The Chemistry of Larry E. Overman Application in Total SynthesisDistinguished Professor of ChemistryUniversity of California, Irvine http://faculty.sites.uci.edu/overman/!
Topic Review!!
Bern, May, 1st 2014!
Julien Pomarole!
Index"
Ø Introduction : !— About Larry E. Overman!— Overman Rearrangement!
Ø Prins-Pinacol type reaction!
Ø Iminium Chemistry!— Biginelli condensation!— Aza-Cope/Mannich rearrangement!
Ø Formation of quaternary carbon-center!— Heck-type Cyclization!— Radical pathway!
Ø Conclusion!
2
About Larry E. Overman"
Ø B. A. from Earlham College, Richmond, IND (1965)!Ø Ph.D from University of Wisconsin, Madison, WI
(1969)!Under the supervision of Pr Howard H. Whitlock Jr."
Ø NIH postdoctoral fellowship, Columbia University, New York, NY (1969-1971),!with Pr Ronald Breslow"
Ø Joined University of California, Irvine, CA (1971)!Ø 1971-1974: Assistant Professor"Ø 1974-1994: Full Professor"Ø 1994-currently: Distinguished Professor"!
!
3 http://faculty.sites.uci.edu/overman/!http://www.scienceblog.com/community/older/2003/C/2003436.html!http://pubs.acs.org/cen/awards/8106/8106awards.html!
• Allylic imidate rearrangement: Mumm and Möller (1937)!!!• Overman rearrangement (1974, allylic trichloroacetimidate rearrangement)!
Overman Rearrangement"
4 (1) Mumm, O.; Möller, F. Ber. 1937, 11, 2214–2227.!(2) Overman, L. E. J. Am. Chem. Soc. 1974, 96, 597–599.!(3) Overman, L. E. J. Am. Chem. Soc. 1976, 98, 2901–2910.!
m-xylene
reflux (140 °C)O NH
CCl3
O NH
CCl3
O NH
CCl3HgX2 cat.
or Pd(II) cat.
O NHCl3C
O NH
MX2
CCl3
O NH
MX2
CCl3
O N
MX2
CCl3
via
H
Overman Rearrangement"
5
OHN
CCl3
O∗∗
HN
CCl3COP-Cl (5 mol%)
DCMr.t, 18 hR R
OHN
CCl3
80%94% ee
OHN
CCl3
Ph83%
96% ee
OHN
CCl3
87%95% ee
NBn
Boc
OHN
CCl3
HO
84%80% ee
OHN
CCl3
73%95% ee
MeO
O
OHN
CCl3
80%94% ee
O
Overman, L. E.; Owen, C. E.; Pavan, M. M.; Richards, C. J. Org. Lett. 2003, 5, 1809–1812.!Anderson, C. E.; Overman, L. E. J. Am. Chem. Soc. 2003, 125, 12412–12413.!
Prins-Pinacol rearrangement Strategy Formation of high substituted tetrahydrofuran"
6
O
OHHO
O
OMe
O(–)-citreoviridin
O CHO
OHHO
(–)-citreoviral
O
HHO
H
O2CPr
H
AcO
asbestinin-1O
OH
HHO
H
H
H
C7H15CO2HO H
biarellin E
O
OH
HH
O
O
H
H
H
C7H15CO2
biarellin F
O RR
RRR
RR
R
• First example : Mousset and co-worker (1969)!
• Mechanism :!
• Overman’s condition (1987):!
Prins-Pinacol rearrangement Strategy Prins-Pinacol reaction"
7 Martinet, P., Mousset, G., Colineau, M. Acad. Sci. C. 1969, 268, 1303-1306.!Hopkins, M. H., Overman, L. E. J. Am. Chem. Soc. 1987, 109, 4748 "Overman, L. E., Pennington, L. D. J. Org. Chem. 2003, 68, 7143!
