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Rahman Shah Zaib Saleem
Michigan State Universityg y
October 24, 2007
Outline• INTRODUCTION• REACTION INSIGHT
Outline
• VARIANTS OF POVAROV REACTION• SINGLE ELECTRON MECHANISM• ASYMMETRIC CATALYSIS• CONCLUSIONS• CONCLUSIONS
Outline• INTRODUCTION
– HISTORYPOTENTIAL APPLICATIONS
Outline
– POTENTIAL APPLICATIONS• REACTION INSIGHT• VARIANTS OF POVAROV REACTION• SINGLE ELECTRON MECHANISMSINGLE ELECTRON MECHANISM• ASYMMETRIC CATALYSIS• CONCLUSIONS
Introduction: DiscoveryIntroduction: Discovery1962
Povarov and Mikhailov
Potential of generating 3 chiral centers in a single step
BF3.OEt2 pTsOH
R1=OR, SR
Considered as inverse electron demand aza-Diels Alder reactionConsidered as inverse electron demand aza-Diels Alder reaction
Reaction is also cited in the literature by the names:- Imino-Diels Alder reaction
A a Diels Alder reaction
Povarov, L. S. Russ. Chem. Rev. 1967, 36, 656-670.
- Aza-Diels Alder reaction
Introduction: Reaction revisitedIntroduction: Reaction revisited
TFA
MeCN, r.t.
Grieco, P. A.; Bahsas, A. Tet. Lett. 1988, 29, 5855-5858.
Introduction: Reaction revisitedIntroduction: Reaction revisited
NXTFA
MeCN, r.t.
X
Grieco, P. A.; Bahsas, A. Tet. Lett. 1988, 29, 5855-5858.
Potential applications in total synthesisPotential applications in total synthesisHOOC Cl
N
OH NH OMe
VirantmycinMartinelline
O
NH
OHO
Helquinoline
y
NO
O
N
N
NO
HO O
ON
Isoschizogamine
CamptothecinDynemycin
Luotonin AMartinellic acidGalipinine
Outline• INTRODUCTION• REACTION INSIGHT
Outline
– MECHANISM– CONTROL OF REGIOSELECTIVITY– STEREOCHEMICAL OUTCOME
• ACYCLIC DIENOPHILE– MONOSUBSTITUTED– DISUBSITUTED
• CYCLIC DIENOPHILE• VARIANTS OF POVAROV REACTION• SINGLE ELECTRON MECHANISM• ASYMMETRIC CATALYSIS• CONCLUSIONS
Mechanism:Mechanism:
N
Mechanism: Concerted or stepwiseMechanism: Concerted or stepwise
Catalyst
R1=R2R R
Products that can be formed
by concerted mechanism
Mechanism: Concerted or stepwiseMechanism: Concerted or stepwise
Catalyst
R1=R2R R
Product that can NOT be formed
by concerted mechanismby concerted mechanism
Mechanism: Concerted or stepwiseMechanism: Concerted or stepwise
BF3.OEt2PhMe, r.t.
E d
+
ExoEndo Exo
Alves, M. J.; Azoia, N. G.; Fortes, A. G. Tetrahedron. 2007, 63, 727-734.
Mechanism: StepwiseMechanism: Stepwise
BF3.OEt2PhMe, r.t.
MeO MeO
NCO2Et
H
|+_BF3
N
CO2Et
H
Alves, M. J.; Azoia, N. G.; Fortes, A. G. Tetrahedron. 2007, 63, 727-734.
ExplanationExplanationNH2 H
NN
TFA
HCHOTFA, MeCN
++
HN
NH
MeCN
NH2 HN
TFA, MeCN TFA, MeCN+
Mellor, J. M.; Merriman, G. D.; Riviere, P. Tet. Lett. 1991, 32, 7103-7106.
ExplanationPhOH
Explanation
O NH2 O HNPh
O NH
TFA
MeCN+ ++
O O O
r.t. 1.5h 56% 39%
Reflux 1.5h 82% 17%
O NH2
TFA
O
MeCN+
Mellor, J. M.; Merriman, G. D. Tetrahedron. 1995, 51, 6115-6132.
Control of regioselectivityControl of regioselectivity
BF3.OEt2+ +
4
r.t. 70 min
80%
2
Crousse, B.; Begue, J.; Bonnet-Delpon, D. J. Org. Chem. 2000, 65, 5009-5013.
