A Mild One-Pot Conversion of Alkenes into Amines through Tandem Ozonolysis and Reductive Amination

Abstract

The selective reduction of hydroperoxyacetals to aldehydes by sodium triacetoxyborohydride provides the basis for a mild one-pot synthesis of amines from alkenes.

ozonolysis - hydroperoxyacetal - reductive amination - amine - sodium triacetoxyborohydride

References

<A NAME="RM64811SS-1">1</A>

These authors contributed equally to this manuscript.

<A NAME="RM64811SS-2A">2a</A> Margaretha P. In Science of Synthesis   Vol. 40a:  Schaumann E. Enders D. Thieme; Stuttgart: 2009.  p.65-89  

<A NAME="RM64811SS-2B">2b</A> Baxter EW. Reitz AB. Org. React.  2002,  59:  1 

<A NAME="RM64811SS-2C">2c</A> Ghosh AK. Bilcer G. Schiltz G. Synthesis  2001,  2203 

<A NAME="RM64811SS-3">3</A> Van Ornum SG. Champeau RM. Pariza R. Chem. Rev.  2006,  106:  2990 

Although a variety of reagents have been applied for post-ozonolysis reductions, most examples employ Me₂S, Ph₃P, thiourea, or Zn/AcOH:

<A NAME="RM64811SS-4A">4a</A> Kropf H. In Houben-Weyl Methoden der Organischen Chemie, Peroxo-Verbindungen   Kropf H. Thieme; Stuttgart: 1988.  p.1102-1116  

<A NAME="RM64811SS-4B">4b</A> The reduction of ozonides, tetraoxanes, or polymeric peroxides derived from hindered substrates can be very slow, leading to the inadvertent concentration of potentially explosive intermediates, see, for example: Chen L. Wiemer DF. J. Org. Chem.  2002,  67:  7561 

<A NAME="RM64811SS-4C">4c</A> Lavalle P. Bouthillier G. J. Org. Chem.  1986,  51:  1362 

<A NAME="RM64811SS-4D">4d</A> Hida T. Kikuchi J. Kakinuma M. Nogusa H. Org. Process Res. Dev.  2010,  14:  1493 

<A NAME="RM64811SS-4E">4e</A> Gordon PM. Chem. Eng. News  1990,  68 (32):  2 

<A NAME="RM64811SS-5A">5a</A> Fisher TJ. Dussault PH. Tetrahedron Lett.  2010,  51:  5615 

<A NAME="RM64811SS-5B">5b</A> Schiaffo CE. Dussault PH. J. Org. Chem.  2008,  73:  4688 

<A NAME="RM64811SS-5C">5c</A> Schwartz C. Raible J. Mott K. Dussault PH. Tetrahedron  2006,  62:  10747 

<A NAME="RM64811SS-6A">6a</A> Abdel-Magid AF. Mehrman SJ. Org. Process Res. Dev.  2006,  10:  971 

<A NAME="RM64811SS-6B">6b</A> Abdel-Magid AF. Carson KC. Harris BD. Maryanoff CA. Shah RD. J. Org. Chem.  1996,  61:  3849 

<A NAME="RM64811SS-6C">6c</A> Gribble G. Chem. Soc. Rev.  1998,  27:  395 

<A NAME="RM64811SS-6D">6d</A> Matos K. Pichlmair S. Burkhardt ER. Chim. Oggi.  2007,  25:  17 

<A NAME="RM64811SS-7">7</A> Lane CF. Synthesis  1975,  135 

For reductive aminations involving NaCNBH₃ and hydroperoxyacetals or related intermediates, see:

<A NAME="RM64811SS-8A">8a</A> Namba K. Murata Y. Horikawa M. Iwashita T. Kusumoto S. Angew. Chem. Int. Ed.  2007,  46:  7060 

<A NAME="RM64811SS-8B">8b</A> Shawe TT. Sheils CJ. Gray SM. Conard JL. J. Org. Chem.  1994,  59:  5841 

<A NAME="RM64811SS-8C">8c</A> Kawaguchi M. Hayashi O. Sakai N. Hamada M. Yamamoto Y. Oda J. Agric. Biol. Chem.  1986,  50:  3107 

<A NAME="RM64811SS-9">9</A> Ozonides react with NaCNBH₃ very slowly, as evidenced by the selective reduction of a ketone in the presence of an ozonide: Laventine DM. Davies M. Evinson EL. Jenkins PR. Cullis PM. Fawcett J. Tetrahedron Lett.  2005,  46:  307 

<A NAME="RM64811SS-10">10</A> Ozonides derived from mono- and 1,1-disubstituted alkenes can react with secondary amines to form tertiary amines through base-promoted E₁cb fragmentation to form an aldehyde, which undergoes reductive amination in the presence of the cogenerated formate: Hon Y.-S. Lu L. Tetrahedron Lett.  1993,  34:  5309 

Reductive amination of ozonides and/or hydroperoxyacetals has been accomplished using more powerful reducing systems; Raney Ni:

<A NAME="RM64811SS-11A">11a</A> Pollart KA. Miller RE. J. Org. Chem.  1962,  27:  2392 

<A NAME="RM64811SS-11B">11b</A> Diaper DGM. Mitchell DL. Can. J. Chem.  1962,  40:  1189 

<A NAME="RM64811SS-11C">11c</A> White RW. King SW. O’Brien JL. Tetrahedron Lett.  1971,  3591 

Pt/H₂:

<A NAME="RM64811SS-11D">11d</A> Brooks PR. Caron S. Coe JW. Ng KK. Singer RA. Vazquez E. Vetelino MG. Watson HH. Whritenour DC. Wirtz MC. Synthesis  2004,  1755 

NaBH₄:

<A NAME="RM64811SS-11E">11e</A> Mustafin AG. Dyachenko DI. Gataullin RR. Ishmuratov GYu. Kharisov RYa. Abdrakhmanov IB. Tolstikov GA. Russ. Chem. Bull.  2003,  52:  989 

<A NAME="RM64811SS-12A">12a</A> Noe MC. Hawkins JM. Snow SL. Wolf-Gouveia L. J. Org. Chem.  2008,  73:  3295 

<A NAME="RM64811SS-12B">12b</A> Yang L. Butora G. Jiao RX. Pasternak A. Zhou C. Parsons WH. Mills SG. Vicario PP. Ayala JM. Cascieri MA. MacCoss M. J. Med. Chem.  2007,  50:  2609 

<A NAME="RM64811SS-13">13</A> NaBH(OAc)₃ has been reported to reduce ozonolysis products to the corresponding alcohols: Ishmuratov GYu. Kharisov RYa. Yakovleva MP. Botsman OV. Muslukhov RR. Tolstikov GA. Russ. J. Org. Chem.  2001,  37:  37 

<A NAME="RM64811SS-14A">14a</A> Bunnelle WH. Chem. Rev.  1991,  91:  335 

<A NAME="RM64811SS-14B">14b</A> Zmitek K. Zupan M. Iskra J. Org. Biomol. Chem.  2007,  5:  3895 

<A NAME="RM64811SS-15">15</A>

All products were purified by flash chromatography to greater than 95% purity (NMR). Hydroperoxides were characterized by ^¹H/^¹³C NMR; aldehydes and amines were characterized by ^¹H/^¹³C NMR, IR, and HRMS.

<A NAME="RM64811SS-16">16</A> Smith LL. Hill FL. J. Chromatogr.  1972,  66:  101