Iron-Catalyzed Reductive Metalation–Allylation and Metalative Cyclization of 2,3-Disubstituted Oxetanes and Their Stereoselectivity

Abstract

A novel process for the reductive magnesiation of 2-substituted oxetanes and the metalative cyclization of ω-alkynyl oxetanes is developed using n-propylmagnesium chloride in the presence of an iron catalyst. The generated intermediate organomagnesium compounds react with electrophiles. The reactions of 2,3-disubstituted oxetanes and their subsequent allylation with allyl halides in the presence or absence of copper(I) cyanide as the catalyst is studied with a unique switching of stereoselectivity being observed in the absence or presence of copper(I) cyanide . In addition, it is found that the metalative cyclization of 3-substituted 2-alkynyl oxetanes proceeds in an anti-selective manner starting from both syn- and anti-substrates. In all cases, the stereochemistry at the 2-position of the oxetanes is lost during the reactions suggesting the involvement of a radical process.

Key words

iron catalyst - oxetanes - reductive magnesiation - metalative cyclization - (3-oxidopropyl)magnesium - diastereoselective reaction

• References

• 1 Sugiyama Y, Heigozono S, Okamoto S. Org. Lett. 2014; 16: 6278

For Fe-catalyzed Csp³–O bond cleavage and subsequent Csp³–Csp³ bond formation, see:
• 2a Fan X, Cui X.-M, Guan Y.-H, Fu L.-A, Lv H, Guo K, Zhu H.-B. Eur. J. Org. Chem. 2014; 498
• 2b Hilt G, Bolze P, Kieltsch I. Chem. Commun. 2005; 1996

For examples of Fe-catalyzed C–O bond cleavage reactions, see:
• 2c Li B.-J, Xu L, Wu Z.-H, Guan B.-T, Sun C.-L, Wang B.-Q, Shi Z.-J. J. Am. Chem. Soc. 2009; 131: 14656
• 2d Dieskau AP, Plietker B. Org. Lett. 2011; 13: 5544
• 2e Gärtner D, Konnerth H, Jacobi von Wangelin A. Catal. Sci. Technol. 2013; 3: 2541
• 2f Silberstein AL, Ramgren SD, Garg N. Org. Lett. 2012; 14: 3796
• 2g Agrawal T, Cook SP. Org. Lett. 2013; 15: 96

For a Mn-catalyzed reaction, see:
• 2h He R, Jin X, Chen H, Huang Z.-T, Zheng Q.-Y, Wang C. J. Am. Chem. Soc. 2014; 136: 6558
• 3 Gupta V, Sudhir VS, Mandal T, Schneider C. Angew. Chem. Int. Ed. 2012; 51: 12609
• 4 Landa A, Maestro M, Masdeu C, Puente A, Vera S, Oiarbide M, Palomo C. Chem. Eur. J. 2009; 15: 1562
• 5 Hoffmann RW, Hölzer B. Chem. Commun. 2001; 491
• 6 Hoffmann RW, Hölzer B. J. Am. Chem. Soc. 2002; 124: 4204
• 7 Elongation of the reaction time for anti-6b after consumption of the substrate did not affect the diastereomeric ratio of the product 8b.
• 8a Diastereoisomers of 2-[2-methyl-5-(propan-2-ylidene)cy­-clopentyl]propan-1-ol: Hacini S, Santelli M. Tetrahedron 1989; 45: 6449
• 8b Diastereoisomers of 2-[2-(hydroxymethyl)-3-methylcyclopentyl]propan-1-ol: Schöllhorn B, Mulzer J. Eur. J. Org. Chem. 2006; 901
• 8c Takeda K, Toyota M. Heterocycles 2012; 84: 1271
• 9a Weidenbruch M, Piel H. Organometallics 1994; 13: 3990
• 9b Cámpora J, del Mar Conejo M, Mereiter K, Palma P, Pérez C, Reyes ML, Ruiz C. J. Organomet. Chem. 2003; 683: 220
• 9c Saino N, Kogure D, Kase K, Okamoto S. J. Organomet. Chem. 2006; 691: 3129