Abstract
Asymmetric conjugate addition of bromonitromethane to α,β-unsaturated
ketones was studied using a series of chiral primary amines as the
catalysts. The cascade intramolecular cyclopropanation provided
nitrocyclopropanes efficiently. Excellent enantioselctivities and
good yields were obtained for several cyclic enones catalyzed by
a bifunctional thiourea-primary amine. Both acid and base
additives were found to be necessary for the transformation.
Key words
asymmetric conjugate addition - bromonitromethane - α,β-unsaturated ketone - nitrocyclopropane
- organocatalysis
References and Notes
For the reviews of cyclopropanes
as the structure motif in drugs and natural products, see:
<A NAME="RW14509ST-1A">1a </A>
Donaldson WA.
Tetrahedron
2001,
57:
8589
<A NAME="RW14509ST-1B">1b </A>
Faust R.
Angew.
Chem. Int. Ed.
2001,
40:
2251
<A NAME="RW14509ST-1C">1c </A>
Wessjohann LA.
Brandt W.
Thiemann T.
Chem. Rev.
2003,
103:
1625
For the reviews of cyclopropanes
as useful synthetic intermediates, see:
<A NAME="RW14509ST-2A">2a </A>
Wong HNC.
Hon MY.
Tse
CW.
Yip YC.
Tanitroalkeneo J.
Hudlicky T.
Chem. Rev.
1989,
89:
165
<A NAME="RW14509ST-2B">2b </A>
Reissig HU.
Zimmer R.
Chem. Rev.
2003,
103:
1151
For the reviews of asymmetric synthesis
of cyclopropanes, see:
<A NAME="RW14509ST-3A">3a </A>
Pellissier H.
Tetrahedron
2008,
64:
7041
<A NAME="RW14509ST-3B">3b </A>
Lebel H.
Marcoux JF.
Molinaro C.
Charette AB.
Chem. Rev.
2003,
103:
977
For the general reviews of asymmetric
organocatalysis, see:
<A NAME="RW14509ST-4A">4a </A>
Dondoni A.
Massi A.
Angew. Chem. Int. Ed.
2008,
47:
4638
<A NAME="RW14509ST-4B">4b </A>
Yu XH.
Wang W.
Chem. Asian J.
2008,
3:
516
<A NAME="RW14509ST-4C">4c </A>
MacMillan DWC.
Nature (London)
2008,
455:
304
<A NAME="RW14509ST-4D">4d </A>
Dalko PI.
Enantioselective Organocatalysis
Wiley-VCH;
Weinheim:
2007.
For recent reviews of organocatalytic
asymmetric conjugate addition, see:
<A NAME="RW14509ST-5A">5a </A>
Almasi D.
Alonso DA.
Najera C.
Tetrahedron:
Asymmetry
2007,
18:
299
<A NAME="RW14509ST-5B">5b </A>
Tsogoeva SB.
Eur. J. Org. Chem.
2007,
11:
1701
<A NAME="RW14509ST-6A">6a </A>
Zlatopolskiy BD.
Loscha K.
Alvermann P.
Kozhushkov SI.
Nikolaev SV.
Zeeck A.
de Meijere A.
Chem. Eur. J.
2004,
10:
4708
<A NAME="RW14509ST-6B">6b </A>
Zindel J.
de Meijere A.
J. Org. Chem.
1995,
60:
2968
<A NAME="RW14509ST-6C">6c </A>
Andres N.
Wolf H.
Zaehner H.
Roessner E.
Zeeck A.
Koenig WA.
Sinnwell V.
Helv. Chim.
Acta
1989,
72:
426
<A NAME="RW14509ST-7A">7a </A>
Gootz TD.
Brighty KE.
Med. Res. Rev.
1996,
16:
433
<A NAME="RW14509ST-7B">7b </A>
Brighty KE.
Castaldi MJ.
Synlett
1996,
1097
<A NAME="RW14509ST-8">8 </A>
Xuan YN.
Nie SZ.
Dong LT.
Zhang JM.
Yan M.
Org.
Lett.
2009,
11:
1583
<A NAME="RW14509ST-9">9 </A>
Inokuma T.
Sakamoto S.
Takemoto Y.
Synlett
2009,
1627
<A NAME="RW14509ST-10A">10a </A>
Zhang JM.
Hu ZP.
