Subscribe to RSS
DOI: 10.1055/s-2004-822889
Carbon-Carbon Bond Construction Based on Radical Addition to C=N Bond
Publication History
Publication Date:
25 March 2004 (online)
![](https://www.thieme-connect.de/media/synlett/200407/lookinside/thumbnails/10.1055-s-2004-822889-1.jpg)
Abstract
We have studied the carbon radical addition to imine derivatives as an effective carbon-carbon bond forming method for the synthesis of a variety of amines. The reaction of oxime ethers proceeded smoothly in the presence of BF3·OEt2 to give the alkylated products in high yields via the free radical-mediated carbon-carbon bond forming process. Intermolecular radical addition to oxime ethers was effectively improved by using alkyl iodides and triethylborane, which acts multiply as a Lewis acid, a radical initiator and a terminator. The asymmetric synthesis of α-amino acids based on a diastereoselective radical addition to glyoxylic imine derivatives was achieved. Highly diastereoselective alkyl radical addition to Oppolzer’s camphorsultam derivatives of oxime ether provided a convenient method for preparing the enantiomerically pure α,β-dialkyl-β-amino acids. We have demonstrated that imine derivatives such as oxime ethers, hydrazones, and nitrones are excellent radical acceptors for the radical reactions in aqueous medium. The radical addition to imine derivatives in aqueous medium was also studied by using indium or zinc as a single-electron transfer radical initiator. We have found that triethylborane can be applied to solid-phase radical reactions. The solid-phase tandem carbon-carbon bond forming reaction of oxime ethers connected with an α,β-unsaturated carbonyl group proceeded effectively to give the azacycles or chiral oxacycles after cleavage from the resin.
-
1 Introduction
-
2 Intermolecular Radical Addition to Imine Derivatives
-
2.1 Addition to Oxime Ethers
-
2.2 Reactivity of Imine Derivatives
-
2.3 Iodine Atom-Transfer Reaction
-
3 Stereocontrol in Radical Addition to Imine Derivatives
-
3.1 Addition to Chiral Glyoxylic Oxime Ether
-
3.2 Addition to Chiral Unactivated Oxime Ether
-
3.3 Addition to Chiral Nitrone
-
4 Radical Reaction of Imine Derivatives in Aqueous Media
-
4.1 One-Pot Reaction
-
4.2 Triethylborane-Mediated Reaction in Aqueous Media
-
4.3 Zinc-Mediated Reaction in Aqueous Media
-
5 Solid-Phase Radical Reaction
-
5.1 Intermolecular Radical Reaction
-
5.2 Intramolecular Radical Reaction
-
5.3 Tandem Radical Addition-Cyclization
-
5.4 Solid-Phase Radical Reaction in Aqueous Media
-
6 Conclusion
Key words
radical - imine - oxime ether - amino acid - water - solid-phase - hydrazone - nitrone
-
1a
Fossey J.Lefort D.Sorba J. Free Radicals in Organic Chemistry John Wiley & Sons; New York: 1995. -
1b
Ryu I.Sonoda N.Curran DP. Chem. Rev. 1996, 96: 177 -
1c
Snider BB. Chem. Rev. 1996, 96: 339 -
1d
Giese B.Kopping B.Göbel T.Dickhaut J.Thoma G.Kulicke KJ.Trach F. Org. React. 1996, 48: 301 -
