Pericyclic reactions
Pericyclic reaction
• Concerted reactions with cyclic transition
states
(breaking and making of bonds occur
simultaneously )
• No intermediates
Pericyclic reaction
•
•
•
•
Cycloaddition Reactions
Electrocyclic Reactions
Sigmatropic Rearrangements
Ene Reactions
Cycloaddition Reactions
• Using electrons in π bonds
→ form two σ bonds and become one ring
• Diels-Alder reaction
C
(diene + dienophile)
• HOMO / LUMO
Selectivity in Diels-alder
• Exo < Endo
• Secondary orbital
interactions
exo
endo
If substituent is quite large…
Asymmetric Diels-Alder reaction
• Chiral catalyst
BINOL,VANOL,VAPOL
or Ti-BINOL…
• Recent Study
In this case they are using
Boron Compounds
Chiral ligand VANOL or VAPOL
BH3 THF AcOH
Good way to synthesis
some natural products
Xia Li, Jianguang Han, Alexander X. Jones, and Xiaoguang Lei J.
Org. Chem., 2016, 81 (2), pp 458–468
Up to 97% ee
Asymmetric Diels-Alder reaction
• Chiral catalyst
MacMillan’s Catalyst
CHO…useful
acrolein
R
Me
Pr
i-Pr
Ph
Furyl
yield
75
92
81
99
89
5mol% cat.
MeOH H2O
23℃
exo:endo
1:1
1:1
1:1
1.3:1
1:1
exo ee (%)
86 (2S)
86 (2S)
84 (2S)
93 (2S)
91 (2S)
Kateri A. Ahrendt , Christopher J. Borths , and David W. C. MacMillan
J. Am. Chem. Soc., 2000, 122 (17), pp 4243–4244
endo ee (%)
90 (2S)
90 (2S)
93 (2S)
93 (2S)
93 (2S)
Asymmetric Diels-Alder reaction
• Chiral catalyst
chiral oxazaborolidine
(R)-2-Methyl-CBS
-oxazaborolidine
Only 4mol% catalyst
For high yield and ee
4mol%
99% yield
94% ee
Duan Liu , Eda Canales , and E. J. Corey
J. Am. Chem. Soc., 2007, 129 (6), pp 1498–1499
Intramolecular Diels-alder
Intramolecular Diels-alder
• MacMillan’s Catalyst
(S)
Exo selective
Up to 20:1 selectivity
(R)
Endo selective
Joel F. Hooper, Natalie C. James, Esra Bozkurt, Viktorya Aviyente, Jonathan M. White,
Mareike C. Holland, Ryan Gilmour, Andrew B. Holmes, and K. N. Houk
J. Org. Chem., 2015, 80 (24), pp 12058–12075
Electrocyclic reactions
• Use one π bond to form one σ bond
(and become ring)
• Thermal and photochemical ways
Electrocyclic reactions
conrotatory
Δ
hv
disrotatory
Hv → electron be excited
Number of π Thermal reaction
bonds
Photochemical reaction
even
• A
conrotatory
disrotatory
odd
disrotatory
conrotatory
Can be explained by Woodward-Hoffman rule
example
Up to 15.7 : 1
Ashay Patel, Gregg A. Barcan, Ohyun Kwon, and K. N. Houk
J. Am. Chem. Soc., 2013, 135 (12), pp 4878–4883
Sigmatropic rearrangements
• one σ-bond is changed to another σ-bond
• Claisen rearrangement
keto-enol
tautomerism
Δ
Good way to get alcohol
• Cope rearrangement
Δ
examples
• Not real pericyclic…
10 mol% cat
AcOEt 0℃
2h
94% yield
92% ee
10 mol% cat
CH2Cl2
-50℃ 2h
68% yield
94% ee
Duffey, T. A.; Shaw, S. A.; Vedejs, E. J. Am. Chem. Soc. 2009, 131, 14-14. Joannesse, C.; Johnston,
C. P.; Concellon, C.; Simal, C.; Philp, D.; Smith, A. D. Angew. Chem. Int. Ed. 2009, 48, 8914-8918.
Fisher indole synthesis
• phenylhydrazine + aldehyde or ketone
(acid condition)
[H+]
[H+]
rearrangement
-NH3
indole
Nowadays, many other synthesis are reported
example
Not good example…
But these sigmatropic rearrangements are good for
asymmetric synthesis (well controlled, doesn’t affect)
7steps
3steps
Asymmetric hydrovinylation
99% yield 96% ee
4-Et-7-vinylindole
22% yield
Wang Liu, Hwan Jung Lim, and T. V. RajanBabu
J. Am. Chem. Soc., 2012, 134 (12), pp 5496–5499
Indole derivatives
• Many significant derivatives are reported
Biologically active
Ene reaction
• Using C-H σ bond to form new bond
(so not real pericyclic reaction?)
• Need high temp
• Lewis acid / metal catalyst → lower temp
At the end…
Pericyclic
• Medicine
• Natural products
Many have rings