Dong LT.
Xuan YN.
Yan M.
Tetrahedron: Asymmetry
2009,
20:
355
<A NAME="RW14509ST-10B">10b </A>
Vesely J.
Zhao GL.
Bartoszewicz A.
Cordova A.
Tetrahedron Lett.
2008,
49:
4209
<A NAME="RW14509ST-11A">11a </A>
Hansen HM.
Longbottom DA.
Ley SV.
Chem. Commun.
2006,
4838
<A NAME="RW14509ST-11B">11b </A>
Wascholowski V.
Hansen
HM.
Longbottom DA.
Ley SV.
Synthesis
2008,
1269
<A NAME="RW14509ST-12">12 </A>
Lv J.
Zhang JM.
Lin Z.
Wang YM.
Chem. Eur. J.
2009,
15:
972
<A NAME="RW14509ST-13">13 </A>
Dong LT.
Lu RJ.
Du QS.
Zhang JM.
Liu SP.
Xuan YN.
Yan M.
Tetrahedron
2009,
65:
4124
For the reviews of bifunctional
organocatalysts, see:
<A NAME="RW14509ST-14A">14a </A>
Connon SJ.
Chem. Eur. J.
2006,
12:
5418
<A NAME="RW14509ST-14B">14b </A>
Taylor MS.
Jacobsen EN.
Angew.
Chem. Int. Ed.
2006,
45:
1520
<A NAME="RW14509ST-15A">15a </A>
Tsogoeva SB.
Wei SW.
Chem. Commun.
2006,
1451
<A NAME="RW14509ST-15B">15b </A>
Huang HB.
Jacobsen EN.
J.
Am. Chem. Soc.
2006,
128:
7170
<A NAME="RW14509ST-15C">15c </A>
Lalonde MP.
Chen YG.
Jacobsen EN.
Angew. Chem. Int. Ed.
2006,
45:
6366
<A NAME="RW14509ST-15D">15d </A>
Yalalov DA.
Tsogoeva SB.
Schmatz S.
Adv. Synth. Catal.
2006,
348:
826
<A NAME="RW14509ST-15E">15e </A>
Wei SW.
Yalalov DA.
Tsogoeva SB.
Schmatz S.
Catal.
Today
2007,
121:
151
<A NAME="RW14509ST-15F">15f </A>
Liu K.
Cui HF.
Nie J.
Dong KY.
Li XJ.
Ma JA.
Org. Lett.
2007,
9:
923
<A NAME="RW14509ST-15G">15g </A>
Zhang XJ.
Liu SP.
Lao JH.
Du
GJ.
Yan M.
Chan ASC.
Tetrahedron:
Asymmetry
2009,
20:
1451
<A NAME="RW14509ST-16A">16a </A>
Li PF.
Wen SG.
Yu F.
Liu QX.
Li WJ.
Wang YC.
Liang XM.
Ye JX.
Org.
Lett.
2009,
11:
753
<A NAME="RW14509ST-16B">16b </A>
Mei K.
Jin M.
Zhang SL.
Li P.
Liu WJ.
Chen XB.
Xue F.
Duan WH.
Wang W.
Org.
Lett.
2009,
11:
2864
<A NAME="RW14509ST-16C">16c </A>
Li PF.
Wang YC.
Liang XM.
Ye JX.
Chem. Commun.
2008,
3302
<A NAME="RW14509ST-17">17 </A>
Typical Procedure
for the Conjugate Addition of Bromonitromethane to α,β-Unsaturated
Ketones
Catalyst 1e (24 mg,
0.05 mmol), PhCOOH (6 mg, 0.05 mmol), and cyclohex-2-one (2a , 29 mg, 0.3 mmol) was dissolved in THF
(0.5 mL). The solution was stirred at r.t. for 15 min. Then NMM
(23 mg, 0.25 mmol) and bromonitro-methane (3 ,
35 mg, 0.25 mmol) was added, and the reaction mixture was stirred
at r.t. for 24 h. The reaction solution was diluted with CH2 Cl2 (5
mL) and washed with aq sat. NaHCO3 (3 mL). The organic
layer was dried over anhyd Na2 SO4 . After the
solvent was evaporated under vacuum, the residue was purified by
flash column chromatography over silica gel (EtOAc-PE)
to provide nitrocyclopropane 4a as a white
solid.