1e
Renaud P.Gerster M. Angew. Chem. Int. Ed. 1998, 37: 2562 -
1f
Sibi MP.Porter NA. Acc. Chem. Res. 1999, 32: 163 -
1g
Bowman WR.Bridge CF.Brookes P. J. Chem. Soc., Perkin Trans. 1 2000, 1 -
1h
Radicals in Organic Synthesis
Vol. 1 and 2:
Renaud P.Sibi MP. Wiley-VCH; Weinheim: 2001. - For reviews see:
-
2a
Hanamoto T.Inanaga J. Tetrahedron Lett. 1991, 32: 3555 -
2b
Russell GA.Yao C.-F.Rajaratnam R.Kim BH. J. Am. Chem. Soc. 1991, 113: 373 -
2c
Russell GA.Wang L.Rajaratnam R. J. Org. Chem. 1996, 61: 8988 -
2d
Bhat B.Swayze EE.Wheeler P.Dimock S.Perbost M.Sanghvi YS. J. Org. Chem. 1996, 61: 8186 -
2e
Bloch R. Chem. Rev. 1998, 98: 1407 -
3a
Risch N.Arend N. Methods of Organic Chemistry, Houben-Weyl, Stereoselective Synthesis E21, Vol. 3:Helmchen G.Hoffmann RW.Mulzer J.Schaumann E. Thieme; Stuttugart: 1996. p.1833-2009 -
3b
Volkmann RA. Comprehensive Organic Synthesis Vol. 1:Trost BM. Pergamon Press; Oxford: 1991. p.355-396 -
3c
Enders D.Reinhold U. Tetrahedron: Asymmetry 1997, 8: 1895 -
3d
Denmark SE.Nicaise OJ.-C. Chem. Commun. 1997, 999 - For reviews and selected examples see:
-
4a
Fallis AG.Brinza IM. Tetrahedron 1997, 53: 17543 -
4b
Naito T. Heterocycles 1999, 50: 505 -
4c
Parker KA.Fokas D. J. Org. Chem. 1994, 59: 3927 -
4d
Della EW.Knill AM. Aust. J. Chem. 1994, 47: 1833 -
4e
Hollingworth GJ.Pattenden G.Schulz DJ. Aust. J. Chem. 1995, 48: 381 -
4f
Chiara JL.Marco-Contelles J.Khiar N.Gallego P.Destabel C.Bernabé M. J. Org. Chem. 1995, 60: 6010 -
4g
Santagostino M.Kilburn JD. Tetrahedron Lett. 1995, 36: 1365 -
4h
Keck GE.Wager TT. J. Org. Chem. 1996, 61: 8366 -
4i
Marco-Contelles J.Gallego P.Rodríguez-Fernández M.Khiar N.Destabel C.Bernabé M.Martínez-Grau A.Chiara JL. J. Org. Chem. 1997, 62: 7397 -
4j
Clive DLJ.Zhang J. Chem. Commun. 1997, 549 -
4k
Iserloh U.Curran DP. J. Org. Chem. 1998, 63: 4711 -
4l
Boiron A.Zillig P.Faber D.Giese B. J. Org. Chem. 1998, 63: 5877 - For reviews see:
-
5a
Friestad GK. Tetrahedron 2001, 57: 5461 -
5b
Miyabe H.Naito T. J. Synth. Org. Chem. Jpn. 2001, 59: 35 -
5c
Miyabe H. Yakugaku Zasshi 2003, 123: 285 - 6
Hart DJ.Seely FL. J. Am. Chem. Soc. 1988, 110: 1631 -
7a
Kim S.Lee IY.Yoon J.-Y.Oh DH. J. Am. Chem. Soc. 1996, 118: 5138 -
7b
Kim S.Yoon J.-Y. J. Am. Chem. Soc. 1997, 119: 5982 -
7c
Kim S.Yoon J.-Y.Lee IY. Synlett 1997, 475 -
7d
Kim S.Cheong JH. Chem. Commun. 1998, 1143 -
7e
Ryu I.Kuriyama H.Minakata S.Komatsu M.Yoon J.-Y.Kim S. J. Am. Chem. Soc. 1999, 121: 12190 -
8a
Miyabe H.Shibata R.Ushiro C.Naito T. Tetrahedron Lett. 1998, 39: 631 -
8b
Miyabe H.Shibata R.Sangawa M.Ushiro C.Naito T. Tetrahedron 1998, 54: 11431 - 9
Miyabe H.Ushiro C.Naito T. Chem. Commun. 1997, 1789 -
10a
Bertrand MP.Feray L.Nouguier R.Stella L. Synlett 1998, 780 -
10b
Bertrand MP.Feray L.Nouguier R.Perfetti P. Synlett 1999, 1148 -
10c
Bertrand MP.Feray L.Nouguier R.Perfetti P. J. Org. Chem. 1999, 64: 9189 -
11a
