JACS 1988: A Year in Review
Baran Group Meeting
Steven McKerrall
Notable Events in 1988
Publication Record (Total Synthesis):
-E.J. Corey Turns 60
-Beginning of the Human Genome Project
1988, vol 110
8744 Pages
1894 Total Papers
294 "Synthesis" Papers
1) Paquette, 16 (2)
2) Trost, 12 (2)
3) Danishefsky, 8 (7)
4) Nicolaou, 8 (5)
5) Myers, 5 (1)
6) Overman, 5 (1)
7) Yamamoto, 5 (0)
8) Corey, 4 (2)
9 Evans, 4 (1)
-CDs outsell Vinyl Records for the first time in history.
-Lockerbie Bombing
-Soviet Union pulls out of Afghanistan
-George H. W. Bush elected President
Synthesis Covered (cont.)
H
H
Comparative Molecular Field Analysis (CoMFA). 1. Effect of Shape on
Binding of Steroids to Carrier Protiens.
Cramer, 5959-5967
Most Cited Paper of the Year: 2186 Citations
Synthesis Covered
O
O
H3CO
OAc
OAc
H
N
H
AcO
H
O
O
H
(-)-Taxusin
Holton, 6558-6560
(+)-Asteriscanolide
Wender, 5904-5906
AcO
RO
H
H
O
N
O
MeO
( )-Pleurotin
Hart, 1634-1635
-Indolizidine 207A
Holmes, 8696-8698
OMe
( )-Lasubine II
Comins, 7445-7447
Cl
OH
O
OMe
O
O
OH
O
(-)-Taxol (semisynthesis)
Potier, 5917-5919
H
O
H
OAc
OH
(±)-Forskolin
Ikegami, 3670-3672
Corey, 3672-3673
H
OMe
O
O
H
PhCO2AcO
OH
N
OH
OH
HO
H
O
H
Sterpuric Acid
Paquette, 5818-5826
(+)-Strepurene
Okamura, 4062-4063
(±)-Laurenene
Wender, 4858-4860
O
(±)-Narwedine
Holton, 314-316
CO2H
H
AcO
O
O
OH
H
O
H
(-)-Laurenyne
Overman, 2248-2256
O
OH
OH
H
( )-Punctaporonin B
Kende, 6265-6266
HO HO
HO
HO
Ingenol
Funk, 3298-3300
Paquette, 6192-6204
O
N
H
( )-Mesembrine
Winkler, 4831-4832
HO2C
(+)-Streptolic Acid
Ireland, 854-860
JACS 1988: A Year in Review
Baran Group Meeting
Palladium Mediated Biomimetic Synthesis of Narwedine
Holton, R.A.; Makund, P.S.; Murphy, W.S. 314-316
A Synthesis of Taxusin
Holton, R.A.; Juo, R.R.; Kim, H.B.; Williams, A.D.; Harusawa, S.; Lowenthal,
R.E.; Yogai, S. 6558-6560
OH
H3CO
O
MTMO
Steven McKerrall
1) BF3 Et2O, TfOH
2) PDC
O
1) t-BuLi
+
2) tBuOOH, Ti(OiPr)4
NH2
1) CH3OH, then NaBH4
2) CH2O, NaBH3CN, MeOH
90%
O
O
H3CO
N
(±)-Narwedine
43% Overall
O
1) Li2PdCl4, Hunigs Base,
MeOH, -78 C
(-)-Patchino
NMe
2) Tl(OCOCF3)3
CH2Cl2/TFA 2:1, -10 C to 25 C
then PPh3
H3CO
48% over 2 Steps
2) Bu3SnH, AIBN
then H3O+
3) CrO3, H2SO4
82%
O
O
OH
mCBPA
OH
OH
then Ti(OiPr)4
90%
HO
tBuO2CO
Nickel-Catalyzed Intermolecular [4 + 4] Cycloadditions. 4. Enantioselective
Total Synthesis of (+)-Astericanolide
Wender, P.A.; Ihle, N.C.; Correia, C.R. 5904-5906
HO
O
O
1) Red-Al, Me3SnCl
2) n-BuLi, CO2
47%
O
OH
1) Red-Al, CuBr
H
98% ee
O
H
OH
OAc
2) BH3 THF, PCC
35%
(+)-Asteriscanolide
13 Steps
2.6% Overall
H
AcO
81%
(-)-Taxusin
22 Steps
93% Per Step!
