Methoxydioxasilepane: A Versatile and Stable Synthetic Precursor of Trimethoxysilane

Abstract

This study introduces aryl(methoxy)dioxasilepane as a versatile and stable precursor for aryl(trimethoxy)silanes. We conducted a quantitative assessment of the stability of this silicon moiety under acidic and basic conditions, demonstrating its superior stability compared to triethoxysilane, and methyl- or (trifluoroethoxy)dioxasilepanes. The synthetic utility of the methoxydioxasilepane unit was further elucidated through an examination of its orthogonality and selective functionalization capabilities. Notably, we developed an efficient method for the conversion of methoxydioxasilepane into trimethoxysilane. This method underscores the potential of a methoxydioxasilepane as a surrogate in multistep syntheses of silanetriols, which offer advantages in the development of silicon-based bioisosteres for medicinal chemistry applications.

Key words

silanols - silanetriols - alkoxysilanes - bioisosteres - dioxasilepanes

Publication History

Received: 04 July 2024

Accepted after revision: 02 September 2024

Accepted Manuscript online:
02 September 2024

Article published online:
26 September 2024

• References

• 1a Tacke R, Zilch H. Endeavour 1986; 10: 191
• 1b Pooni PK, Showell GA. Mini-Rev. Med. Chem. 2006; 6: 1169
• 1c Meanwell NA. J. Med. Chem. 2011; 54: 2529
• 1d Tacke R, Dörrich S. In Atypical Elements in Drug Design, Vol. 17. Schwarz J. Springer; Cham: 2014: 29
• 1e Fujii S, Hashimoto Y. Future Med. Chem. 2017; 9: 485
• 1f Ramesh R, Reddy DS. J. Med. Chem. 2018; 61: 3779
• 2a Yamagishi H, Shimokawa J, Yorimitsu H. ACS Catal. 2023; 13: 7472
• 2b Hardman-Baldwin AM, Mattson AE. In Science of Synthesis Knowledge Updates 2017, Vol. 1. Joule JA, Krause N, Oestreich M, Rademann J, Schaumann E, Wirth T. Thieme; Stuttgart: 2017: 213-245
• 3a Sieburth SM, Nittoli T, Mutahi AM, Guo L. Angew. Chem. Int. Ed. 1998; 37: 812
• 3b Chen C.-A, Sieburth SM, Glekas A, Hewitt GW, Trainor GL, Erickson-Viitanen S, Garber SS, Cordova B, Jeffry S, Klabe RM. Chem. Biol. 2001; 8: 1161
• 3c Mutahi M. w, Nittoli T, Guo L, Sieburth SM. J. Am. Chem. Soc. 2002; 124: 7363
• 3d Sieburth SM, Chen C.-A. Eur. J. Org. Chem. 2006; 311
• 3e Hernández D, Mose R, Skrydstrup T. Org. Lett. 2011; 13: 732
• 3f Madsen JL. H, Andersen TL, Santamaria S, Nagase H, Enghild JJ, Skrydstrup T. J. Med. Chem. 2012; 55: 7900
• 3g Min GK, Hernández D, Skrydstrup T. Acc. Chem. Res. 2013; 46: 457
• 4 Saito H, Shimokawa J, Yorimitsu H. Chem. Sci. 2021; 12: 9546
• 5 Hitoshio K, Maeda H, Teranishi K, Shimokawa J, Yorimitsu H. Chem. Commun. 2024; 60: 7339
• 6a Krempner C. Eur. J. Inorg. Chem. 2011; 1689
• 6b Jeon M, Han J, Park J. ACS Catal. 2012; 2: 1539
• 6c Pietschnig R, Spirk S. Coord. Chem. Rev. 2016; 323: 87
• 6d Pietschnig R. In Main Group Strategies towards Functional Hybrid Materials . Baumgartner T, Jäkle F. John Wiley & Sons Ltd; Hoboken: 2018: 141
• 7 Curley K, Pratt RF. J. Am. Chem. Soc. 1997; 119: 1529
• 8 Blunder M, Hurkes N, Spirk S, List M, Pietschnig R. Bioorg. Med. Chem. Lett. 2011; 21: 363
• 9 Murata M, Ishikura M, Nagata M, Watanabe S, Masuda Y. Org. Lett. 2002; 4: 1843
• 10a Tyler LJ. J. Am. Chem. Soc. 1955; 77: 770
• 10b Andrianov KA, Zhdanov AA, Morgunova EF. Zh. Obshch. Khim. 1957; 27: 156
• 10c Takiguchi T. J. Am. Chem. Soc. 1959; 81: 2359
• 10d Lapkin II, Povarnitsina TN. Zh. Obshch. Khim. 1964; 34: 1202
• 10e Michalska Z, Lasocki Z. Bull. Acad. Pol. Sci., Ser. Sci. Chim. 1971; 19: 757
• 10f Ishida H, Koenig JL. J. Polym. Sci., Polym. Phys. Ed. 1979; 17: 1807
• 10g Damja RI, Eaborn C. J. Organomet. Chem. 1985; 290: 267
• 10h Al-Juaid SS, Buttrus NH, Damja RI, Derouiche Y, Eaborn C, Hitchcock PB, Lickiss PD. J. Organomet. Chem. 1989; 371: 287
• 10i Chandrasekhar V, Boomishankar R, Nagendran S. Chem. Rev. 2004; 104: 5847
• 11 Ackermann L, Althammer A. Org. Lett. 2006; 8: 3457