Prins-Pinacol rearrangement Strategy (–)-citreoviral synthesis"
8
SiMe2Ph
Me
1. TaCl5, ZnBenzene/DME
2. 163. NaOH, H2O
OH
PhMe2Si
OTBDPS
2 steps OTMS
PhMe2Si
OTMS
20
TMSOTf (0.1 eq)DCM, –30 °C
PhMe2Si
O
O
OTBDPS41%
O
SiMe2PhO
OTBDPS47%
Hanaki, N.; Link, J. T.; MacMillan, D.; Overman, L. E. Org. Lett. 2000, 2, 223–226.!
O
OTBDPS16
MeO OMe
OTBDPS20
Prins-Pinacol rearrangement Strategy (–)-citreoviral synthesis"
9
PhMe2Si
O
O
OTBDPSO
SiMe2PhO
OTBDPS
SnCl4 (1.2 eq)
DCM, –78 °C89%
13 steps
O CHO
OHHO
(–)-citreoviral
Hanaki, N.; Link, J. T.; MacMillan, D.; Overman, L. E. Org. Lett. 2000, 2, 223–226.!
Prins-Pinacol rearrangement Strategy Biarellin E and F syntheses"
10 Corminboeuf, O.; Overman, L. E.; Pennington, L. D. J. Am. Chem. Soc. 2003, 125, 6650–6652.!
O
OH
HH
O
O
H
H
H
C7H15CO2
biarellin F
O
OH
HHO
H
H
H
C7H15CO2HO H
biarellin E
Prins-Pinacol rearrangement Strategy Biarellin E and F syntheses"
11 Corminboeuf, O.; Overman, L. E.; Pennington, L. D. J. Am. Chem. Soc. 2003, 125, 6650–6652.!
OO
H
H
8 steps
TIPSOOH
HO
TMS
H
TIPSOOH
HO
TMS
H
CHO
TBDPSO
1. p-TsOH•H2O, MgSO4DCM, –78 to –20 °C
2. SnCl4 (0.1 eq), DCM–78 °C to rt
(84%, 2 steps)
O
TBDPSO TMS
TIPSO H CHO
H H
H
18 Steps
O
OH
HHO
H
H
H
C7H15CO2HO H
biarellin E
Dess-Martin Periodinate
DCM, rt79%
O
OH
HH
O
O
H
H
H
C7H15CO2
biarellin F
Prins-Pinacol rearrangment Strategy (+)-Sieboldine A synthesis"
12 Canham, S. M.; France, D. J.; Overman, L. E. J. Org. Chem. 2013, 78, 9–34.!
O
O
N OHO
(+)-sieboldine AOR"O
OR'OR
Prins-pinacolrearrangement OTMS
OR'OR"
Me
R3OOR2
Prins-Pinacol type Reaction(+)-Sieboldine A synthesis"
13
OTBDPSO
OPhOMe
19
OH
OMe
OPh
OTBDPS
17
+TMSO
OMe
OPh
OTBDPS18
+
OTMS
OPhOTBDPS
MeO
OMe
conditions
Canham, S. M.; France, D. J.; Overman, L. E. J. Org. Chem. 2013, 78, 9–34.!
OTMS
OPhOTBDPS
MeOOMe
M-X (L.A.)
–MOMe
TMSO
OTBDPS
OMe
A
X
OPh
Prins-Pinacol type Reaction(+)-Sieboldine A synthesis"
14 Canham, S. M.; France, D. J.; Overman, L. E. J. Org. Chem. 2013, 78, 9–34.!
OH
OMe
OPh
OTBDPS
17
– TMSX
TMSO
OMe
OPh
OTBDPS18
– HX
Prins
TMSO
OTBDPS
H
OPhX
B
OTBDPSO
OPhOMe
19
Pinacolrearrangement
Prins-Pinacol type Reaction(+)-Sieboldine A synthesis"
15 Canham, S. M.; France, D. J.; Overman, L. E. J. Org. Chem. 2013, 78, 9–34.!
OSiR3
OPhOTBDPS
MeOOMe
OTBDPSO
OPhOMe
19
conditions
O
O9 steps
51%OTES
OPhOTBDPS
Pinacol-terminated 1,6-enyne cyclization(+)-Sieboldine A synthesis"
16 Canham, S. M.; France, D. J.; Overman, L. E. J. Org. Chem. 2013, 78, 9–34.!Canham, S. M.; France, D. J.; Overman, L. E. J. Am. Chem. Soc. 2010, 132, 7876–7877.!
