Subscribe to RSS
DOI: 10.1055/s-0030-1259320
Chiral Amine-Triggered Triple Cascade Reactions: A New Approach to Functionalized Decahydroquinolines
Publication History
Publication Date:
13 January 2011 (online)
![](https://www.thieme-connect.de/media/synlett/201103/lookinside/thumbnails/10.1055-s-0030-1259320-1.jpg)
Abstract
A chiral amine-triggered highly enantio- and diastereoselective synthesis yielding 69-94% of cis-decahydroquinolines is reported. The synthetic protocol involves a [2+2+2]-annulation via (S)-diphenylprolinol trimethylsilyl ether catalyzed Michael addition of cyclohexanone to nitroalkenes followed by aza-Henry-hemiaminalization reaction cascade. The process stereoselectively installs five contiguous chiral centers into the quinoline structure.
Key words
organocatalysis - quinolines - nitroalkenes - cascade reactions - stereoselective synthesis
- 1
Guo H.-C.Ma J.-A. Angew Chem. Int. Ed. 2006, 45: 354 - 2
Nicolaou KC.Montagnon T.Snyder SA. Chem. Commun. 2003, 551 -
3a
Dalko PI.Moisan L. Angew Chem. Int. Ed. 2001, 40: 3726 -
3b
List B. Synlett 2001, 1675 -
3c
List B. Tetrahedron 2002, 58: 2481 -
3d
Dalko PI.Moisan L. Angew Chem. Int. Ed. 2004, 43: 5138 -
3e
Berkessel A.Gröger H. Asymmetric Organocatalysis Wiley-VCH; Weinheim: 2005. -
3f
Seayad J.List B. Org. Biomol. Chem. 2005, 3: 719 -
3g
Lelais G.Macmillan WC. Aldrichimica Acta 2006, 39: 79 -
4a
List B. Chem. Commun. 2006, 819 -
4b
Yua X.Wang W. Org. Biomol. Chem. 2008, 6: 2037 -
4c
Melchiorre P.Marigo M.Carlone A.Bartoli G. Angew. Chem. Int. Ed. 2008, 47: 6138 -
4d
Spande TF.Jain P.Garraffo HM.Pannell LK.Yeh HJC.Daly JW.Fukumoto S.Imamura K.Tokuyama T.Torres JA.Snelling RR.Jones TH. J. Nat. Prod. 1999, 62: 5 -
4e
Jones TH.Gorman JST.Snelling RR.Delabie JHC.Blum MS.Garraffo HM.Jain P.Daly JW.Spande TF. J. Chem. Ecol. 1999, 25: 1179 -
4f
Daly JW.Garraffo HM.Jain P.Spande TF.Snelling RR.Jaramillo C.Rand AS. J. Chem. Ecol. 2000, 26: 73 -
4g
Daly JW.Spande TF.Garraffo HM. J. Nat. Prod. 2005, 68: 1556 -
5a
Enders D.Hüttl MRM.Grondal C.Raabe G. Nature (London) 2006, 44: 861 -
5b
Enders D.Jeanty M.Bats JW. Synlett 2009, 3175 -
5c
Grondal C.Jeanty M.Enders D. Nature Chem. 2010, 2: 167 -
5d
Enders D.Grondal C.Hüttl MRM. Angew. Chem. Int. Ed. 2007, 46: 1570 -
5e
Wang Y.Han R.-G.Zhao Y.-L.Yang S.Xu P.-F.Dixon DJ. Angew. Chem. Int. Ed. 2009, 48: 1 -
5f
Eder U.Saver G.Wiechert R. Angew. Chem., Int. Ed. Engl. 1971, 10: 496 -
5g
Hajor ZG.Parrish DR. J. Org. Chem. 1974, 39: 1615 -
5h
Halland N.Aburel PS.Jørgensen KA. Angew. Chem. Int. Ed. 2004, 43: 1272 -