Friestad GK.Qin J. J. Am. Chem. Soc. 2000, 122: 8329 -
11b
Friestad GK.Qin J. J. Am. Chem. Soc. 2001, 123: 9922 -
11c
Friestad GK.Shen Y.Ruggles EL. Angew. Chem. Int. Ed. 2003, 42: 5061 -
12a For a review see:
Miyabe H.Miyata O.Naito T. J. Synth. Org. Chem. Jpn. 2002, 60: 1087 -
12b
Naito T.Tajiri K.Harimoto T.Ninomiya I.Kiguchi T. Tetrahedron Lett. 1994, 35: 2205 -
12c
Miyabe H.Torieda M.Kiguchi T.Naito T. Synlett 1997, 580 -
12d
Miyabe H.Torieda M.Inoue K.Tajiri K.Kiguchi T.Naito T. J. Org. Chem. 1998, 63: 4397 -
12e
Miyabe H.Kanehira S.Kume K.Kandori H.Naito T. Tetrahedron 1998, 54: 5883 -
12f
Miyata O.Muroya K.Koide J.Naito T. Synlett 1998, 271 -
12g
Naito T.Nakagawa K.Nakamura T.Kasei A.Ninomiya I.Kiguchi T. J. Org. Chem. 1999, 64: 2003 -
12h
Naito T.Fukumoto D.Takebayashi K.Kiguchi T. Heterocycles 1999, 51: 489 -
12i
Kiguchi T.Tajiri K.Ninomiya I.Naito T. Tetrahedron 2000, 56: 5833 -
12j
Miyabe H.Nishiki A.Naito T. Chem. Pharm. Bull. 2003, 51: 100 - 13 For examples employing Lewis acid in radical reactions:
Sibi MP.Ji J. Angew. Chem., Int. Ed. Engl. 1997, 36: 274 ; and references cited therein - 14
Ueda M.Miyabe H.Namba M.Nakabayashi T.Naito T. Tetrahedron Lett. 2002, 43: 4369 - For selected examples see:
-
15a
Hagiwara E.Fujii A.Sodeoka M. J. Am. Chem. Soc. 1998, 120: 2474 -
15b
Ferraris D.Young B.Dudding T.Lectka T. J. Am. Chem. Soc. 1998, 120: 4548 -
15c
Davis FA.McCoull W. J. Org. Chem. 1999, 64: 3396 -
16a
Fiaud J.-C.Kagan HB. Tetrahedron Lett. 1970, 1813 -
16b
Fiaud J.-C.Kagan HB. Tetrahedron Lett. 1971, 1019 -
16c
Yamamoto Y.Ito W. Tetrahedron 1988, 44: 5415 -
16d
Kolasa T.Sharma SK.Miller MJ. Tetrahedron 1988, 44: 5431 -
17a
Hanessian S.Yang R.-Y. Tetrahedron Lett. 1996, 37: 5273 -
17b
Hanessian S.Yang R.-Y. Tetrahedron Lett. 1996, 37: 8997 -
17c
Hanessian S.Lu P.-P.Sancéau J.-Y.Chemla P.Gohda K.Fonne-Pfister R.Prade L.Cowan-Jacob SW. Angew. Chem. Int. Ed. 1999, 38: 3160 -
18a
Hallett DJ.Thomas EJ. J. Chem. Soc., Chem. Commun. 1995, 657 -
18b
Hallett DJ.Thomas EJ. Tetrahedron: Asymmetry 1995, 6: 2575 -
18c
Bradley GW.Hallett DJ.Thomas EJ. Tetrahedron: Asymmetry 1995, 6: 2579 -
19a
Yamamoto Y.Ito W.Maruyama K. J. Chem. Soc., Chem. Commun. 1985, 1131 -
19b
Yamamoto Y.Nishii S.Maruyama K.Komatsu T.Ito W. J. Am. Chem. Soc. 1986, 108: 7778 -
19c
Petasis NA.Zavialov IA. J. Am. Chem. Soc. 1997, 119: 445 -
19d
Petasis NA.Goodman A.Zavialov IA. Tetrahedron 1997, 53: 16463 - 20
Miyabe H.Ushiro C.Ueda M.Yamakawa K.Naito T. J. Org. Chem. 2000, 65: 176 - 21
Miyabe H.Ueda M.Naito T. Chem. Commun. 2000, 2059 -
22a
Miyabe H.Ueda M.Yoshioka N.Naito T. Synlett 1999, 465 -
22b
Miyabe H.Ueda M.Yoshioka N.Yamakawa K.Naito T. Tetrahedron 2000, 56: 2413 -
23a
Kita Y.Sato A.Yamaguchi T.Oka M.Gotanda K.Matsugi M. Tetrahedron Lett. 1997, 38: 3549 -
23b
Kita Y.Gotanda K.Murata K.Suemura M.Sato A.Yamaguchi T.Oka M.Matsugi M. Org. Proc. Res. Dev. 1998, 2: 250 - 24