Pinacol-terminated 1,6-enyne cyclization(+)-Sieboldine A synthesis"
17 Canham, S. M.; France, D. J.; Overman, L. E. J. Org. Chem. 2013, 78, 9–34.!Canham, S. M.; France, D. J.; Overman, L. E. J. Am. Chem. Soc. 2010, 132, 7876–7877.!
OTES
OPhOTBDPS OTBDPSO
OPhconditions
72
+
OH
OPh
TBDPSO
73
Pinacol-terminated 1,6-enyne cyclization(+)-Sieboldine A synthesis"
18 Canham, S. M.; France, D. J.; Overman, L. E. J. Am. Chem. Soc. 2010, 132, 7876–7877.!
OTES
OPhOTBDPS
[Au]+
TESO
OPh
TBDPSO
[Au]+
J
O
OPh
TBDPSO
Et3Si
1,6-EnyneCyclization
[Au]
K
OH
OPh
TBDPSO
73
[3,3]
Heterocyclization
O
OPh
TBDPSOL
[Au]Et3Si 1
1'
3
3'
OTBDPSO
OPh
72
Pinacol
Shift
Pinacol-terminated 1,6-enyne cyclization(+)-Sieboldine A synthesis"
19 Canham, S. M.; France, D. J.; Overman, L. E. J. Org. Chem. 2013, 78, 9–34.!Canham, S. M.; France, D. J.; Overman, L. E. J. Am. Chem. Soc. 2010, 132, 7876–7877.!
OTBDPSO
OPh
72
10 Steps
10%
O
O
N OHO
(+)-sieboldine A
Iminium Chemistry Nucleophile-promoted iminium ion-alkyne cycliztn"
20
N
H OH
OHN
OH
OH
(+)-pumilotoxin A (+)-Allopumiliotoxin 339A
OHOH
H
Overman, L. E.; Robinson, L. A. J. Am. Chem. Soc 1992, 114, 368–369.!Caderas, C.; Lett, R.; Overman, L. E. J. Am. Chem. Soc 1996, 118, 9073–9082.!
N
R
OHOH
H
NH
R
HO
O
(CH2O)nX–
H+
X
Iminium Chemistry Nucleophile-promoted iminium ion-alkyne cycliztn"
21 Overman, L. E.; Robinson, L. A. J. Am. Chem. Soc 1992, 114, 368–369.!
HO10 Steps
19% OO
ON
OBnH
TsOH (3 eq)NaI (10 eq)
(CH2O)n (5 eq)
H2O/Aceton (10:1)100 °C, 2h81%
NOH
OH
OHOBn
H
I
1. n-BuLi (excess)THF, –78 °C to 23 °Cthen MeOH, 81%
2. Li (excess)liquid NH3, –78 °C3 min, 76%
NOH
OH
(+)-Allopumiliotoxin 339A
OHOH
H
Iminium Chemistry Nucleophile-promoted iminium ion-alkyne cycliztn"
22 Overman, L. E.; Robinson, L. A. J. Am. Chem. Soc 1992, 114, 368–369.!
OO
ON
OBnHH+
H2O OHOH
OHNH
OBnH
H+(CH2O)n
N
OBnH
R
OH
I– NOH
OH
OHOBn
H
I
3 Steps
51%OHOBn
O
Et O LDA, TBDMSClTHF/HMPA, –78 °C to 23 °C
then MeOH/HCl90% (7:1 dr)
MeO2C
OBn
Iminium Chemistry Nucleophile-promoted iminium ion-alkyne cycliztn"
