Disila‐Galaxolide and Derivatives: Synthesis and Olfactory Characterization of Silicon‐Containing Derivatives of the Musk Odorant Galaxolide. Issue 34 (10th July 2013)

• Record Type: Journal Article
• Authors: Dörrich, Steffen; Bauer, Jennifer B.; Lorenzen, Sabine; Mahler, Christoph; Schweeberg, Sarah; Burschka, Christian; Baus, Johannes A.; Tacke, Reinhold; Kraft, Philip
• Is Part Of: Chemistry. Volume 19:Issue 34(2013)
• Page Start: 11396
• Page End: 11408
• Publication Date: 2013-07-10
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201300982
• Languages: English
• ISSNs: 0947-6539

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>A series of silicon‐containing derivatives of the polycyclic musk odorant galaxolide (<bold>4 a</bold>) was synthesized, that is, disila‐galaxolide ((4<italic>RS</italic>, 7<italic>SR</italic>)‐<bold>4 b</bold>/(4<italic>RS</italic>, 7<italic>RS</italic>)‐<bold>4 b</bold>), its methylene derivative <italic>rac</italic>‐<bold>9</bold>, and its <italic>nor</italic> analogue <italic>rac</italic>‐<bold>10</bold>. The tricyclic title compounds with their 7, 8‐dihydro‐6, 8‐disila‐6 <italic>H</italic>‐cyclopenta[<italic>g</italic>]isochromane skeleton were prepared in multistep syntheses by using a cobalt‐catalyzed [2+2+2] cycloaddition of the mono‐ yne H<sub>2</sub>CCHCH<sub>2</sub>OCH<sub>2</sub>CCB(pin) (B(pin)=4, 4, 5, 5‐tetramethyl‐1, 3, 2‐di‐ oxaborolan‐2‐yl) with the diynes H<sub>2</sub>CC[Si(CH<sub>3</sub>)<sub>2</sub>CCH]<sub>2</sub> or H<sub>2</sub>C‐ [Si(CH<sub>3</sub>)<sub>2</sub>CCH]<sub>2</sub> as the key step. Employing [Cr(CO)<sub>3</sub>(MeCN)<sub>3</sub>] as an auxiliary, the disila‐galaxolide diastereomers (4<italic>RS</italic>, 7<italic>SR</italic>)‐<bold>4 b</bold> and (4<italic>RS</italic>, 7<italic>RS</italic>)‐<bold>4 b</bold> could be chromatographically separated through their tricarbonylchromium(0) complexes, followed by oxidative decomplexation. The identity of the title compounds and their precursors was established by elemental analyses and multinuclear NMR spectroscopic studies and in some cases additionally by crystal structure analyses. Compounds (4<italic>RS</italic>, 7<italic>SR</italic>)‐<bold>4 b</bold>, (4<italic>RS</italic>, 7<italic>RS</italic>)‐<bold>4 b</bold>, <italic>rac</italic>‐<bold>9</bold>, and <italic>rac</italic>‐<bold>10</bold> were characterized for their olfactory properties, including GC‐olfactory studies of the racemic compounds on a chiral stationary phase. As for the parent galaxolide stereoisomers <bold>4 a</bold>, only one enantiomer of the silicon compounds (4<italic>RS</italic>, 7<italic>SR</italic>)‐<bold>4 b</bold>, (4<italic>RS</italic>, 7<italic>RS</italic>)‐<bold>4 b</bold>, <italic>rac</italic>‐<bold>9</bold>, and <italic>rac</italic>‐<bold>10</bold>, smelt upon enantioselective GC‐olfactometry, which according to the elution sequence is assumed to be also (4<italic>S</italic>)‐configured as in the case of the galaxolide stereoisomers. The disila‐analogues (4<italic>S</italic>, 7<italic>R</italic>)‐<bold>4 b</bold> and (4<italic>S</italic>, 7<italic>S</italic>)‐<bold>4 b</bold> were, however, about one order of magnitude less intense in terms of their odor threshold than their parent carbon compounds (4<italic>S</italic>, 7<italic>R</italic>)‐<bold>4 a</bold> and (4<italic>S</italic>, 7<italic>S</italic>)‐<bold>4 a</bold>. The introduction of a 7‐methylene group in disila‐galaxolide (<bold>4 b</bold>→<italic>rac</italic>‐<bold>9</bold>) improved the odor threshold by a factor of two. With the novel silicon‐containing galaxolide derivatives, the presumed hydrophobic bulk binding pocket of the corresponding musk receptor(s) could be characterized in more detail, which could be useful for the design of novel musk odorants with an improved environmental profile.</p> </abstract>