A Perspective on the Stereodefined N,O-Acetals: Synthesis and Potential Applications

Abstract

Developing chemical reactions that rapidly introduce molecular diversity in a controlled manner represents a prime goal in synthetic organic chemistry. In this regard, our recent studies on the asymmetric synthesis and utilization of stereodefined N,O-acetal opens up a conceptually new methodology. The synthesis of labile N,O-acetals was accomplished by highly efficient and chemoselective Pd-catalyzed asymmetric hydroamination of alkoxyallenes. Furthermore, the utility of the stereodefined N,O-acetals as a stereodiversity-generating element was established by the gold-catalyzed cycloisomerization. In addition to these results, new aspects of the N,O-acetals as diversity-generating elements are also discussed.

Key words

hydroamination - allenes - N,O-acetal - piperidines - diversity

• References

• 1 For a review on N,O-acetals, see: Warriner S. Category 4: Compounds with Two Carbon-Heteroatom Bonds. In Science of Synthesis. Vol. 30. Bellus D. Thieme; Stuttgart: 2007: 7

For selected examples on the use of nonallylic N,O-acetals as iminium ion precursors, see:
• 2a Bates RW, Boonsombat J, Lu Y, Nemeth JA, Sa-Ei K, Song P, Cai MP, Cranwell PB, Winbush S. Pure Appl. Chem. 2008; 80: 681 ; and references cited therein
• 2b Fleming JJ, Fiori KW, Du Bois J. J. Am. Chem. Soc. 2003; 125: 2028
• 2c Kamatani A, Overman LE. Org. Lett. 2001; 3: 1229
• 2d Harding KE, Coleman MT, Liu LT. Tetrahedron Lett. 1991; 32: 3795
• 3a Yamamoto Y, Nakada T, Nemoto H. J. Am. Chem. Soc. 1992; 114: 121
• 3b Roos EC, Mooiweer HH, Hiemstra H, Speckamp WN, Kaptein B, Boesten WH. J, Kamphuis J. J. Org. Chem. 1992; 57: 6769

For selected examples for the nonstereoselective synthesis of N,O-acetals, see:
• 4a Ko CH, Hsung RP. Org. Biomol. Chem. 2007; 5: 431
• 4b Kiren S, Ning SG, Williams LJ. Tetrahedron Lett. 2007; 48: 7456
• 4c Wan S, Green ME, Park J.-H, Floreancig PE. Org. Lett. 2007; 9: 5385
• 4d Harayama Y, Yoshida M, Kamimura D, Wada Y, Kita Y. Chem.–Eur. J. 2006; 12: 4893
• 4e See also ref. 2b
• 5a Kobayashi T, Hasegawa F, Hirose Y, Tanaka K, Mori H, Katsumura S. J. Org. Chem. 2012; 77: 1812
• 5b Groaning MD, Meyers AI. Tetrahedron 2000; 56: 9843 ; and references cited therein
• 6 Li G, Fronczek FR, Antilla JC. J. Am. Chem. Soc. 2008; 130: 12216
• 7 Vellalath S, Čorić I, List B. Angew. Chem. Int. Ed. 2010; 49: 9749
• 8 Honjo T, Phipps RJ, Rauniyar V, Toste FD. Angew. Chem. Int. Ed. 2012; 51: 9684

For the synthesis and utility of nonstereodefined allylic N,O-acetals, see:
• 9a Kinderman SS, Wekking MM. T, van Maarseveen JH, Schoemaker HE, Hiemstra H, Rutjes FP. J. T. J. Org. Chem. 2005; 70: 55
• 9b Kinderman SS, de Gelder R, van Maarseveen JH, Schoemaker HE, Hiemstra H, Rutjes FP. J. T. J. Am. Chem. Soc. 2004; 126: 4100
• 9c Kinderman SS, Doodeman R, van Beijma JW, Russcher JC, Tjen KC. M. F, Kooistra TM, Mohaselzadeh H, van Maarseveen JH, Hiemstra H, Schoemaker HE, Rutjes FP. J. T. Adv. Synth. Catal. 2002; 344: 736