Rationale for control of regioselectivityRationale for control of regioselectivity
O
O
LA= Lewis Acid
Stereochemical outcomeStereochemical outcome• Acyclic dienophiles
•Monosubsitituted•Monosubsitituted•Disubstituted
•Cyclic Dienophile
Stereochemical outcome li di hilStereochemical outcome- acyclic dienophile
OMe
N CO Et
OMe
MeOBF3.OEt2PhMe, r.t.+ +
NH
CO2Et,45 min44% Cis Trans
Axial substituent
less favoredH H
Equitorial
NH
MeO
COOEtMeO
Alves, M. J.; Azoia, N. G.; Fortes, A. G. Tetrahedron. 2007, 63, 727-734.
substituent
more favoredCis Trans
Example from literatureExample from literature
InCl3 (10 mol%)
MeCN, r.t.
Entry R1 R2 R3 Time(h) Yield(%)
1 H OMe H 2 901 H OMe H 2 90
2 H Me H 2 71
3 H Me Cl 2 76
4 OMe H Cl 3 704 OMe H Cl 3 70
5 H Me OMe 2 72
6 H OMe OMe 2 80
7 Me Me Cl 3 79
Sridharan, V. Perumal, P. T. Avendaño, C. J. Menéndez, C. Org. & Biomol Chem 2007, 5, 1351-1353.
Example from literatureExample from literature
BF3.OEt2DCM, r.t.
Entry R1 R2 R3 Time(h) Yield(%) Cis:Trans1 H H H 2 98 98:2
Cis Trans
1 H H H 2 98 98:2
2 H H Me 2 96 96:4
3 H H OMe 2 90 96:4
4 OMe H OMe 3 94 98:24 OMe H OMe 3 94 98:2
5 H H Br 2 96 98:2
6 H H Cl 3 96 98:2
7 H H F 2 92 95:5
8 Me H H 3 89 90:10
Nikitina, E. V.; Kouznetsov, V. V.; Cruz, U. M.; Zubkov, F. I. Synthesis. 2007, 375-384.
Stereochemical outcome A li Di hilStereochemical outcome- Acyclic Dienophile
BF3.OEt2PhMe, r.t.
R= Aromatic, -OMe, -OAc
RR
H
R
R= Aliphatic, bulky group (-OTBS)
Alves, M. J.; Azoia, N. G.; Fortes, A. G. Tetrahedron. 2007, 63, 727-734.
R
R
Stereochemical outcome C li di hilStereochemical outcome- Cyclic dienophile
O NH
O
CO2Et
BF3.OEt2PhMe, r.t.
+ +
H
O
H
RR
H
Chelation fovored
Alves, M. J.; Azoia, N. G.; Fortes, A. G. Tetrahedron. 2007, 63, 727-734.
Sterically favored
Example from literature
OR4
Example from literature
NH
O
PhR1
R2
R3R4
CAN(5 mol%)MeCN, r.t.
+ + +
Entry R1 R2 R3 R4 Time(h) Yield(%) Cis:Trans1 H H H H 2 83 57:43
Cis Trans
1 H H H H 2 83 57:43
2 H H Cl H 2 80 55:45
3 H H Br H 1.5 79 55:45
4 H H F H 4 70 55:45
5 H H Me H 4 70 60:40
6 H Me H Me 4 75 55:45
7 Me H Me H 6 85 55:45
Sridharan, V.; Avendaño, C. J.; Menéndez, C. Synlett. 2007, 1079-1082 .
Outline• INTRODUCTION• REACTION INSIGHT
Outline
• VARIANTS OF POVAROV REACTION– ABC VS ABB TYPE REACTION
• SYNTHESIS OF MARTINELLINE– REVERSING THE REGIOSELECTIVITY
• SYNTHESIS OF LUOTONIN A– ALKYNYL DIENOPHILE
• SYNTHESIS OF CAMPTOTHECIN AND LUOTONIN A– DOUBLE POVAROV REACTION
• SYNTHESIS OF JULOLODINES• SINGLE ELECTRON MECHANISM• ASYMMETRIC CATALYSIS
CONCLUSIONS• CONCLUSIONS
ABB t tiABB type reaction
OGdCl3
(20 mol%)MeCN, r.t.
+ +
NH
Ph
A
eC , t
88%B C
InCl3(10 mol%)H2O, r.t.
