Subscribe to RSS
DOI: 10.1055/s-0029-1218351
Ring Expansion of 2-Alkenyl Azetidines into Unsaturated Azocanes
Publication History
Publication Date:
11 November 2009 (online)
Abstract
Enantiomerically pure 2-alkenyl azetidines undergo a ring expansion into N-alkyl-1,2,3,6-azocines upon reaction with activated alkynes (ethyl propiolate or ethynyl p-tolyl sulfone). The scope of this ring enlargement, which provides a new entry to functionalized eight-membered ring nitrogen heterocycle, is discussed.
Key words
azetidines - ring expansion - azocanes
- For general reviews on the synthesis of azetidines prior to 2000, see:
-
1a
Moore JA. In Heterocyclic Compounds with Three and Four-Membered RingsWeissberger A. Interscience Publishers; New-York: 1964. Part 2. p.885-977 -
1b
Cromwell NH.Phillips B. Chem. Rev. 1979, 79: 331 -
1c
Moore JA.Ayers RS. In Small Ring Heterocycles-Part 2-Azetidines, β-Lactams, Diazetidines, and DiaziridinesHassner A. John Wiley and Sons, Inc.; New York: 1983. p.1 -
1d
De Kimpe N. Azetidines, Azetines and Azete, In Comprehensive Heterocyclic Chemistry II, a review of the Literature of 1982-1995 Vol. 1B: Pergamon; Oxford: 1996. - For more recent reviews, see:
-
1e
Dejaegher Y.Kuz’menok NM.Zvonok AM.De Kimpe N. Chem. Rev. 2002, 102: 29 -
1f
Couty F.Evano G.Prim D. Mini-Rev. Org. Chem. 2004, 1: 133 -
1g
Couty F.Evano G. Org. Prep. Proced. Int. 2006, 38: 427 -
1h
Brandi A.Cicchi S.Cordero FM. Chem. Rev. 2008, 108: 3988 -
1i
Couty F. Synthesis of Azetidines, In Science of Synthesis: Houben-Weyl Methods of Molecular Transformations Vol. 40a:Enders D. Georg Thieme Verlag; New York: 2009. p.773-817 - 2
Padwa A.Gruber R. J. Am. Chem. Soc. 1970, 92: 107 - 3
Roberto D.Alper H. J. Am. Chem. Soc. 1989, 111: 7539 -
4a
Durrat F.Vargas-Sanchez M.Couty F.Evano G.Marrot J. Eur. J. Org. Chem. 2008, 3286 -
4b
Drouillat B.Couty F.David O.Evano G.Marrot J. Synlett 2008, 1345 -
4c
Van Bradandt W.Van Landeghem R.De Kimpe N. Org. Lett. 2006, 8: 1105 - 5
Ungureanu I.Klotz P.Schoenfelder A.Mann A. Chem. Commun. 2001, 958 - 6
Couty F.Durrat F.Evano G.Marrot J. Eur. J. Org. Chem. 2006, 4214 - 7 For a review on this topic, see:
Couty F.Durrat F.Evano G. Targets in Heterocyclic Systems-Chemistry and Properties Vol. 9:Attanasi OA.Spinelli D. Italian Society of Chemistry; Rome: 2005. p.186 - 8
Weston MH.Nakajima K.Parvez M.Back TG. Chem. Commun. 2006, 3903 - 9
Weston MH.Nakajima K.Back TG. J. Org. Chem. 2008, 73: 4630 - 10
Winnick MA. Chem. Rev. 1981, 81: 491 - For examples of macrocyclisation involving N-alkylation, see
-
11a
Kan T.Fujiwara A.Kobayashi H.Fukuyama T. Tetrahedron 2002, 58: 6267 -
11b
Dolman SJ.Sattely ES.Hoveyda AH.Schrock RR. J. Am. Chem. Soc. 2002, 124: 6991 -
11c
Sattely ES.Cortez GA.Moebius DC.Schrock RR.Hoveyda AH. J. Am. Chem. Soc. 2005, 127: 8526 - For examples of RCM, see:
-
11d
Gille S.Ferry A.Billard T.Langlois BR. J. Org. Chem. 2003, 68: 8932 - For examples of ring cleavage, see:
-