23 Caderas, C.; Lett, R.; Overman, L. E. J. Am. Chem. Soc 1996, 118, 9073–9082.!
NH
OHH
OBnNaI
(CH2O)n, CSA
H2O, 100 °C60%
NOBn
OHH
I
1. n-BuLi (excess)THF, –78 °C to 23 °Cthen MeOH, 92%
2. Li (excess)liquid NH3, –78 °C3 min, 85%
N
H OH
OH
(+)-pumilotoxin A
7 Steps
54%
Iminium Chemistry Biginelli condensation"
24
NH
N
NH
HH
O
O
NH
N
NH
HH
C7H15Batzelladine F
NH
N
N
O
O
O
N NH2
OH
NH214
OH
H
O
(–)-Crambidine
McDonald, A. I.; Overman, L. E. J. Org. Chem. 1999, 64, 1520–1528.!Cohen, F.; Overman, L. E. J. Am. Chem. Soc. 2001, 123, 10782–10783.!Overman, L. E.; Rhee, Y. H. J. Am. Chem. Soc. 2005, 127, 15652–15658.!
NH
N
NH
NH
N
NH
O
OHN
NH2
H2NH H
(CH2)8CH3
Batzelladine D
Iminium Chemistry Biginelli condensation"
25
SNH
NH2 OH
R2
H
EtO
O
R
O O
R2 H2N NH
OMe
N
NH
OMe
O
EtO
R
R2
H+ cat.
SNH
H2NR2
OH
SNH
NR2
HP.T.
– H2O
O
R
OH
OEt
S
N NH
R2
OR
O
OEtH
N
HNS R2
OEt
O
RHO
6-exo-trigN
HNS R2
OEt
O
ROHH
H+
N
HNS R2
OEt
O
R
– H2ON
HNS R2
OEt
O
R
– H+
• Disocvery by Pietro Biginelli in 1891:!
!!• Mechanism :!
Biginelli, P. Ber. 1891, 24, 2962–2967.!Kappe, C. O. J. Org. Chem. 1997, 62, 7201–7204.!Hu, E. H.; Sidler, D. R.; Dolling, U. H. J. Org. Chem. 1998, 63, 3454–3457.!
Iminium Chemistry Biginelli condensation"
26
NH
N OHH
NH2
5
O
AllylO
O OTBDMS
6
NH
N
NH
HH
O
O
NH
N
NH
HH
C7H15Batzelladine F
NH
N
NH
HHO
OO
15
N
H2N NH2
HO C7H15
OHH
4
Cohen, F.; Overman, L. E. J. Am. Chem. Soc. 2001, 123, 10782–10783.!
Iminium Chemistry Biginelli condensation"
27
OH O
OMe
5 Steps
58%
NH2 NH2
OMe
OMe
NCbz
MeS OMe
DCM85% OMe
OMeNHHN
NCbz
H210% Pd/C
AcOH, MeOH98% OMe
OMeNHHN
NH 6morpholine
AcOH, Na2SO4
CF3CH3OH, 60 °C82%
NH
N
NH
HHOTBDMS
O
AllylO
O OTBDMS
6
4 Steps
54 % NH
N
NH
HHO
OO
15
BF4-
Cohen, F.; Overman, L. E. J. Am. Chem. Soc. 2001, 123, 10782–10783.!
Iminium Chemistry Biginelli condensation"
28
NH
N
NH
HHO
OO
15
4 morpholine, AcOH
Na2SO4, CF3CH2OH, 60 °C59%
BF4-
NH
N
NH
HH
O
O
NH
N
NH2
HOH
C7H15
4 Steps
14%
NH
N
NH
HH
O
O
NH
N
NH
HH
C7H15Batzelladine F
Cohen, F.; Overman, L. E. J. Am. Chem. Soc. 2001, 123, 10782–10783.!
N
H2N NH2
HO C7H15
OHH
4
Iminium Chemistry Biginelli condensation"
29 Kappe, C. O. J. Org. Chem. 1997, 62, 7201–7204.!McDonald, A. I.; Overman, L. E. J. Org. Chem. 1999, 64, 1520–1528.!
Iminium Chemistry Aza-Cope/Mannich rearrangement"
30
Aza-Cope rearrangement :!