20% overall
HO
O
OH
Ni(COD)2
H
O
1) FeCl3, Ac2O
2) Ts2O
3) NaOtBu
O
OTBS
4) LDA, mCPBA
5) Bu4NF, then Ac2O
6) Ph3PCH2
MEMO
50%
A Highly Efficient, Practical Approach to Natural Taxol
Denis, J.L.; et al. 5917-5919
1) TESCl
O
PPh3
67%
H
OAc
H
2) LAH/Darvon
4 Steps, 78%
AcO
1) DMSO, (COCl)2
8 Steps
O
tBuO2CO
HO
CHO
HO
HO
HO
S
O
Br
OH
O
O
1) Br
O
1) LDA, TMSCl
then, mCPBA
2) Red-Al
3) t-BuCOCl
86%
3) LDA, PhSeCl,
H2O2
83%
HO
98%
2) CH3COCl
3) DPC,
10-Deacetyl baccatin III
O
OH
H
HO
PhCO2 AcO
O
RO
Ph
O
AcO
NHBz O
HO
H
HO
PhCO2 AcO
H
O
OH
O
4) HCl
OEt
(-)-Taxol
61% Overall
JACS 1988: A Year in Review
Baran Group Meeting
Total Synthesis of (±)-Forskolin
Corey, E.J.; Jardin, P.S.; Rohloff, J.C. 3672-3673
O
OH
4 Steps
-Ionone
O
O
O
3) DBN
4) O2, hv,
Methylene Blue
52%
64%
AlHg
H2O/THF
97%
O
4.4 eq DIBAl
Toluene
-78 C, 75 min
O
OBz
CO2Me
OH
1) Bz2O
2) PCC
80%
H
H
OH
O
O
O
OH
O
CHO
1) PhSH (0.01),
O
OH
OH
Mechanism?
2) OsO4 (cat.)
Me3NO
73%
OMe
TBSO
6 Steps
AcO
41%
Me2NOC
5 Steps
O
O
hv
2% Methylene Blue
Sat O2, CHCl3
O
29%
O
H
O
55-63%
TBSO
O
O
OH
O
O
TBSO
O
Me2NOC
O
AcO
OAc
5 Steps
OH
(±)-Forskolin
31 Steps
1.52% Overall
H
81%
O
O
4) NaH, MPMCl
60%
O
O
H
O
O
O
H
67%
O
O
O
O
O
1) LiC CCH2CH2OTBS
2) MnO2
59%
3) Me2CuLi
4) 3N HCl
TBSO
OTBS
O
OO
2) AcOH/Ac2O
3) MeCuPBu3
68%
H
MeO
OH
O
O
O 1) NaOEt, PBu
3
OH
OH
OH
O
MPMO OHC
5 Steps
1) LAH
2) TrCl
3) OsO4
O
Mechanism?
