General Method for the Synthesis of Isoxazoline N-Oxides from Aliphatic Nitro Compounds

Abstract

A method for the synthesis of isoxazolines N-oxides from primary aliphatic nitro compounds and olefins based on the 1,3-dipolar cycloaddition of intermediate 1-halo-substituted silyl nitronates, followed by halosilane elimination has been described. The nature of the halogen atom plays a key role in determining the stability and reactivity of all intermediates of this process. Bromonitro compounds can be conveniently used in reactions with terminal alkenes, while fluorinated derivatives must be employed for internal olefins.

Key words

aliphatic nitro compounds - silyl nitronates - 1-halo-substituted nitro compounds - 1,3-dipolar cycloaddition

References

• 1a Denmark SE. Thorarensen A. Chem. Rev.  1996,  96:  137 
• 1b Seebach D. Lyapkalo IM. Dahinden R. Helv. Chim. Acta  1999,  82:  1829 
• For recent studies on six-membered nitronates see:
• 1c Tishkov AA. Lesiv AV. Khomutova YA. Strelenko YuA. Nesterov ID. Antipin MYu. Ioffe SL. Denmark SE. J. Org. Chem.  2003,  68:  9477 
• 1d Smirnov VO. Ioffe SL. Tishkov AA. Khomutova YA. Nesterov ID. Antipin MYu. Smit WA. Tartakovsky VA. J. Org. Chem.  2004,  69:  8485 
• 2a Kohler EP. Barrett GR. J. Am. Chem. Soc.  1924,  46:  2105 
• 2b Tartakovsky VA. Gribov BG. Savostianova IA. Novikov SS. Bull. Acad. Sci. USSR, Div. Chem. Sci. (Engl. Transl.)  1965,  14:  1602 
• 2c Clagett M. Gooch A. Graham P. Holy N. Mains B. Strunk J. J. Org. Chem.  1976,  41:  4033 
• 2d Kaji E. Zen S. Chem. Pharm. Bull.  1980,  28:  479 
• 2e Arai N. Narasaka K. Bull. Chem. Soc. Jpn.  1997,  70:  2525 
• 2f Scardovi N. Casalini A. Peri F. Righi P. Org. Lett.  2002,  4:  965 
• 2g Kanemasa S. Yoshimiya T. Wada E. Tetrahedron Lett.  1998,  39:  8869 
• 2h Rosini G. Marotta E. Righi P. Seerden J.-P. J. Org. Chem.  1991,  56:  6258 
• 2i Marotta E. Baravelli M. Maini L. Righi P. Rosini G. J. Org. Chem.  1998,  63:  8235 
• 2j Rosini G. Galarini R. Marotta E. Righi P. J. Org. Chem.  1990,  55:  781 
• 2k Galli C. Marotta E. Righi P. Rosini G. J. Org. Chem.  1995,  60:  6624 
• 2l Gil MV. Roman E. Serrano JA. Tetrahedron Lett.  2000,  41:  3221 
• 2m Falck JR. Yu J. Tetrahedron Lett.  1992,  33:  6723 
• 3 Kunetsky RA. Dilman AD. Ioffe SL. Struchkova MI. Strelenko YA. Tartakovsky VA. Org. Lett.  2003,  5:  4907 
• 4 Frisch MJ. Trucks GW. Schlegel HB. Scuseria GE. Robb MA. Cheeseman JR. Zakrzewski VG. Montgomery JAJr. Stratmann RE. Burant JC. Dapprich S. Millam JM. Daniels AD. Kudin KN. Strain MC. Farkas O. Tomasi J. Barone V. Cossi M. Cammi R. Mennucci B. Pomelli C. Adamo C. Clifford S. Ochterski J. Petersson GA. Ayala PY. Cui Q. Morokuma K. Malick DK. Rabuck AD. Raghavachari K. Foresman JB. Cioslowski J. Ortiz JV. Stefanov BB. Liu G. Liashenko A. Piskorz P. Komaromi I. Gomperts R. Martin RL. Fox DJ. Keith T. Al-Laham MA. Peng CY. Nanayakkara A. Gonzalez C. Challacombe M. Gill PMW. Johnson B. Chen W. Wong MW. Andres JL. Gonzalez C. Head-Gordon M. Replogle ES. Pople JA. Gaussian 98   Gaussian Inc.; Pittsburgh USA: 1998. 
• 6 When this work was in progress, the fluorination of nitro compounds with Selectfluor was reported: Peng W. Shreeve JM. Tetrahedron Lett.  2005,  46:  4905 
• 9 Torssell KBG. Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis   VCH; Weinheim: 1988.  p.45 
• 10 Natsibullin FY. Oreshko GV. Eremenko LT. Izv. Akad. Nauk SSSR, Ser. Khim.  1971,  2344 ; Bull. Acad. Sci. USSR, Div. Chem. Sci. (Engl. Transl.) 1971, 2230
• 11 Takeuchi Y. Nagata K. Koizumi T. J. Org. Chem.  1989,  54:  5453 

5

In a preliminary experiment we observed that the cycloaddition of a 1-chlorosilyl nitronate proceeded slightly faster than that of analogous bromo derivative.

7

The rate of elimination of halosilane from 3-halo-N-silyloxyisoxazolidines depends on many factors such as nature of the halogen and structural features of the heterocyclic ring. For instance, reaction of tert-butyl­-dimethylsilyl nitronate from 1-bromonitroethane with di(methoxycarbonyl)acetylene affords cycloadduct, which does not eliminate bromosilane at room temperature. The mechanism of halosilane elimination is currently under investigation.

8

Upon chromatography adduct 5b decomposed completely, whereas for 5b′ one diasteromer could be isolated.