Miyabe H.Yamakawa K.Yoshioka N.Naito T. Tetrahedron 1999, 55: 11209 - 25
Ryu I.Araki F.Minakata S.Komatsu M. Tetrahedron Lett. 1998, 39: 6335 -
26a
Jezewski A.Chajewska K.Wielogórski Z.Jurczak J. Tetrahedron: Asymmetry 1997, 8: 1741 -
26b
Bauer T. Tetrahedron: Asymmetry 1996, 7: 981 -
26c
Bauer T.Chapuis C.Jezewski A.Kozak J.Jurczak J. Tetrahedron: Asymmetry 1996, 7: 1391 -
27a
Miyabe H.Fujii K.Naito T. Org. Lett. 1999, 1: 569 -
27b
Miyabe H.Fujii K.Naito T. Org. Biomol. Chem. 2003, 1: 381 -
28a
Becker DA. J. Am. Chem. Soc. 1996, 118: 905 -
28b
Park Y.-T.Kim K.-W. J. Org. Chem. 1998, 63: 4494 - Silylnitronates and nitroalkyl anions have been used as radical acceptors:
-
29a
Branchaud BP.Yu G.-X. Tetrahedron Lett. 1991, 32: 3639 -
29b
Kim S.Yoon J.-Y.Lim CJ. Synlett 2000, 1151 - 30
Ueda M.Miyabe H.Teramachi M.Miyata O.Naito T. Chem. Commun. 2003, 426 - 31 For an example of the reaction of nitrones with triethylborane see:
Hollis WG.Smith PL.Hood DK.Cook SM. J. Org. Chem. 1994, 59: 3485 - 32
Garner PP.Parker DT.Gajewski JJ.Lubineau A.Angé J.Queneau Y.Beletskaya IP.Cheprakov AV.Fringuelli F.Piermatti O.Pizzo F.Kobayashi S. Organic Synthesis in WaterGrieco PA. Blackie Academic & Professional; London: 1998. - For reviews see:
-
33a
Li CJ. Chem. Rev. 1993, 93: 2023 -
33b
Lubineau A.Angé J.Queneau Y. Synthesis 1994, 741 -
33c
Li CJ. Tetrahedron 1996, 52: 5643 - Triethylborane-mediated radical reactions in aqueous media see:
-
34a
Yamazaki O.Togo H.Nogami G.Yokoyama M. Bull. Chem. Soc. Jpn. 1997, 71: 2519 -
34b
Yorimitsu H.Nakamura T.Shinokubo H.Oshima K. J. Org. Chem. 1998, 63: 8604 -
34c
Nakamura T.Yorimitsu H.Shinokubo H.Oshima K. Synlett 1998, 1351 -
34d
Kita Y.Nambu H.Ramesh NG.Anikumar G.Matsugi M. Org. Lett. 2001, 3: 1157 -
35a
Posner GH. Chem. Rev. 1986, 86: 831 -
35b
Tempest PA.Brown SD.Armstrong RW. Angew. Chem., Int. Ed. Engl. 1996, 35: 640 - For reviews see:
-
36a
Balkenhohl F.von dem Bussche-Hünnefeld C.Lansky A.Zechel C. Angew. Chem., Int. Ed. Engl. 1996, 35: 2288 -
36b
Thompson LA.Ellman JA. Chem. Rev. 1996, 96: 555 - 36c Acc. Chem. Res. 1996, 29: 112-170 ; all of issue 3
- 36d Chem. Rev. 1997, 97: 347-510 ; all of issue 2
-
36e
Hermkens PHH.Ottenheijm HCJ.Rees DC. Tetrahedron 1997, 53: 5643 -
36f
Brown RCD. J. Chem. Soc., Perkin Trans. 1 1998, 3293 - 37
Miyabe H.Yoshioka N.Ueda M.Naito T. J. Chem. Soc., Perkin Trans. 1 1998, 3659 - 38
Miyabe H.Ueda M.Naito T. J. Org. Chem. 2000, 65: 5043 - For some recent examples see:
-
39a
Backhaus D. Tetrahedron Lett. 2000, 41: 2087 -
39b
Lu W.Chan TH. J. Org. Chem. 2000, 65: 8589 -
39c
Jeevanandam A.Ling YC. Tetrahedron Lett. 2001, 42: 4361 -
39d
Lavilla B.Coll O.Bosch J.Orozco M.Luque FJ. Eur. J. Org. Chem. 2001, 3719 -
39e
Márquez F.Montoro R.Llebaria A.Lago E.Molins E.Delgado A. J. Org. Chem. 2002, 67: 308 -
39f
Yadav JS.Srinivas C. Tetrahedron Lett. 2002, 43: 3837 -
39g
Estevam IHS.Bieber LW. Tetrahedron Lett. 2003, 44: 667 -