85%
+ +
85%
A B B
Li, C.; Zhang, J. H. J. Org. Chem. 2002, 67, 3969-3971.
M h iMechanismIn+3 In+3
In+3
H2OOHO
N
In+3
OH
InCl3(10 mol%)H2O, r.t.+ +
A B B
Li, C.; Zhang, J. H. J. Org. Chem. 2002, 67, 3969-3971.
E l f lit tExample from literature
InCl3(10 mol%)H2O, r.t.
Entry R Temp Time(h) Yield(%) Cis/Trans
Cis Trans
1 Me r.t. 4 84 81:19
2 OMe r.t. 4 81 87:13
3 F r.t. 10 81 86:14
4 NHPh t 10 65 86 144 NHPh r.t. 10 65 86:14
5 CN r.t. 24 46 69:31
Li, C.; Zhang, J. H. J. Org. Chem. 2002, 67, 3969-3971.
E l f lit tExample from literatureCAN
(5 mol%)(5 mol%)MeCN, r.t.
Cis Trans
Entry R1 R2 R3 Time(min) Yield(%) Cis/Ttrans1 H H Et 60 75 89/11
2 H H nPr 60 73 91/92 H H Pr 60 73 91/9
3 H H nBu 60 76 91/9
4 OMe H Et 45 80 90/10
5 OMe H nPr 45 88 91/9
6 OMe H nBu 45 90 93/7
7 H Me Et 60 72 87/13
8 H OMe Et 120 75 85/15
Sridharan, V.; Avendaño, C. J.; Menéndez, C. Tetrahedron. 2007, 63, 673-681.
Application in total synthesisApplication in total synthesis
•Martinelline & Martinellic acid
Martinelline & Martinellic acidMartinelline & Martinellic acid• Source: Roots of Martinella iquitosensis (lowland Amazon rainforest plant) • Isolated by: Merck group1
Synthesis utilizing Povarov reaction= 6 (core synthesis= 4, total synthesis=2)
y g p• Biological evaluation: First non-peptide bradykinin receptor inhibitor2
Martinelline
M t i lli id
1Witherup, K. M.; Ransom, R. W.; Graham, A. C.; Varga, S. L.; J. Am. Chem. Soc. 1995, 117, 6682–6685.2Xia, C. F.; Heng, L.; Ma, D.; Tet. Lett. 2002, 43, 9405-9409.
Matrinellic acid
Martinelline & Martinellic acidMartinelline & Martinellic acid
Approaches other than Povarov reaction to build the key intermediate:
Ma, D. Xia, C. Jiang, J. Zhang, J. Org. Lett. 2001, 3, 2189-2191.
Ma, D. Xia, C. Jiang, J. Zhang, J. Tang, W. J. Org. Chem. 2003, 68, 442-451.
19 steps
18 stepsSnider, B. B. Ahn, Y. O’Hare, S. M. Org. Lett. 2001, 3, 4217-4220.
p9 steps
Approaches using Povarov reaction to build intermediate
Powell, D. A. Batey, R. A. Org. Lett. 2002, 4, 2913-2916.
13 steps2 steps
Xia, C. F. Heng, L. Ma, D. Tet. Lett. 2002, 43, 9405-9409.
Martinelline & Martinellic acid
Cb
Martinelline & Martinellic acid
CO2Me
NCbz
2NH
MeO2CN
Cbz
N
MeO2CN
Cbz
NHCbzNHCbz
MeCN, r.t.48 h
NH2HN
H
Cat. Pd(OH)2, H2r.t. 5 h
Dy(OTf)3 92% 85 : 15CSA 74% 11 : 89
89%
Powell, D. A.; Batey, R. A. Org. Lett. 2002, 4, 2913-2916.
Outline• INTRODUCTION• REACTION INSIGHT
Outline
• VARIANTS OF POVAROV REACTION– ABC VS ABB TYPE REACTION
• SYNTHESIS OF MARTINELLINE– REVERSING THE REGIOSELECTIVITY
• SYNTHESIS OF LUOTONIN A– ALKYNYL DIENOPHILE
• SYNTHESIS OF CAMPTOTHECIN AND LUOTONIN A– DOUBLE POVAROV REACTION
• SYNTHESIS OF JULOLODINES• SINGLE ELECTRON MECHANISM• ASYMMETRIC CATALYSIS
CONCLUSIONS• CONCLUSIONS
2 3 Disubsitution2,3-Disubsitution
BF3.OEt2r.t.
