in CH2Cl2 led to a mixture of 1,2-bis(chloromethyl)heptalene 3a and its DBS isomer 3b. After a prolonged chromatographic separation, both products 3a and 3b were obtained in pure form. They crystallized smoothly from hexane/Et2O 7 : 1 at low temperature, and their structures were determined by X-ray crystal-structure analysis (Figs. 1 and 2). The nucleophilic exchange of the Cl substituents of 3a or 3b by diphenylphosphino groups was easily achieved with excess of (diphenylphospino)lithium (=lithium diphenylphosphanide) in THF at 0° (Scheme 4). However, the purification of 4a/4b was very difficult since these bis-phosphines decomposed on column chromatography on silica gel and were converted mostly by oxidation by air to bis(phosphine oxides) 5a and 5b. Both 5a and 5b were also obtained in pure form by reaction of 3a or 3b with (diphenylphosphinyl)lithium (=lithium oxidodiphenylphospanide) in THF, followed by column chromatography on silica gel with Et2O. Carboxaldehydes 7a and 7b were synthesized by a disproportionation reaction of the dimethanol mixture 2a/2b with catalytic amounts of TsOH. The subsequent decarbonylation of both carboxaldehydes with tris(triphenylphosphine)rhodium(1+) chloride yielded heptalene 8 in a quantitative yield. The reaction of a thermal-equilibrium mixture 3a/3b with the borane adduct of (diphenylphosphino)lithium in THF at 0° gave 6a and 6b in yields of 5 and 15%, respectively (Scheme 4). However, heating 6a or 6b in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) in toluene, generated both bis-phosphine 4a and its DBS isomer 4b which could not be separated. The attempt at a conversion of 3a or 3b into bis-phosphines 4a or 4b by treatment with t-BuLi and Ph2PCl also failed completely. Thus, we returned to investigate the antipodes of the dimethanols 2a, 2b, and of 8 that can be separated on an HPLC Chiralcel-OD column. The CD spectra of optically pure (M)- and (P)-configurated heptalenes 2a, 2b, and 8 were measured (Figs. 4, 5, and 9).

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Language:English
Date:2010
Deposited On:18 Feb 2011 18:56
Last Modified:05 Apr 2016 14:31
Publisher:Verlag Helvetica Chimica Acta
ISSN:0018-019X
Funders:Swiss National Science Foundation
Publisher DOI:https://doi.org/10.1002/hlca.200900435

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