For selected examples on the racemic intermolecular hydroamination of allenes, see:
• 10a Zeng X, Soleilhavoup M, Bertrand G. Org. Lett. 2009; 15: 3166
• 10b Kinder RE, Zhang Z, Widenhoefer RA. Org. Lett. 2008; 10: 3157
• 10c Wang ZJ, Benitez D, Tkatchouk E, Goddard IiiW. A, Toste FD. J. Am. Chem. Soc. 2010; 132: 13064
• 10d Desarbre E, Merour JY. Tetrahedron Lett. 1996; 37: 43
• 10e Donohoe TJ, Orr AJ, Gosby K, Bingham M. Eur. J. Org. Chem. 2005; 1969
• 10f Donohoe TJ, Kershaw NM, Orr AJ, Wheelhouse KM. P, Fishlock LP, Lacy AR, Bingham M, Procopiou PA. Tetrahedron 2008; 64: 809

For selected examples of other metal-catalyzed hydroaminations, see:
• 11a Liu Z, Yamamichi H, Madrahimov ST, Hartwig JF. J. Am. Chem. Soc. 2011; 133: 2772
• 11b Stubbert BD, Marks TJ. J. Am. Chem. Soc. 2007; 129: 6149
• 11c Ackermann L, Bergman RG, Loy RN. J. Am. Chem. Soc. 2003; 125: 11956
• 11d Grigg R, Sridharan V, Xu LH. J. Chem. Soc., Chem. Commun. 1995; 1903

For recent examples on the intramolecular asymmetric hydroamination of allenes, see:
• 12a LaLonde RL, Wang ZJ, Mba M, Lackner AD, Toste FD. Angew. Chem. Int. Ed. 2010; 49: 59
• 12b LaLonde RL, Sherry BD, Kang EJ, Toste FD. J. Am. Chem. Soc. 2007; 129: 2452
• 12c Zhang Z, Bender CF, Widenhoefer RA. J. Am. Chem. Soc. 2007; 129: 14148
• 13 Kim H, Rhee YH. J. Am. Chem. Soc. 2012; 134: 4011
• 14a Trost BM, Xie J, Sieber JD. J. Am. Chem. Soc. 2011; 133: 20611
• 14b Trost BM, Simas AB. C, Plietker B, Jakel C, Xie J. Chem.–Eur. J. 2005; 11: 7075
• 14c Kamijo S, Yamamoto Y. Tetrahedron Lett. 1999; 40: 1747

For recent reviews on the Pd-catalyzed allylic alkylation, see:
• 15a Trost BM, Zhang T, Sieber JD. Chem. Sci. 2010; 1: 427
• 15b Trost BM, Fandrick DR. Aldrichimica Acta 2007; 40: 59
• 16 Kim C, Bae HJ, Lee JH, Jeong W, Kim H, Sampath V, Rhee YH. J. Am. Chem. Soc. 2009; 131: 14660

For recent reviews on gold-catalyzed reactions, see:
• 17a Corma A, Leyva-Pérez A, Sabater MJ. Chem. Rev. 2011; 111: 1657
• 17b Fürstner A. Chem. Soc. Rev. 2009; 38: 3208
• 17c Gorin DJ, Sherry BD, Toste FD. Chem. Rev. 2008; 108: 3351
• 17d Hashmi AS. K. Chem. Rev. 2007; 107: 3180

For selected examples involving stereochemical transfer from sp³-hybridized compounds in gold-catalyzed reactions, see:
• 18a Aponick A, Biannic B. Org. Lett. 2011; 13: 1330
• 18b Kawai N, Abe R, Matsuda M, Uenishi J. J. Org. Chem. 2011; 76: 2012
• 18c Mukherjee P, Widenhoefer RA. Org. Lett. 2010; 12: 1184
• 18d Nakamura I, Sato T, Terada M, Yamamoto Y. Org. Lett. 2008; 10: 2649
• 18e Dubé P, Toste FD. J. Am. Chem. Soc. 2006; 128: 12062
• 19 Shin D.-Y, Jung J.-K, Seo S.-Y, Lee Y.-S, Paek S.-M, Chung YK, Shin DM, Suh Y.-G. Org. Lett. 2003; 5: 3635

For recent examples on the diversity-oriented synthesis of piperidine compounds, see:
• 20a Ying Y, Kim H, Hong J. Org. Lett. 2011; 13: 796
• 20b Smith AB, Han H, Kim W.-S. Org. Lett. 2011; 13: 3328