5i
Hong B.-C.Wu M.-F.Tseng H.-C.Liao J.-H. Org. Lett. 2006, 8: 2271 -
6a
Chandrasekhar S.Mallikarjun K.Pavankumarreddy G.Rao KV.Jagadeesh B. Chem. Commun. 2009, 4985 -
6b
Wang Y.Yu D.-F.Liu Y.-Z.Wei H.Luo Y.-C.Dixon DJ.Xu P.-F. Chem. Eur. J. 2010, 16: 3922 -
6c
Urushima T.Sakamoto D.Ishikawa H.Hayashi Y. Org. Lett. 2010, 12: 4588 - 7
Ko S.Yao C.-F. Tetrahedron 2006, 62: 7293 -
8a
Steffan B. Tetrahedron 1991, 47: 8729 -
8b
Kubanek J.Williams DE.Dilip de Silva E.Allen T.Andersen RJ. Tetrahedron Lett. 1995, 36: 6189 -
8c
Davis RA.Carroll AR.Quinn RJ. J. Nat. Prod. 2002, 65: 454 -
9a
Warnick JE.Jessup PJ.Overman LE.Eldefrawi ME.Nimit Y.Daly JW.Albuquerque EX. Mol. Pharmacol. 1982, 22: 565 -
9b
Daly JW.Nishizawa Y.Padgett WL.Tokuyama T.McCloskey PJ.Waykole L.Schultz AG.Aronstam RS. Neurochem. Res. 1991, 16: 1207 - 10
Daly JW.Tokuyama T.Habermehl G.Karle IL.Witkop B. Liebigs Ann. Chem. 1969, 727: 198 - 11
Sainani JB.Shah AC. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 1994, 33: 526 - 12
Tokuyama T.Tsujita T.Shimada A.Garraffo HM.Spande TF.Daly JW. Tetrahedron 1991, 47: 5401 - 13
Daly JW.Witkop B.Tokuyama T.Nishikawa T.Karle IL. Helv. Chim. Acta 1977, 60: 1128 -
14a
Oppolzer W.Fröstl W.Weber HP. Helv. Chim. Acta 1975, 58: 593 -
14b
Girard N.Hurvois J.-P.Moinet C.Toupet L. Eur. J. Org. Chem. 2005, 2269 - 15
Efange SMN.Khare AB.Mach RH.Parsons SM. J. Med. Chem. 1999, 42: 2862 - 16
Li M.Zuo Z.Wen L.Wang S. J. Comb. Chem. 2008, 10: 436 - 17
Tu SJ.Zhou JF.Deng X.Cai PJ.Wang H.Feng JC. Chin. J. Org. Chem. 2001, 21: 313 - 18
Sabitha G.Reddy GSK.Reddy CS.Yadav JS. Tetrahedron Lett. 2003, 44: 4129 - 19
Ji SJ.Jiang ZQ.Lu J.Loa TP. Synlett 2004, 831 - 20
Zhang XY.Li YZ.Fan XS.Qu GR.Hu XY.Wang JJ. Chin. Chem. Lett. 2006, 17: 150 - 21
Maheswara M.Siddaiah V.Damu GLV.Venkata Rao C. ARKIVOC 2006, (ii): 201 - 22
Das B.Ravikanth B.Ramu R.Vittal Rao B. Chem. Pharm. Bull. 2006, 54: 1044 - 23
Song G.Wang B.Wu X.Kang Y.Yang L. Synth. Commun. 2005, 35: 2875 - 24
Reddy CS.Raghu M. Chin. Chem. Lett. 2008, 19: 775 - 25
Adibi H.Samimi HA.Beygzadeh M. Catal. Commun. 2007, 8: 2119 - 26
Heravi MM.Bakhtiri K.Javadi NM.Bamoharram FF.Saeedi M.Oskooi HA. J. Mol. Catal. A: Chem. 2007, 264: 50 - 27
Donelson JL.Gibbs A.De S K. J. Mol. Catal. A: Chem. 2006, 256: 309 - 28
Cherkupally SR.Mekalan R. Chem. Pharm. Bull. 2008, 56: 1002 - 29
Sapkal SB.Shelke KF.Shingate BB.Shingare MS. Tetrahedron Lett. 2009, 50: 1754 - 30
Kibayashi C.Aoyagi S. Stud. Nat. Prod. Chem. 1997, 9: 3 -
31a