Jacobsen, E. J.; Levin, J.; Overman, L. E. J. Am. Chem. Soc 1988, 110, 4329–4336.!
Iminium Chemistry Aza-Cope/Mannich rearrangement"
31 Knight, S. D.; Overman, L. E. J. Am. Chem. Soc 1995, 117, 5776–5788.!
7 Steps
46%
N
HO
OtBu
N NMe
MeN O
H
H+(CH2O)nNa2SO4
MeCN, 80 °C98%
O
N
OtBu
N
NMeMeN
O
Iminium Chemistry Aza-Cope/Mannich rearrangement"
32 Knight, S. D.; Overman, L. E. J. Am. Chem. Soc 1995, 117, 5776–5788.!
Me3Sn
OTIPS
OtBu
N
MeN
MeN
OI
Pd2dba3 (2.5 mol%Ph3As (22 mol%)
CO (50 psi), LiClNMP, 70 °C
80%N
MeN
MeN
O
TIPSO
OtBu
6 Steps
24%
N
N
O OH
H
H
(–)-strchnine[a]D25 = –139 (c =1.0, CHCl3)
Iminium Chemistry Aza-Cope/Mannich rearrangement"
33 Knight, S. D.; Overman, L. E. J. Am. Chem. Soc 1995, 117, 5776–5788.!
Iminium Chemistry Aza-Cope/Mannich rearrangement"
34
NHBocO
HO
1. CDI, HN(OMe)Me•HClDCM, rt, 94%
2. Me2C=CHMgBr, CeCl3THF, –78 °C, 94%
HNBoc
O 68 (0.2 mol%)H2
i-PrOH, rt HNBoc
HO
91% ee
Martin, C. L.; Overman, L. E.; Rohde, J. M. J. Am. Chem. Soc. 2010, 132, 4894–4906.!
NBoc
AcO
AcO
6 Steps
28%
2 Steps
73%
Iminium Chemistry Aza-Cope/Mannich rearrangement"
35 Madin, A.; O'Donnell, C. J.; Oh, T.; Old, D. W. Angew. Chem. Int. Ed. 1999, 38, 2934–2936.!
Iminium Chemistry Aza-Cope/Mannich rearrangement"
36
104 Steps
45%
[Pd2dba3]•CHCl3 cat.Ag3PO4, Et3N
THF, reflux70%
10 steps
23%
Madin, A.; O'Donnell, C. J.; Oh, T.; Old, D. W. Angew. Chem. Int. Ed. 1999, 38, 2934–2936.!
Quaternary Carbon-center formationHeck-type cyclization"
37 Overman, L. E.; Poon, D. J. Angew. Chem. Int. Ed. 1997, 36, 518–521.!
Quaternary Carbon-center formationHeck-type cyclization"
38
N
NNH
NH
Me
Me
(+)-calycanthine
NI Bn
O
N
O
OO
Bn ICO2Me
MeO2C
N
N
NH
NH
Me
Me
(+)-calycanthine
Overman, L. E.; Paone, D. V.; Stearns, B. A. J. Am. Chem. Soc 1999, 121, 7702–7703.!
Quaternary Carbon-center formationHeck-type cyclization"
39
CO2MeMeO2C
NI Bn
O
N
O
OO
Bn I6 Steps
15%
(Ph3P)2PdCl2 (10 mol%)Et3N, DMA
100 °C90%
NN
O Bn
O
Bn
OO
8 Steps
36%N
NNH
NH
Me
Me
(+)-calycanthine
N
N
NH
NH
Me
Me
(+)-calycanthine
Overman, L. E.; Paone, D. V.; Stearns, B. A. J. Am. Chem. Soc 1999, 121, 7702–7703.!