O
OTr
OMPM
O
H
H
O
OMe Tol, 220 C
DMSO, 16 eq TEA
81%
O
O
O
H
O
O
O
MeOC=CCH2PPh3+
76% O
O
CH2SMe
OMe 15 eq SO3 Py
CO
3) AlHg
4) CH2N2
69%
1) tBuOOH
Mo(CO)6
85%
2) KOH
3) (OMe)2CMe2
A Total Synthesis of ( )-Forskolin
Hashimoto, S.; Sakata, S.; Sonegawa, S.; Ikegami, S. 3760-3762
1) LiC CCO2Me
CHO
3 Steps
O
O
2) Dihydropyran
TsOH
CH2OTHP
OMe
MeO
3) Me2CuLi
49%
4) TsOH
5) PCC
56%
O
1) TsC CCO2H
2) Me2CuLi, BF3—Et2O
Steven McKerrall
MPMO
OH
H
O
OAc
O
O
6 Steps
OH
OH
(±)-Forskolin
38 Steps
0.43%
46%
H
O
O
MPMO
PhSeCl
then Ra-Ni
OH
OH
78%
H
O
O
JACS 1988: A Year in Review
Baran Group Meeting
Total Synthesis of (-)-Laurenyne. Use of Acetal-Initiated Cyclizations to Prepare
Functionalized Eight-Membered Cyclic Ethers
Overman, L.E.; Thompson, A.S. 2248-2256
TMS
4 Steps TMS
L-(+)-DET
Br
TMS
Steven McKerrall
Synthetic Studies on Arene-Olefin Cycloadditions. 10. A Concise, Sterocontrolled
Total Synthesis of ( )-Laurenene
Wender, P.A.; von Geldern, T.W.; Levine, B.H. 4858-4860
O
tBuOOH, Ti(OiPr)4
78%
44%
OH
TMS
TBDPSO
1) Et3NHCl, Ti(OiPr)4
2) TsCl
60%
OTBDPS
Cl
EtO
SnCl4
NH3
81% ee
TMS
COO
84% brsm
OTs
1) H2/Pt
2) LDA,
OH
O
HO
O
O
I
TMS
Cl
O
1) (n-Bu)4NF
2) HF
OTs 3) PCC
4) TMSOTf, Pd(OAc)2
Cl
OTs
O
20% Over 5 Steps
1) DIBAl-H
2) MsCl, TEA
3) NaBH4
4) NaCN
5) DIBAl-H
29%
OHC
TES
TES
Cl
TES
n-BuLi
51%
O
nBu4NF
i) NBS, AIBN
ii) KOH
83%
72%
H
OH
Li, NH3
OH
HO
96%
H
94%
Cl
1) KHMDS, (Me2N)2POCl
2) Li, NH3
O
(-)-Laurenyne
20 Steps
0.56% Overall
O
OTs
O
CHO
O
3) LAH
hv
64% brsm
OTBDPS
Cl
1) Zn(BH4)2
2) TsCl
3) PCC
69%
Cl
OTs
PPTS (cat.)
98%
68%
OHC
O
OEt
OH
O3, Me2S, TEA
OH
(±)-Laurenene
14 Steps
5.07% Overall
36%
JACS 1988: A Year in Review
Baran Group Meeting
Sequential Annulation Approach to Sterpuric Acid and Sterpurene-3.12.14-triol,
Metabolites of the Silver Leaf Fungus Stereum purpureum
Paquette, L.A.; Lin, H.S.; Gunn, B.P.; Coghlan, M.J 5818-5826
3 Steps
MeO2C
+
Total Synthesis of ( )-Pleurotin and ( )-Dihydropleurotin Acid
Hart, D.J.; Huang, H.C. 1634-1635
CO2H
H
MeO2C
H
Ethylene MeO C
2
PhO2S
O
10 Steps
O
OMe
1) Xylene,
then, H3O+
2) CrO3, H2SO4
CH2OTBS
1) mCPBA
2) LDA
3) Li, EtNH2
4) CH2N2
5) (COCl)2
DMSO, TEA
44%
36%
O
O
Steps
O
H
H
HO
HO2C
O
HO
( )-Sterpuric Acid
Dowex-50
MeOH
OMe
52%
Over 2 Steps
( )-Sterpurenetriol
MeO
A Short Enantioselective Synthesis of (+)-Sterpurene
Okamura, W.H.; Gibbs, R.A. 4062-4063
HO
OMe
H
O
MeO
CH2OTBS
H
OMe
BF3 Et2O
OH
OH
CO2Me
1) 2,5-dimethoxyphenylMgBr,
CeCl3
2) SOCl2
3) LAH
4) (COCl)2, DMSO, TEA
34%
hv, -47 C
PhO2S
H
CH2OTBS
H
HO2C
SO2Ph
Steven McKerrall
CHO
MeO
H
OMe
I
4 Steps
H
CHO
60%
OH
CuI, Pd(PPh3)2Cl2
77%
O
O
32%
PhSCl, TEA
DCM, -78 C
70%
H
2 Steps
O
H
O
O
O
H
Mechanism?
H
HO
O
OMe
O
43%
O
( )-Dihydropleurotin Acid
0.89% Overall
MeO
SOPh
(+)-Sterpurene
8 Steps
13.9% Overall
O
H
6 Steps
( )-Pleurotin
29 Steps
0.43% Overall
H
MnO2, DCM, 48h, r.t.
