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DOI: 10.1055/s-2007-980342
Titanium-Mediated Synthesis of Primary Cyclopropylamines from Nitriles and Grignard Reagents
Publikationsverlauf
Publikationsdatum:
23. Mai 2007 (online)
Abstract
This account presents studies on the development of a new method for the preparation of primary cyclopropylamines. The established procedure is simple and the reaction appears to be quite general. A wide range of nitriles and organomagnesium reagents can react to afford diversely substituted cyclopropylamines. Furthermore, bicyclic cyclopropylamines can be obtained via an intramolecular coupling from unsaturated nitriles. The reaction allows an easy preparation of 1-aminocyclopropanecarboxylic acids and 1-azaspirocyclic compounds bearing a cyclopropane ring. The reaction can also be applied to the preparation of polyfunctional and more complex organic molecules as exemplified with the synthesis of carbohydrates bearing aminocyclopropyl moieties and spirocyclopropyl pyrrolidines. During study of the title reaction, an unusual [4+1] cycloaddition reaction to afford cyclopentenylamines or cyclopentenones has been discovered and is described.
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1 Introduction
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2 Direct Synthesis of Cyclopropylamines from Nitriles and Grignard Reagents
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3 Synthesis of Cyclopropylamines via Ligand Exchange
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4 Attempt to Prepare 2-Alkenyl Cyclopropylamines from 1,3-Dienes and Nitriles: An Unusual [4+1] Assembly Reaction
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5 Summary and Outlook
Key words
cyclizations - cyclopropanes - Grignard reagents - nitriles - titanium
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1a
Vilsmaier E. In The Chemistry of the Cyclopropyl GroupRappoport Z. Wiley; New York: 1987. p.1341 -
1b
Houben-Weyl
Vol. E17a-c:
de Meijere A. Thieme; Stuttgart: 1997. - 2
Salaün J. Top. Curr. Chem. 2000, 207: 1 - 3
Wessjohann LA.Brandt W.Thiemann T. Chem. Rev. 2003, 103: 1625 - See for example:
-
4a
Ha JD.Lee J.Blackstock SC.Cha JK. J. Org. Chem. 1998, 63: 8510 -
4b
Williams CM.de Meijere A. J. Chem. Soc., Perkin Trans. 1 1998, 3699 -
4c
Lee HB.Sung MJ.Blackstock SC.Cha JK. J. Am. Chem. Soc. 2001, 123: 11322 -
4d
Campos PJ.Soldevilla A.Sampedro D.Rodriguez MA. Tetrahedron Lett. 2002, 43: 8811 -
4e
Voigt T.Winsel H.de Meijere A. Synlett 2002, 1362 - See for example:
-
5a
Wise R.Andrews JM.Edwards LJ. Antimicrob. Agents Chemother. 1983, 23: 559 -
5b
Todo Y.Nitta J.Miyajima M.Fukuoka Y.Yamashiro Y.Nishida N.Saikawa I.Narita H. Chem. Pharm. Bull. 1994, 42: 2063 -
5c
Brighty KE.Castaldi MJ. Synlett 1996, 1097 -
5d
Högberg M.Sahlberg C.Engelhardt P.Noréen R.Kangasmetsä J.Johansson NG.Öberg B.Vrang L.Zhang H.Sahlberg B.-L.Unge T.Lövgren S.Fridborg K.Bäckbro K. J. Med. Chem. 1999, 42: 4150 -
5e
Daluge SM.Martin MT.Sickles BR.Livingston DA. Nucleosides, Nucleotides Nucleic Acids 2000, 19: 297 - 6
Fujita T. J. Med. Chem. 1973, 16: 923 - 7
Kishner N. J. Russ. Phys. Chem. Ges. 1901, 33: 377 - For recent syntheses of aminocyclopropane derivatives, see:
-
8a
Adams LA.Aggarwal VK.Bonnert RV.Bressel B.Cox RJ.Shepherd J.deVicente J.Walter M.Whittingham WG.Winn CL. J. Org. Chem. 2003, 68: 9433 -
8b
Bégis G.Cladingboel D.Motherwell WB. Chem. Commun. 2003, 2656 -
8c
Wurz RP.Charette AB. J. Org. Chem. 2004, 69: 1262 -
8d
Moreau B.Charette AB. J. Am. Chem. Soc. 2005, 127: 18014 -
8e
Díez D.García P.Fernández P.Marcos IS.Garrido NM.Basabe P.Broughton HB.Urones JG. Synlett 2005, 158 -
8f
Hohn E.Pietruszka J.Solduga G. Synlett 2006, 1531 -
9a
Chaplinski V.de Meijere A. Angew. Chem., Int. Ed. Engl. 1996, 35: 413 -
9b
de Meijere A.Kozhushkov SI.Savchenko AI. J. Organomet. Chem. 2004, 689: 2033 -
10a
Kulinkovich OG.de Meijere A. Chem. Rev. 2000, 100: 2789 -
10b
de Meijere A.Koshushkov SI.Savchenko AI. In Titanium and Zirconium in Organic SynthesisMarek I. Wiley-VCH; Weinheim, Germany: 2002. p.390 -
11a
Kulinkovich OG.Sviridov SV.Vasilevsky DA.Pritytskaja TS. J. Org. Chem. USSR 1989, 25: 2027 ; Zh. Org. Khim. 1989, 25, 2244 -
11b
Kulinkovich OG.Sviridov SV.Vasilevsky DA. Synthesis 1991, 234 -
11c
Kulinkovich O. Eur. J. Org. Chem. 2004, 4517 - 12
Bertus P.Szymoniak J. Chem. Commun. 2001, 1792 -
15a
Bertus P.Gandon V.Szymoniak J. Chem. Commun. 2000, 171 -
15b
Gandon V.Bertus P.Szymoniak J. Eur. J. Org. Chem. 2000, 3713 -
15c
Szymoniak J.Bertus P. Top. Organomet. Chem. 2005, 10: 107 - 17 Simple nitriles do not undergo double alkylation by alkyl Grignard reagents. The Ti(Oi-Pr)4-mediated double alkylation of protected cyanohydrins have been reported, see:
Charette AB.Gagnon A.Janes M.Mellon C. Tetrahedron Lett. 1998, 39: 5147 - 18
Bertus P.Szymoniak J. J. Org. Chem. 2002, 67: 3965 - 19 Similar chelation-promoted addition of Grignard reagents to α-alkoxy imines has been reported, see:
Franz T.Hein M.Veith U.Jäger V.Peters E.-M.Peters K.von Schnering HG. Angew. Chem., Int. Ed. Engl. 1994, 33: 1298 - 20
Bertus P.Szymoniak J. J. Org. Chem. 2003, 68: 7133 - 21
Wiedemann S.Frank D.Winsel H.de Meijere A. Org. Lett. 2003, 5: 753 -
22a
Aufranc P.Ollivier J.Stolle A.Bremer C.Es-Sayed M.de Meijere A.Salaün J. Tetrahedron Lett. 1993, 34: 4193 -
22b
Racouchot S.Ollivier J.Salaün J. Synlett 2000, 1729 - 23 Naturally occurring ACC is the precursor of ethylene, a phytohormone responsible for fruit ripening, see:
Pirrung MC. Acc. Chem. Res. 1999, 32: 711 - For the biological activity and the synthesis of these important series of compounds, see:
-
24a
Alami A.Calmes M.Daunis J.Jacquier R. Bull. Soc. Chim. Fr. 1993, 130: 5 -
24b
Burgess K.Ho K.-K.Moye-Sherman D. Synlett 1994, 575 -
25a Coronamic acid is the constituent of the bacterial toxin coronatine in Pseudomonas coronafacience var. atropurpurea; see:
Ichiara A.Shiraishi K.Sato H.Sakamura S.Nishiyama K.Sakai R.Furusaki A.Matsumoto T. J. Am. Chem. Soc. 1977, 99: 636 -
25b
allo-Coronamic acid is a competitive inhibitor of the ethylene biosynthesis, producing 1-butene; see:
Hoffman NE.Yang SF.Ichiara A.Sakamura S. Plant Physiol. 1982, 70: 195 - 26 Benzyloxyacetonitrile can be obtained in one step from sodium cyanide, formaldehyde and benzyl cyanide, see:
Kachinsky JLC.Salomon RG. J. Org. Chem. 1986, 51: 1393 - 27