Ballini R.Rosini G. Synthesis 1988, 833 -
31b
Rosini G.Ballini R.Petrini M.Marotta E.Righi P. Org. Prep. Proced. Int. 1990, 22: 707 -
31c
Ballini R.Marziali P.Mozzicafreddo A. J. Org. Chem. 1996, 61: 3209 -
31d
Ballini R.Bosica G. Tetrahedron Lett. 1996, 37: 8027 -
31e
Ballini R.Bosica G. J. Org. Chem. 1997, 62: 425 -
31f
Ballini R.Petrini M. Tetrahedron 2004, 60: 1017 -
31g
Amantini D.Fringuelli F.Piermatti O.Pizzo F.Vaccaro C. J. Org. Chem. 2003, 68: 9263 -
31h
Marotta E.Righi P.Rosini G. Tetrahedron Lett. 1998, 39: 1041 -
31i
Areces P.Gil MV.Higes FJ.Romàn E.Serrano JA. Tetrahedron Lett. 1998, 39: 8557 - 32
Pinnick HW. Org. React. (N.Y.) 1990, 38: 655 -
33a
Yadav LDS.Rai A. Synlett 2009, 1067 -
33b
Yadav LDS.Rai A. Tetrahedron Lett. 2009, 50: 640 -
33c
Yadav LDS.Rai A. Tetrahedron Lett. 2008, 49: 5751 -
33d
Awasthi C.Yadav LDS. Synlett 2010, 1783 -
34a
Yadav LDS.Rai A.Rai VK.Awasthi C. Tetrahedron 2008, 64: 1420 -
34b
Yadav LDS.Rai VK.Singh S.Singh P. Tetrahedron Lett. 2010, 51: 1657 -
34c
Yadav LDS.Singh S.Rai VK. Synlett 2010, 240 -
34d
Singh S.Rai VK.Singh P.Yadav LDS. Synthesis 2010, 2957
References and Notes
General Procedure
for the Synthesis of
cis
-Decahydro-quinolines 5: To a solution
of ketone 1 (0.4 mmol) and the catalyst
diphenylprolinol trimethylsilyl ether 4a (20
mol%) in 1,4-dioxane (1 mL) was added nitroalkene 2 (0.4 mmol) under stirring. The reaction
mixture was stirred at r.t. for 8 h followed by addition of aldimine 3 (0.4 mmol) along with K2CO3 (0.2
mmol) in 1,4-dioxane (2 mL) and stirring at r.t. until complete
consumption of aldimine 3 (11-18
h) as indicated by TLC. The reaction mixture was concentrated under
reduced pressure and the residue was directly purified by silica
gel column chromatography (EtOAc-hexane as eluent) to afford
an analytically pure sample of cis-decahydroquinolines 5 (Table
[²]
).
Characterization Data of Representative Compounds
cis
-5:
Compound cis-
5a:
white solid; yield: 78%; mp 178-179 ˚C. IR
(KBr): 3589, 2964, 1554, 1534, 1408, 1348, 1174, 1092, 856, 797,
745, 702, 605 cm-¹. ¹H
NMR (400 MHz, DMSO-d
6): δ = 1.10-1.33
(m, 4 H), 1.60-1.76 (m, 5 H), 1.92 (br s, 1 H, exch. D2O),
2.34 (s, 3 H), 3.34 (dd, 1 H, J = 11.7,
11.6 Hz), 5.06 (d, 1 H, J = 11.1
Hz), 5.91 (dd, 1 H, J = 11.7,
11.1 Hz), 7.34 (d, 2 H, J = 8.1
Hz), 7.45-7.75 (m, 10 H), 7.72 (d, 2 H, J = 8.5
Hz). ¹³C NMR (100 MHz, DMSO-d
6): δ = 17.1, 18.7,
23.6, 24.3, 25.1, 30.4, 37.9, 42.7, 75.1, 84.8, 124.8, 126.0, 127.4,
128.1, 129.3, 130.6, 131.7, 134.6, 137.9, 140.1, 141.5, 142.7. EIMS: m/z = 506 [M+].