OTIPS
H
I
O
O
Pd(OAc)2 (30 mol%)PPh3 (60 mol%)
AgCO3
THF, refluxthen TBAF, THF, 23 °C
90% OH
O
OH
Quaternary Carbon-center formationHeck-type cyclization"
40
O
OTIPSO
O7 steps
44%
O
OTBDMS
1. LDA, 20% HMPA-THF, –78 °C2. TMSCl, –78 °C to 0 °C
3. HCl–H2O74%
O
OTIPS
HO
O
4 Steps
80%
Fox, M. E.; Li, C.; Marino, J. P. J. Am. Chem. Soc 1999, 121, 5467–5480.!
OBz
H
O
HHO2CHO
(–)-scopadulcic acid A
15 Steps
14%
OBz
H
O
HHO2CHO
(–)-scopadulcic acid A
Quaternary Carbon-center formationHeck-type cyclization"
41 Fox, M. E.; Li, C.; Marino, J. P. J. Am. Chem. Soc 1999, 121, 5467–5480.!
Quaternary Carbon-center formationHeck-Iminium Ion Cyclization"
42 Dounay, A. B.; Overman, L. E.; Wrobleski, A. D. J. Am. Chem. Soc. 2005, 127, 10186–10187.!
PPhPh
N
O
Pfaltz ligand
NH2
OTIPS
1. p-TsOH cat.Benzene, 50 °C, 95%
2. ClCO2Me, NaHMDSTHF, –78 °C, 56%
ON
O ON
MeO2C
OTIPS
1. Comin's reagent, NaHMDS,THF, –78 °C, 82%
2. 13, PdCl2(dppf)•DCM, THF, rtthen H2O2, 0 °C, 72%3. CsF, Cs2CO3, Comin's reagentDMF, rt, 95%
NMeO2C
OTf
NHBocPd(OAc)2 cat.
Pfaltz ligand cat.PMP, toluene, 170 °C
then CF3CO2HDCM, 0°C75%
NCO2Me
NBoc
99% ee
N N
Cl
OTf
OTfComin's reagent
B NHBoc
13
NH
N
HO
minfiensine
Quaternary Carbon-center formationHeck-Iminium Ion Cyclization"
43
NMeO2C
OTf
NHBocHeck-type
cyclizationNCO2Me
BocHN
H+
NCO2Me
BocHN
NCO2MeNHBoc
– H+
NCO2Me
NBoc
Dounay, A. B.; Overman, L. E.; Wrobleski, A. D. J. Am. Chem. Soc. 2005, 127, 10186–10187.!
NH
N
HO
minfiensine
Pd(OAc)2 cat.K2CO3, Bu4Cl, NaO2CH
DMF, 80 °C80%
NCO2Me
N
TESO
Quaternary Carbon-center formationHeck-Iminium Ion Cyclization"
44 Dounay, A. B.; Overman, L. E.; Wrobleski, A. D. J. Am. Chem. Soc. 2005, 127, 10186–10187.!
NCO2MeNBoc
5 steps
68% NCO2Me
N
TESO
I
8 Steps
30% NH
N
HO
minfiensine
NH
N
HO
minfiensine
Quaternary Carbon-center formationTertiary Radical pathway"
45 Schnermann, M. J.; Overman, L. E. Angew. Chem.Int. Ed. 2012, 51, 9576–9580.!
OMe
Me
Me
19(+)-fenchone
12 Steps
8%
H
Me MeH
Me
27
O
O
NPhth
H
Me MeH
Me
27
O
O
NPhth+
O
Cl
MeO2C
TBSO
28(1.5 eq)
29 (1.5 eq)[Ru(bpy)3](BF4)2 (0.01 eq)
DCMBlue LEDS, 2.5 h, rt
(61%)
H
MeH
Me
H Cl
MeO
MeO2CTBSO
H
30single
diastereoisomere
H
MeH
Me
Me
Aplyviolene
O
O
OAcO
Quaternary Carbon-center formationTertiary Radical pathway"
46 Schnermann, M. J.; Overman, L. E. Angew. Chem.Int. Ed. 2012, 51, 9576–9580.!
H
MeH
Me
Me
Aplyviolene
O
O
OAcO
H
MeH
Me
H Cl
MeO
MeO2CTBSO
H
30single
diastereoisomere
OHR1
R2R3
Et3NDMAP cat.