OO
O
NH
CF3
OBF3.OEt2
r.t.
2 3 Disubsitution2,3-Disubsitution
R
NH
R'
RS S
NH
R'
RSc(OTf)3
MeCN, r.t.NiCl2/NaBH4
THF
’
1
Entry R’ R Time(h) Yield(%) 1(Trans/Cis)1 p-(C6H4)CO2Me Ph 3 81 23/1
2 Ph Bn 1 ¼ 82 28/1
3 iBu Bn 1 66 1/13 iBu Bn 1 66 1/1
4 iBu Ph 1 64 2/1
Cheng, D.; Zhou, J.; Saiah, E.; Beaton, G. Org. Lett. 2002, 4, 4411-4414.
Application in total synthesisApplication in total synthesis
Another example of 2,3-Disubstitution
•Luotonin A
Luotonin ALuotonin A
• Source: Peganum nigellastrum (Chinese medicinal plant )1• Source: Peganum nigellastrum (Chinese medicinal plant )• Isolated by: Hano and co-workers2
• Biological evaluation: Cytotoxic antitumor alkaloid
Synthesis Publications using Povarov reaction: 2
1 Osborne, D.; Stevenson, P. J. Tet. Lett. 2002, 43, 5469-5470. 2Twin, H.; Batey, R. A. Org. Lett. 2004, 6, 4913-4916.
Luotonin ALuotonin A4 step total synthesis
i) Y(OTf)3 (3 mol%) AnilineMeCN, r.t. 12 h 97%
ii) HCl, MeCN, reflux, 1 h 78%
NaOEtEtOH78oC99%99%
Microwave, 7 min 85%
Osborne, D.; Stevenson, P. J. Tet. Lett. 2002, 43, 5469-5470.
Outline• INTRODUCTION• REACTION INSIGHT
Outline
• VARIANTS OF POVAROV REACTION– ABC VS ABB TYPE REACTION
• SYNTHESIS OF MARTINELLINE– REVERSING THE REGIOSELECTIVITY
• SYNTHESIS OF LUOTONIN A– ALKYNYL DIENOPHILE
• SYNTHESIS OF CAMPTOTHECIN AND LUOTONIN A– DOUBLE POVAROV REACTION
• SYNTHESIS OF JULOLODINES• SINGLE ELECTRON MECHANISM• ASYMMETRIC CATALYSIS
CONCLUSIONS• CONCLUSIONS
Alk l di hil
R1
COOEtS
S
Alkynyl dienophile
N R2
R1CF3SO3HDCM, r.t.
5min
Entry R1 R2 Yield(%)1 Me 4-NO2-C6H4 59
2 Me 4-MeO-C6H4 72
3 Me 4-F-C6H4 63
4 Me 4-Cl-C6H4 68
5 H 4-MeO-C6H4 71
6 H 4-F-C6H4 63
7 Cl 3,4-CH2O2-C6H3 59
8 Cl 4-NO2-C6H4 57
Wang, S.; Zhao, Y. L.; Zhang, W.; Liu, Q. J. Org. Chem. 2007, 72, 4985-4988
Application in total synthesisApplication in total synthesis
•Camptothecin•Luotonin A
CamptothecinCamptothecin• Source: Camptotheca acuminata• Isolated by: Wall and co-workers• Biological evaluation: Potent antitumour alkaloid
Wall, M. E.; Wani, M. C.; Cook, C. E.; Palmer, K. H., Sim, G. A. J. Am. Chem. Soc. 1966, 88, 3888-3890.
CamptothecinCamptothecin
Dy(OTf)3 (10 mol%)
MeCN, 16 h, 50oC
71%
NN
O
Precursor used in the formal synthesis of camptothecin
NH CN
Twin, H.; Batey, R. A. Org. Lett. 2004, 6, 4913-4916.
Luotonin ALuotonin A6 step total synthesisp y
Twin, H.; Batey, R. A. Org. Lett. 2004, 6, 4913-4916.
Luotonin ALuotonin A6 step total synthesisp y
NH2
+ Dy(OTf)3 (10 mol%)
MeCN, 24 h, r.t.
51%
Twin, H.; Batey, R. A. Org. Lett. 2004, 6, 4913-4916.