Anal. Calcd for C28H30N2O5S:
C, 66.38; H, 5.97; N, 5.53. Found: C, 66.10; H, 5.61; N, 5.83. [α]D
²0 +22
(c = 0.60, THF). The enantiomeric
excess was determined to be 97% by HPLC on a chiral Eurocel
column (250 × 4.6 mm, 5 µm): λ = 225
nm; i-PrOH-hexane (10:90), flow
rate: 1 mL/min; t
R
= 5.8 min (minor), t
R
= 6.8
min (major).
Compound cis-
5e: white solid; yield: 90%; mp
189-190 ˚C. IR (KBr): 3598, 2952, 1557, 1532,
1402, 1345, 1161, 1090, 854, 799, 741, 710, 606 cm-¹. ¹H
NMR (400 MHz, DMSO-d
6): δ = 1.06-1.30
(m, 4 H), 1.61-1.79 (m, 5 H), 1.94 (br s, 1 H, exch. D2O),
2.36 (s, 3 H), 3.35 (dd, 1 H, J = 11.8,
11.6 Hz), 5.05 (d, 1 H, J = 11.2
Hz), 5.93 (dd, 1 H, J = 11.8,
11.2 Hz), 7.30 (d, 2 H, J = 8.1
Hz), 7.65-7.70 (m, 2 H), 7.66-7.71 (m, 5 H), 7.72
(d, 2 H, J = 8.3 Hz), 8.10-8.17
(m, 2 H).
¹³C NMR (100 MHz,
DMSO-d
6): δ = 18.9,
20.1, 21.8, 22.7, 25.2, 27.6, 34.9, 39.3, 75.4, 84.5, 125.1, 126.9,
127.8, 128.6, 129.5, 131.1, 132.9, 134.4, 137.0, 138.3, 140.4, 141.6. EIMS: m/z = 540 [M+].
Anal. Calcd for C28H29ClN2O5S:
C, 62.16; H, 5.40; N, 5.18. Found: C, 62.52; H, 5.58; N, 4.86. [α]D
²0 +19
(c = 0.80, THF). The enantiomeric
excess was determined to be 91% by HPLC on a chiral Eurocel
column (250 × 4.6 mm, 5 µm): λ = 225
nm; i-PrOH-hexane (10:90), flow
rate: 1 mL/min; t
R
= 5.9 min (minor), t
R
= 7.1
min (major).
Compound cis-
5m: white solid; yield: 71%; mp
187-188 ˚C. IR (KBr): 3592, 2815, 2910, 1559,
1531, 1410, 1340, 1169, 1095, 852, 796, 741, 708, 601 cm-¹. ¹H
NMR (400 MHz, DMSO-d
6): δ = 1.09-1.34
(m, 4 H), 1.59-1.76 (m, 5 H), 1.91 (br s, 1 H, exchangeable
with D2O), 2.33 (s, 3 H), 3.34 (dd, 1 H, J = 11.6, 11.4 Hz), 3.85 (s,
3 H), 5.09 (d, 1 H, J = 11.2 Hz),
5.95 (dd, 1 H, J = 11.6, 11.2
Hz), 7.31 (d, 2 H, J = 8.0 Hz),
7.61-7.69 (m, 5 H), 7.66-7.68 (m, 2 H), 7.74 (d,
2 H,
J = 8.2 Hz),
8.01-8.03 (m, 2 H). ¹³C NMR
(100 MHz, DMSO-d
6): δ = 17.6,
18.8, 21.5, 24.3, 25.6, 28.9, 37.5, 42.1, 49.5, 75.4, 84.2, 114.8,
126.7, 127.9, 128.8, 130.0, 131.7, 132.5, 134.7, 136.7, 138.1, 141.6,
156.6. EIMS: m/z = 536 [M+].
Anal. Calcd for C29H32N2O6S:
C, 64.91; H, 6.01; N, 5.22. Found: C, 65.11; H, 5.77; N, 4.93. [α]D
²0 +25
(c = 0.90, THF). The enantiomeric
excess was determined to be 94% by HPLC on a chiral Eurocel
column (250 × 4.6 mm, 5 µm): λ = 225
nm; i-PrOH-hexane (10:90), flow
rate: 1 mL/min; t
R
= 6.7 min (minor), t
R
= 7.8
min (major).