THF, 23 °C90%-quant.
O
ClO
N
O
O
Quaternary Carbon-center formationRadical Pathway"
47
O
R3
R1R2
O
O
ON
O
O
Ru(Bpy)3](PF6)2 (1.5 mol%)i-Pr2NEt•HBF4 (1 eq)
Hantzch ester (1.5 eq)Methyl vinyl ketone (1 eq)
THF/DCM, rtblue LEDs
R3
R1R2
O
O
OO
43%O
OO
OPhth
Ru(Bpy)3](PF6)2 (1.5 mol%)i-Pr2NEt•HBF4 (1 eq)
Hantzch ester (1.5 eq)Methyl vinyl ketone (1 eq)
THF/DCM, rtblue LEDs
O
82%
H
H
O
82%
O
22%
O
65%
O
O
Lackner, G. L.; Quasdorf, K. W.; Overman, L. E. J. Am. Chem. Soc. 2013, 135, 15342–15345.!
Quaternary Carbon-center formationTertiary Radical pathway"
48 Lackner, G. L.; Quasdorf, K. W.; Overman, L. E. J. Am. Chem. Soc. 2013, 135, 15342–15345.!
H
H
O
OMe
N
O
O
[RuI(bpy)3]+ [RuII(bpy)3]2+
*[RuII(bpy)3]2+NR3
[NR3]•+hυ
H
H
Me
H
H
MeOMe
O
NH
CO2EtH
Me
EtO2C
Me
H
NH
CO2Et
Me
EtO2C
Me
H
H
H
O
OMe
N
O
O
O
OMe
H
H
MeOMe
O
N
MeO2C CO2Me
Quaternary Carbon-center formationTertiary Radical pathway"
49
Okada, K.; Okamoto, K.; Morita, N.; Okubo, K.; Oda, M. J. Am. Chem. Soc. 1991, 113, 9401–9402.!Andrews, R. S.; Becker, J. J.; Gagné, M. R. Angew. Chem. Int. Ed. 2010, 49, 7274–7276.!Andrews, R. S.; Becker, J. J.; Gagné, M. R. Org. Lett. 2011, 13, 2406–2409.!Lackner, G. L.; Quasdorf, K. W.; Overman, L. E. J. Am. Chem. Soc. 2013, 135, 15342–15345.!
Conclusion"
Ø Differents strategies with highly stereo-control:!— Prins-Pinacol rearrangement.!— Aza-Cope/Mannich rearrangement.!— Biginelli condensation!— Heck-type cyclization!
Ø Amazing variety of natural product were synthetized in his lab.!!!
50 http://faculty.sites.uci.edu/overman/!
O
O
N OHO
(+)-sieboldine ANH
N
HO
minfiensine
NH
N
NH
HH
O
O
NH
N
NH
HH
C7H15Batzelladine F
H
MeH
Me
Me
Aplyviolene
O
O
OAcOO
OH
HH
O
O
H
H
H
C7H15CO2
biarellin F
N
N
NH
NH
Me
Me
(+)-calycanthineOBz
H
O
HHO2CHO
(–)-scopadulcic acid A
Conclusion on Larry E. Overman"
!Ø Overman’s Lab has completed synthesis of more of 80 complex natural
products and close to of 364 publication in major journal.!!Ø 2003 : ACS Arthur C. Cope Award!!
— "I hated chemistry in high school.” (Overman, 2003)!!— “I had absolutely no interest in chemistry until I was inspired by a great teacher
in college. What ultimately intrigued me was not only the idea of studying the natural world but also creating things that didn't exist before.” (Overman, 2003)!
51 http://faculty.sites.uci.edu/overman/!http://www.scienceblog.com/community/older/2003/C/2003436.html!http://pubs.acs.org/cen/awards/8106/8106awards.html!
52
END!