48% brsm
Mechanism?
JACS 1988: A Year in Review
Baran Group Meeting
A Highly Stereocontrolled, Four-Step Synthesis of ( )-Lasubine II
Brown, J.D.; Foley, M.A. Comins, D.L. 7445-7447
O
CbzCl,
BrMg
OMe
OMe
N
Stereocontrolled Construction of an Ingenol Prototype having a Complete Array of
Oxygenated and Unsaturated Centers.
Paquette, L.A.; Ross, R.J.; Springer, J.P. 6192-6204
CuBr(SMe)2, BF3 Et2O
OMe
OMe
HO
Cl
OMe
OTBS
H
H
hv
O
O
O
Mechanism?
1) H2, Pd/C, Li2CO3
N
OMe
N
2) L-Selectride
66%
Cbz
1) NH2OH HCl
2) NaBH3CN
O
C8 Epimer displays
none of the biological
activity of the parent
Ingenol esters.
8
HO HO
HO
HO
OH
A Solution to the in,out-Bicycloundecan-7-one Problem Inherent in Ingenane Total
Synthesis
Funk, R.L.; Olmstead, T.A.; Parvez, M. 3298-3300
O-
Toluene,
R
1) K2CO3, MeOH
2) MsCl
R
3) Zn, AcOH
N
OH
N
AcO
MeO2C
O
H
H
H
H
N
N
N
N
H
TISOTf
O
O
( )-Indolizine 209B
22 Steps
7.82% Overall
H
MeO2C
O
O
TISO2C
Name Reaction?
( )-Indolizine 205A ( )-Indolizine 207A
16 Steps
15 Steps
18.2% Overall
18.2% Overall
89-90% Per Step!
HO
Ingenol Analogue
C8 Epimer
N+
AcO
H
HO
R
3) 4-acetoxybutanal
HO
O
OMe
Stereoselective Synthesis of ( )-Indolizidines 167B, 205A, and 207A.
Enantioselective Synthesis of (-)-Indolizidine 209B
Smith, A.L.; Williams, S.F.; Holmes, A.B.; 8696-8698
R
O
OMe
( )-Lasubine II
4 Steps
28% Overall
( )-Indolizine 167B
13 Steps
7.85% Overall
OTBS
O
EtOH
300 nm
O
OMe
H
OTBS
1) DIBAL-H
2) tBuOOH, VO(acac)2
3) PCC
4) H2, Pd/C
O
56%
Cbz
75%
H
MgBr
Cl
N
Steven McKerrall
JACS 1988: A Year in Review
Baran Group Meeting
A New Method for the Formation of Nitrogen Containing Ring Systems via the
Intramolecular Photocycloaddition of Vinylogous Amides. A Synthesis of
Mesembrine
Winkler, J.D.; Muller, C.L.; Scott, R.D. 4831-4832
4 Steps
MeO
MeO
52%
MeO
MeO
OMe
OTBS
O
8 Steps
1) Me3OBF4
2) DMAP
OH
1) (CH3)2CuLi
2) TsOH
N
H
N
H
O
H
OH
MgBr
O
1) LDA
2) PhSSPh
3) mCPBA
25%
OH
SO2Ph
O
O
O
O
O
EtO2C
1) DIBAl-H
2) TBSCl
3) LiDBBP
4) N
4 Steps
H
O
H
O
H
61%
NTs
O
O
H
80%
OTBS
Pd(PPh3)4
O
H
H
O
7 Steps
OBn
O
58%
OH
9.7%
OTBS
1) PCC
2) PPh3C(CH3)CO2Et
61%
CO2Et
2) TsOH
78%
( )-Punctaporonin B
14 Steps
0.73% Overall
74%
OH
OH
1) NaH, BrCH2CO2Et
OH
O
OCH3
O
Name Reaction?