Outline• INTRODUCTION• REACTION INSIGHT
Outline
• VARIANTS OF POVAROV REACTION– ABC VS ABB TYPE REACTION
• SYNTHESIS OF MARTINELLINE– REVERSING THE REGIOSELECTIVITY
• SYNTHESIS OF LUOTONIN A– ALKYNYL DIENOPHILE
• SYNTHESIS OF CAMPTOTHECIN AND LUOTONIN A– DOUBLE POVAROV REACTION
• SYNTHESIS OF JULOLODINES• SINGLE ELECTRON MECHANISM• ASYMMETRIC CATALYSIS
CONCLUSIONS• CONCLUSIONS
JulolodinesJulolodinesFluorescent probes, photoconductive materials, potential antidepressants and tranquilizers.
HN
R1
R2
N
R1
R2R3
TFE, r.t. 35% CH2O,
TFE, 1 h
i-Prn-C5H11i-Pr
N
OEtEtO
72%
N
OEtEtO
N
OEtO
35%
Legros, J.; Croousse, B.; Ourevitch, M.; Bonnet-Delpon, D. Synlett. 2006, 1899-1902.
72%80%35%
Outline• INTRODUCTION• REACTION INSIGHT
Outline
• VARIANTS OF POVAROV REACTION• SINGLE ELECTRON MECHANISM• ASYMMETRIC CATALYSIS• CONCLUSIONS• CONCLUSIONS
Single electron mechanismSingle electron mechanism
NH
NR1
ONO+BF4
-
DCM, r.t.H
R2
Wu, L.; Zhou, Y. L.; Jia, X.; Li, R.; Liu, Z.Tet. Lett. 2005, 46, 8937-8939.
Single electron mechanismSingle electron mechanism
O
N
NR1
2
O
N
O
R2
N O
N
NR1
R2
OH
R2
Wu, L.; Zhou, Y. L.; Jia, X.; Li, R.; Liu, Z.Tet. Lett. 2005, 46, 8937-8939.
Single electron mechanismSingle electron mechanismN
1
O
NH
R1
R2
NO+BF4-
DCM, r.t.
Entry R1 R2 Time(h) Yield(%)1 OMe H 3 72
2 Me NO2 1.5 91
3 H OMe 2 89
4 H H 1 94
5 H NO 1 645 H NO2 1 64
6 Br H 1 95
7 Cl H 1 96
Wu, L.; Zhou, Y. L.; Jia, X.; Li, R.; Liu, Z.Tet. Lett. 2005, 46, 8937-8939.
Outline• INTRODUCTION• REACTION INSIGHT
Outline
• VARIANTS OF POVAROV REACTION• SINGLE ELECTRON MECHANISM• ASYMMETRIC CATALYSIS
– ASYMMETRIC METAL CATALYSIS– ASYMMETRIC METAL CATALYSIS– ASYMMETRIC BRONSTED ACID CATALYSIS
• CONCLUSIONS
Asymmetric metal catalysisAsymmetric metal catalysis
Catalyst
OH
NH
Ph NH
Ph
OH
OH53% Yield, no chiral induction
N
Yb(OTf)3 Catalyst =
Ishitani, H.; Kobayashi, S. Tet. Lett. 1996, 37, 7357-7360.
Screening of additiveScreening of additive
Catalyst
OH
NH
Ph NH
PhOH OH
E t Additi ( l%) T (oC) Yi ld(%) Ci /T % (Ci )
OH
OHCatalyst = , DBUYb(OTf)3 Additive =
Entry Additive (mol%) Temp.(oC) Yield(%) Cis/Trans ee% (Cis)
1 DTBP (100) 0 67 99/1 61
2 DTBMP(100) -15 82 >99/1 70
3 DTBP(100) 15 92 >99/1 71
Ishitani, H.; Kobayashi, S. Tet. Lett. 1996, 37, 7357-7360.
3 DTBP(100) -15 92 >99/1 71
Substrate scopeSubstrate scope
Yb Complex(10-20 mol%)
Additive (100 mol%)DCM, -15oC, MS4Ǻ
Entry R’ R Additive Catalyst Yield(%) Cis/Trans ee% mol% (Cis)
1 Ph Et DTBP 20 58 94/6 61
2 Ph Et DTBP 10 52 94/6 77
3 α Naphthyl Et DTBP 20 69 >99/1 863 α-Naphthyl Et DTBP 20 69 >99/1 86
4 α-Naphthyl Et DTBMP 20 74 >99/1 91
5 α-Naphthyl Bu DTBMP 20 80 66/34 70
Ishitani, H.; Kobayashi, S. Tet. Lett. 1996, 37, 7357-7360.