Bertus P.Szymoniak J. Synlett 2003, 265 - 28 For a review on β-aminocarboxylic acids containing a cyclopropane ring, see:
Gnad F.Reiser O. Chem. Rev. 2003, 103: 1603 - 29
Laroche C.Harakat D.Bertus P.Szymoniak J. Org. Biomol. Chem. 2005, 3: 3482 - 31
Seebach D.Beck A.Heckel A. Angew. Chem. Int. Ed. 2001, 40: 92 - 32
Laroche C.Behr JB.Szymoniak J.Bertus P.Plantier-Royon R. Eur. J. Org. Chem. 2005, 5084 - 33
Laroche C.Plantier-Royon R.Szymoniak J.Bertus P.Behr J.-B. Synlett 2006, 223 - 34
Laroche C.Behr J.-B.Szymoniak J.Bertus P.Schütz C.Vogel P.Plantier-Royon R. Bioorg. Med. Chem. 2006, 14: 4047 - 35 The ligand exchange of alkenes on titanacyclopropanes was first described by Kulinkovich et al., see:
Kulinkovich OG.Savchenko AI.Sviridov SV.Vasilevski DA. Mendeleev Commun. 1993, 230 - 36
Sato F.Urabe H.Okamoto S. Chem. Rev. 2000, 100: 2835 -
37a
Lee J.Kang CH.Kim H.Cha JK. J. Am. Chem. Soc. 1996, 118: 291 -
37b
U JS.Lee J.Cha JK. Tetrahedron Lett. 1997, 38: 5233 -
37c
Lee J.Cha JK. J. Org. Chem. 1997, 62: 1584 -
38a
Kasatkin A.Sato F. Tetrahedron Lett. 1995, 36: 6079 -
38b
Okamoto S.Iwakubo M.Kobayashi K.Sato F. J. Am. Chem. Soc. 1997, 119: 6984 -
39a
de Meijere A.Williams CM.Kourdioukov A.Sviridov SV.Chaplinski V.Kordes M.Savchenko AI.Stratmann C.Noltemeyer M. Chem. Eur. J. 2002, 8: 3789 -
39b
Gensini M.Kozhushkov SI.Yufit D.Howard JAK.Es-Sayed M.de Meijere A. Eur. J. Org. Chem. 2002, 2499 - 40
Laroche C.Bertus P.Szymoniak J. Tetrahedron Lett. 2003, 44: 2485 - 41
Laroche C. PhD Dissertation Université de Reims; France: 2006. - 42 (i-PrO)2Ti(i-Pr)2, generated from i-PrMgCl and Ti(Oi-Pr)4, has been demonstrated to undergo β-fragmentation at particularly low temperature (ca -50 °C), see:
Sato F.Urabe H.Okamoto S. Pure Appl. Chem. 1999, 71: 1511 - 43
Williams CM.Chaplinski V.Schreiner PR.de Meijere A. Tetrahedron Lett. 1998, 39: 7695 - 44
Laroche C.Bertus P.Szymoniak J. Chem. Commun. 2005, 3030 - For the synthetic uses of titanacyclopentenes, see:
-
45a
Urabe H.Mitsui K.Ohta S.Sato F. J. Am. Chem. Soc. 2003, 125: 6074 -
45b
Goeke A.Mertl D.Jork S. Chem. Commun. 2004, 166 - 47 The [4+1] methodology was recently applied to some other esters, see:
Baraut J.Perrier A.Comte V.Richard P.Le Gendre P.Moïse C. Tetrahedron Lett. 2006, 47: 8319 - See for example:
-
48a
Eaton BE.Rollman B. J. Am. Chem. Soc. 1992, 114: 6245 -
48b
Franck-Neumann M.Michelotti EL.Simler R.Vernier J.-M. Tetrahedron Lett. 1992, 33: 7361 -
48c
Sierra MA.Soderberg B.Lander PA.Hegedus LS. Organometallics 1993, 12: 3769 -
48d
Negishi E.-i.Ma S.Amanfu J.Copéret C.Miller JA.Tour JM. J. Am. Chem. Soc. 1996, 118: 5919 -
48e
Barluenga J.Lopéz S.Flórez J. Angew. Chem. Int. Ed. 2003, 42: 231 -
48f
Gagnier SV.Larock RC. J. Am. Chem. Soc. 2003, 125: 4804
References and Notes
Bertus, P.; Szymoniak, J., unpublished results.
14The intermediacy of C was demonstrated by deuterolysis.
16Attempts to perform the aminocyclopropanation reaction by using Cp2Zr(ethylene) led to complex reaction mixtures.
30The introduction of EtMgBr to a mixture of 61 and 0.2 equiv of Ti(Oi-Pr)4 in Et2O over a 1, 15, or 30 min period led, respectively, to a 19%, 40%, or 55% yield of 55.
46The yield of 94 decreased rapidly at temperatures higher than 0 °C, due to the instability of the complex J.