11e
Vedejs E.Galante RJ.Goekjian PG. J. Am. Chem. Soc. 1998, 120: 3613 -
11f
Iradier F.Arrayás RG.Carretero C. Org. Lett. 2001, 3: 2957 -
11g For examples of rearrangement,
see:
MaGee DI.Beck EJ. J. Org. Chem. 2000, 65: 8367 - For examples of [2,3]-sigmatropic shifts, see:
-
11h
Vedejs E.Hagen JP.Roach BL.Spear KL. J. Org. Chem. 1978, 43: 1185 -
11i
Voskressensky LG.Listratova AV.Borisova TN.Kovaleva SA.Borisov RS.Varlamov AV. Tetrahedron 2008, 64: 10443 - 12
White JD. J. Org. Chem. 2000, 65: 9129 ; See also ref. 11e -
13a
Godin G.Garnier E.Compain P.Martin OR.Ikeda K.Asano N. Tetrahedron Lett. 2004, 45: 579 -
13b
Chang M.-Y.Kung Y.-H.Ma C.-C.Chen S.-T. Tetrahedron 2007, 63: 1339 - 14
Couty F.Prim D. Tetrahedron: Asymmetry 2006, 13: 2619 - 15
Walters MA. J. Org. Chem. 1996, 61: 978 - 16
Ramachandran PV.Rudd MT.Reddy MR. Tetrahedron Lett. 2005, 46: 2547
References and Notes
Typical Procedure
for the Ring Expansion of 2-Alkenyl Azetidines into Unsaturated
Azocanes: The following procedure for the preparation of azocane 8 is representative. To a solution of azetidine 9 (800 mg, 3.03 mmol) in absolute EtOH
(30 mL), was added in one portion, ethyl propiolate (0.62 mL, 6.06
mmol). The reaction mixture was stirred for 5 days and concentrated
under reduced pressure. The crude residue was purified by flash
chromatography (Pentane-Et2O, 75:25 + 0.1% Et3N)
to afford 8 as a colourless oil (911 mg,
82%).
Compound 8: R
f
= 0.30
(Pentane-Et2O, 75:25); [α]D
²5 -957 (c 0.95, CH2Cl2); ¹H
NMR (300 MHz): δ = 0.95 (d, J = 6.7 Hz,
3 H, Me), 1.17 (t, J = 7.1
Hz, 3 H, OCH2CH
3),
2.95 (dd, J = 12.0,
6.5 Hz, 1 H, H7), 3.41-3.60 (m, 2 H,
H4), 4.08 (q, J = 7.1
Hz, 2 H, OCH
2), 4.27
(d, J = 15.8
Hz, 1 H, NCHH), 4.43 (d, J = 15.8 Hz,
1 H, NCHH), 4.64 (m, 1 H,
H8), 5.39 (dd, J = 11.1,
6.5 Hz, 1 H, H6), 5.56 (m, 1 H, H5), 7.03 (d, J = 7.9 Hz,
1 H, Ar), 7.11-7.27 (m, 9 H, Ar), 7.57
(s, 1 H, H2); ¹³C NMR (75
MHz): δ = 14.6 (CH3CH2),
18.7 (CH3), 25.1 (C4), 53.3 (NCH2), 56.0,
57.6 (C7, C8), 59.7 (OCH2), 94.9 (C3), 125.2, 126.8,
127.5, 128.4, 128.5, 128.6, 132.0 (C5, C6, CHAr), 139.1, 141.2 (CqAr),
151.9 (C2), 170.0 (C=O); MS (ESI): m/z (%) = 385.3 (20) [M + Na+],
362.2 (100) [M + H+].
Compound 7: white solid; mp 74 ˚C; R
f
= 0.25
(Pentane-Et2O, 75:25); [α]D
²5 -548
(c 3.3, CH2Cl2); ¹H
NMR (300 MHz): δ = 1.07 (d, J = 6.5
Hz, 3 H, Me), 2.47 (s, 3 H, Me), 3.02-3.16
(m, 2 H, H4, H7), 3.74 (dd, J = 16.2,
7.5 Hz, 1 H, H4′), 4.44 (d, J = 15.8
Hz, 1 H, NCHH), 4.58 (d, J = 15.8 Hz,
1 H, NCHH), 4.64 (m, 1 H, H8),
5.24 (m, 1 H, H5), 5.50 (m, 1 H, H6), 7.03 (m,
2 H, Ar), 7.19-7.44 (m, 10 H, Ar), 7.64
(s, 1 H, H2), 7.72 (d, J = 6.7 Hz,
2 H, Ar); ¹³C NMR (75 MHz): δ = 18.7
(CH3), 21.5 (CH3), 25.4 (C4), 53.2 (NCH2),
56.3, 57.7 (C7, C8), 102.5 (C3), 123.2, 125.5, 127.0, 127.2, 127.3,
127.6, 127.8, 128.3, 128.5, 128.7, 128.8, 129.4, 133.0 (C2, C5,
C6, CHAr), 138.8, 139.9, 140.6, 142.4 (CqAr), 149.9 (C2); MS (ESI):
m/z (%) = 466.3
(100) [M + Na+].