Substrate scopeSubstrate scope
NH
R'
Yb Complex(10-20 mol%)
Additive (100 mol%)DCM, MS4Ǻ HOH
Entry R’ R Additive Catalyst mol%
Temp. (oC)
Yield (%)
Cis/ Trans
ee% (Cis)
DCM, MS4Ǻ
mol% ( C) (%) Trans ( )
1 α-Naphthyl Dihydrofuran DTBMP 20 -15 90 91/9 78
2 α-Naphthyl Dihydrofuran DPP 20 -15 67 93/7 86
3 α-Naphthyl Cyclopentadiene DTBMP 20 -15 69 >99/1 68
4 Cyclohexyl Cyclopentadiene DTBMP 20* -15 58 >99/1 73
*Sc(OTf)3 used
Ishitani, H.; Kobayashi, S. Tet. Lett. 1996, 37, 7357-7360.
( )3
Explanation of enantioselectivityExplanation of enantioselectivityYb Complex(10-20 mol%)
Additive (100 mol%)Additive (100 mol%)DCM, MS4Ǻ
Ishitani, H.; Kobayashi, S. Tet. Lett. 1996, 37, 7357-7360.
Asymmetric Bronsted acid catalysisAsymmetric Bronsted acid catalysis
ORCatalyst(10 mol%)
NH
R'OH
Toluene
Akiyama, T.; Morita, H.; Fuchibe, K. J. Am. Chem. Soc. 2006, 128, 13070-13071.
Substrate scopeSubstrate scopeORCatalyst
(10 mol%)
T l NH
R'OH
Entry R’ R Temp. Yield(%) Cis/Trans ee(%) for Cis
Toluene
1 Ph Et -10oC 89 99/1 94
2 Ph nBu -10oC 82 99/1 96
3 Ph Bn 0oC 76 99/1 91
4 2-BrC6H4 Et -10oC 77 99/1 90
5 2-BrC6H4nBu -10oC 86 99/1 89
6 2-ClC6H4 Et -10oC 79 99/1 88
7 2-MeC6H4 Et 0oC 59 99/1 91
8 2-ClC6H4 Et 0oC 72 96/4 87
9 2-naphthyl Et 0oC 74 99/1 95
10 2 naphthyl nBu 0oC 80 99/1 8810 2-naphthyl nBu 0oC 80 99/1 88
Akiyama, T.; Morita, H.; Fuchibe, K. J. Am. Chem. Soc. 2006, 128, 13070-13071.
Explanation of enantioselectivityExplanation of enantioselectivityORCatalyst
(10 mol%)
T l NH
R'OH
Toluene
Akiyama, T.; Morita, H.; Fuchibe, K. J. Am. Chem. Soc. 2006, 128, 13070-13071.
Recent developmentsRecent developments
O NH
O
Catalyst
H
Woll, M. G.; Jacobsen, E. N. Manuscript in preparation
Recent developmentsRecent developments
ON
R' OCatalyst
ON
R NH
Catalyst=y
Entry R’ R Yield(%) Trans/Cis ee(%) for Trans1 H H 86 4:1 942 H OMe 90 3:1 883 H NO2 82 3:1 934 H Br 94 4:1 945 OMe H 92 3:1 93
Woll, M. G.; Jacobsen, E. N. Manuscript in preparation
6 Br H 85 5:1 91
Outline• INTRODUCTION• REACTION INSIGHT
Outline
• VARIANTS OF POVAROV REACTION• SINGLE ELECTRON MECHANISM• ASYMMETRIC CATALYSIS• CONCLUSIONS• CONCLUSIONS
ConclusionConclusion
•Highly regioselective reaction with good diastereoselectivity•Highly regioselective reaction with good diastereoselectivity.•Mild reaction conditions (mostly room temperature).•Potential to ability to generate 3 stereocenters at a time.•Good tool for building library of compounds.
•Future prospects•Work to be done in the asymmetric Povarov reaction.•Synthesis of natural products using asymmetric form of the reaction.