40a
Mattes H.Benezra C. Tetrahedron Lett. 1985, 26: 5697 -
40b
Petrier C.Dupuy C.Luche JL. Tetrahedron Lett. 1986, 27: 3149 -
40c
Giese B.Damm W.Roth M.Zehnder M. Synlett 1992, 441 -
40d
Erdmann P.Schäfer J.Springer R.Zeitz H.-G.Giese B. Helv. Chim. Acta 1992, 75: 638 -
40e
Bieber LW.Malvestiti I.Storch EC. J. Org. Chem. 1997, 62: 9061 -
40f
Huang T.Keh CCK.Li CJ. Chem. Commun. 2002, 2440 -
40g
Suàrez RM.Sestelo JP.Sarandeses LA. Synlett 2002, 1435 - 41
Ueda M.Miyabe H.Nishimura A.Sugino H.Naito T. Tetrahedron: Asymmetry 2003, 14: 2857 -
42a
Miyabe H.Ueda M.Nishimura A.Naito T. Org. Lett. 2002, 4: 131 -
42b
Miyabe H.Nishimura A.Ueda M.Naito T. Chem. Commun. 2002, 1454 -
42c
Ueda M.Miyabe H.Nishimura A.Miyata O.Takemoto Y.Naito T. Org. Lett. 2003, 5: 2835 - 43
Routledge A.Abell C.Balasubramanian S. Synlett 1997, 61 -
44a
Du X.Armstrong RW. J. Org. Chem. 1997, 62: 5678 -
44b
Du X.Armstrong RW. Tetrahedron Lett. 1998, 39: 2281 -
45a
Berteina S.De Mesmaeker A. Tetrahedron Lett. 1998, 39: 5759 -
45b
Berteina S.Wendeborn S.De Mesmaeker A. Synlett 1998, 1231 - 46
Watanabe Y.Ishikawa S.Takao G.Tour T. Tetrahedron Lett. 1999, 40: 4535 - 47
Caddick S.Hamza D.Wadman SN. Tetrahedron Lett. 1999, 40: 7285 - 48
Zhu X.Ganesan A. J. Comb. Chem. 1999, 1: 157 - 49
Enholm EJ.Gallagher ME.Jiang S.Batson WA. Org. Lett. 2002, 2: 1443 - 50
Sibi MP.Chandramouli SV. Tetrahedron Lett. 1997, 38: 8929 - For reviews see:
-
51a
Miyabe H. Yakugaku Zasshi 2000, 120: 667 -
51b
Naito T.Miyabe H. J. Synth. Org. Chem. Jpn. 2002, 60: 484 -
52a
Miyabe H.Fujishima Y.Naito T. J. Org. Chem. 1999, 64: 2174 -
52b
Miyabe H.Nishimura A.Fujishima Y.Naito T. Tetrahedron 2003, 59: 1901 - Unpublished results. For the discussions see:
-
54a
Fitch WL.Detre G.Holmes CP.Shoolery JN.Keifer PA. J. Org. Chem. 1994, 59: 7955 -
54b
Keifer PA. J. Org. Chem. 1996, 61: 1558 -
55a
Miyabe H.Konishi C.Naito T. Org. Lett. 2000, 2: 1443 -
55b
Miyabe H.Konishi C.Naito T. Chem. Pharm. Bull. 2003, 51: 540 - 56
Miyabe H.Tanaka H.Naito T. Tetrahedron Lett. 1999, 40: 8387 - 57
Miyabe H.Fujii K.Tanaka H.Naito T. Chem. Commun. 2001, 831 - 58 For study on the intramolecular reactions of alkoxycarbonyl-stabilized radicals with electron rich alkene acceptor see:
Russell GA.Li C. Tetrahedron Lett. 1996, 37: 2557 -
59a
Miyabe H.Fujii K.Goto T.Naito T. Org. Lett. 2000, 2: 4071 -
59b
Miyabe H.Ueda M.Fujii K.Nishimura A.Naito T. J. Org. Chem. 2003, 68: 5618 - The reaction between Et3B and the radical in α-position to an ester is less effective than the corresponding reaction of the radical deriving from ketones and aldehydes. For the discussions see:
-
60a
Ollivier C.Renaud P. Angew. Chem. Int. Ed. 2000, 39: 925 -
60b
Brown HC.Negishi E. J. Am. Chem. Soc. 1971, 93: 3777 -
60c
Beraud V.Gnanou Y.Walton JC.Maillard B. Tetrahedron Lett. 2000, 41: 1195
References
Wang and TentaGel OH resins purchased from Novabiochem were used in all experiments.