O
OH
H
68%
O
O
H
Total Synthesis of ( )-Punctaporonin B
Kende, A.S.; Kaldor, I.; Aslanian, R. 6265-6266
O
O
1) BnOCH2Li
2) TBAF
3) (+)DIPT, Ti(OiPr)4
tBuOOH
OCH3
H
O
( )-Mesembrine
7 Steps
32% Overall
CO2tBu
78%
BnO
OH
OBn
84%
O
CO2Me
O
OMe
OMe
N
85%
75%
MeO
OMe
O
OBn
O
74%
O
MeO
3-Acyltetramic Acid Antibiotics. 2. Synthesis of (+)-Streptolic Acid
Ireland, R.E.; Smith, M.G. 854-860
O
O
1) LiHMDS, TBSCl
2) Benzene,
O
O
3) KF
4 Steps
H
OBn
OBn 4) CH3I
hv
N
H
Steven McKerrall
HO2C
Diphos
67%
O
O
(+)-Streptolic Acid
31 Steps
7.55% Overall
H
SO2Ph
LiDBBP: Lithium Di-tertbutylbiphenyl Radical Anion
JACS 1988: A Year in Review
Baran Group Meeting
Enantioselective Ring Clevage of meso-Epoxides with BHaloisopinocamphenylboranes
Brown, 6246-6248
X
HO
O
Ipc2BX
63-89% Yield
22-100% ee
R
R
R
Steven McKerrall
Natural Products Isolation
R
OH
Palladium Catalzed Carbonyltive Coupling of Aryl Triflates with Organostannes
Stille, 1557-1565
O
R1
O
R2
O
OTf
Pd(0), LiCl
R1
O
R2
(R3)3SnR2, CO
O
HO
Didemnenones
Fenical, 1308-1309
O
R1
Combrestatin D-1
Pettit, 8539-8540
Directed Reduction of -Hydroxy Ketones Employing Tetramethylammonium
Triacetoxyborohydride
Evans, 3560-3578
OH
O
O
OH
O
O
O
OH
Me4NHB(OAc)3
OH
OH
O
O
H
OR
OR
85% (50% Isolated)
Most Cited Or ganic Paper of the Y ear : 742 Citations
O
Me
O
H
N
H
H
N
H
Asymmetric Diels-Alder Cycloaddition Reactions with Chiral , -Unsaturated NAcyloxazolidinones
Evans, 1238-1256
O
H
Cephalostatin 1
Pettit, 2006-2007
O
O
OH
N
Me
AlEt2Cl
COXa
R
Endo:Exo ~60:1
~90% ee
OH
O
R
A Close Second: 641 Citations
Asymmetric Hetero-Diels-Alder Reaction Catalyzed by Chiral Organoaluminum
Reagent
Yamamoto, 310-312
SiAr3
OMe
Me
Me
2) CF3CO2H
TMSO
Me
O
OH
MeO
O
H
N
O
1) RCHO, cat
OH
Yield: 62-93%
67-97% ee
O
O
O
O
AlMe
R
O
OMe
O
Me
SiAr3
cat
Onnamide A
Higa, 4851-4853
JACS 1988: A Year in Review
Baran Group Meeting
Steven McKerrall
Notable Total Syntheses Covered Elsewhere
Additional Total Syntheses Not Covered
CO2Me
O
HO
O
HO
t-Bu
O
O
(±)-Methylhomosecodaphniphyllate
Heathcock, 8734-8736
O
Me
CO2H
H
O
OH
(±)-Ginkgolide B
Corey, 649-651
OH
H
Me
H
O
OH
O
OH
Me OH
O
Me
O
Et
OMe
H
N
O
O
O
O
N
OH
(±)-Coriolin
Curran, 5064-5067
O
(-)-Brevianamide B
Williams, 5927-5929
O
HN
O
H
NH N
OH
O
O
HN
H3CO
HO
(±)-Fredericamycin A
Kelly, 6471-6480
N
O
OH
OH
O
O
HO
O
O
Me
Me
(+)-X-206
Evans, 2506-2526
O
N
H
Me
OH
Me
H
OH
Me
OH
HN
O
Me
Me
Me
O
OH
OH
HN
HO
Me
O
OH
OH
OH
OH
O
HO
CO2H
N
H3CO
Me
OH
(+)-Amphotericin B
Nicolaou, 4660-4705
OR
NH2
O
(+)-CC-1065
Boger, 1321-1323
HO
HO
Prostagladins E, D, F, and I
Noyori, 4718-4726