Wednesday, January 14, 2004
1
1. t-BuOCl, PhNH2;
Et3N (93%)
MeS
N
H H
O
OH
O
N
O
O
H
OTMB
OMe
(+)-longifolene
N
H
O
H
MeO2C
(+)-Paspalinine
2. RaNi, EtOH
O
O
O
Ryan Shenvi
Problems of the day:
Syntheses discussed:
N
H
JACS 1990
JACS 1990: A Snapshot of Modern Synthesis
Baran Group Meeting
desterpidine
2
1.
O
O
O
, 86%
2. MeLi, 65%
3. MnO2, 81%
O
H
O
OH
CO2H
OH
O
O
O
H
CO2H
glycinoeclepin
(±)-dactylol
MeO
OH
N
H
3
Me
1. Hg(TFA)2–HgO;
Et3NCl, 78%
HO
tazettine
O
2. Bu2SnH2, 81%
ClCH2CO2
ClCH2CO2
CO2Me
CO2Me
Partial list of transforms discussed:
Gassman indole synthesis
Moffatt Oxidation
Me
4
RhCl3 olefin isomerization (Grieco)
N
Bu
Wenkert Cyclization
Li
Ts
H
NTBS
1.
H
2. AcOH,
CF3CH2OH
H
H
Et
Bu
H
Saeguza-Ito oxidation
Luche Reduction
Myers Olefin Synthesis
Sharpless Allylic Amination
5
R3SiO
O
ArCO3H
–78 °C
R3SiO
CHO
Total syntheses of (+)-paspalicine and (+)-paspalinine
Amos B. Smith III, Toshiaki Sunazuka, Tamara L. Leenay, Jill Kingery-Wood;
J. Am. Chem. Soc. 1990, 112, 8197-8198.
1. LDA, THF;
HMPA, (MeS)2
88%
9 steps
O
O
O
9.4%
O
JACS 1990
Indole Alkaloids
Baran Group Meeting
O
Ryan Shenvi
Formal total synthesis of deserpidine . . .
Ellen W. Baxter, David Labaree, Herman L. Ammon, Patrick S. Mariano;
J. Am. Chem. Soc. 1990,112, 7682-7692.
CN
MeS
NC
OAc
2. t-BuOCl, PhNH2;
Et3N, 93%
1. NaOH, H2O
NTroc
2. HC(OEt)3,
EtOH, pTsOH
73%
110 °C, 5.5 days
40%
N
Troc
O
NH2 O
EtO
OAc
O
OEt
NTroc
1. Zn, EtOH
99%
2. nBuLi;
PhO2SO
N
SO2Ph
;
54%
MeS
EtO
1. RaNi, EtOH
2. p-TsOH, PhH, D
71%
3. p-TsOH,
MeCN, 0 °C
80%
O
NH2 O
O
O
H
N
O
O
N
O
O
N
SO2Ph
OtBu
N
SO2Ph
;
OEt
O
MeCN, 80 °C
2. LDA;
N
H
EtO
O
OEt
1. H2NNMe2, EtOH,
AcOH, 96%
BzOH, 50%
EtO
O
O
O
N
H
O
N
H
OH
NNMe2
O
O
N
H
2. DCC, TFA, Py,
DMSO, PhH
80%
O
O
H2O
64%
O
OtBu
O
1. K2CO3,
MeOH,
OAc
95%
N
H
HOAc
N
HClO4
76%
OAc
OEt
RhCl3, EtOH
70%
O
tBuCO2
N
H
H
O
(+)-Paspalicine
O
SeO2
44%
O
O
1. nBuLi, MeOTf
23% (3 steps)
N
H
H
NC
N
H
OH
O
(+)-Paspalinine
O
N
H H
2. BH3–THF;
NaOH, H2O2
H
2. 6% Na–Hg,
Na2HPO4
89%
OTMS
H2O–HOAc,
70 °C, 50 h
N
N
H
H
tBuCO2
H
NC
64%
OH
OMe
OH
O
1. Et3Al, TMSCN
H
N
SO2Ph
N
PhO2S
tBuCO2
N
N
PhO2S
N
H
1. NaOH, H2O2
2. HCl, 100 °C
3. CH2N2
H
NC
OH
OMe
N
H H
Advanced intermediate
N
H in Szantay synthesis
of desterpidine (R=TMB)
H
MeO2C
R=H
OR
OMe
Total synthesis of (±)-dactylol and related studies
Ken S. Feldman, Ming Jung Wu, David P. Rotella; J. Am. Chem. Soc. 1990, 112,
8490-8496.
O
hu
(>350 nm)
F3B
JACS 1990
New Routes to Aging Targets
Baran Group Meeting
Ryan Shenvi
. . .Total synthesis of . . . (±)-tazettine and (±)-6a-epipretazettine
Matthew M. Abelman, Larry E. Overman, Vinh D. Tran; J. Am. Chem. Soc. 1990,
112, 6959-6964.
O
OH
O
41%
H
1. Na, NH3 (liq.),
THF, EtOH
1. PhC(Me)2O2Li
O
BF3•Et2O,
–60 °C, PhCH3
2. LAH
74% (2 steps)
H
H
2. HO(CH2)2OH,
BF3•Et2O
3. PCC, NaOAc
63%
MeO
OH
OH
O
H2, Pd/C
H
2. 95 : 5 HMPA–H2O,
hu (254 nm)
50%
H
1.
OMe
3. Menthol
Chloroformate/
Resolution
4. LAH; MnO2, 81%
O
O
O
H
LDA, CdCl2
0 °C, 73%
(9:1)
BF3•Et2O, MeOH
O
1. 1N HCl, THF
H
67%
NHCO2Me
O
OMe
OAc
OMe
O
1. H2, Pd/C;
O
LAH, 95%
PhCH3, mw, 2.5 h
2. Ac2O, Py
74%
97%
no temp. given
OMe
O
H
O H
S
OH PhO
Cl ,
Py;
AIBN, nBu3SnH,
71%
OAc OMe
N
O
H
CO2Me
1. NaBH4, CeCl3
-78 °C, 95%
Cl ,
Py;
AIBN, nBu3SnH
50% (2 steps)
PhH, flow system
525 °C, 56%
MeO
(+)-longifolene
N
MeO
H
tazettine
Me
O
MeO
CO2Me
1. LAH, 98%
2. DMP, 73%
OH
N
H
1. LAH, 98%
2. TFAA, DMSO
61%
2. KH, MeI, 75%
3. CrO3–3,5-dimethylpyrazole
63%
O
O
H
O
O H
O
OAc
1. NaI, Et3N,
TMSCl
2. S
CO2Me
O
O
PhO
H
O
O
H
N
TMSO
O
O
O
Pd(OAc)2
O H
2. TMSOTf, Et3N
O
83%
H
Ag2CO3, THF
63–70%
O
O
O
O
NHCO2Me
O
O
O
2. MeLi, 65%
I
91%
O
O
, 86%
NH2
O
Direct total synthesis of (+)-longifolene via an intramolecular Diels-Alder strategy
Lei Bo, Alex G. Fallis; J. Am. Chem. Soc. 1990, 112, 4609-4610.
I
10% Pd(OAc)2
40% PPh3
O
MeCO2Cl
I
H
Cl
O
O
O
(±)-dactylol
O
O
1. AcCl, Py, 87%
-10 °C, CH3Ph HO
87%
HO
KH;
O
O
O
OH
O
2. LAH
72%
O
OH
NH2
1. TMSCN
O
OH
H
N
H
Me
6a-epipretazettine
Glycinoeclipin A and Aldol Methods
Baran Group Meeting
Total synthesis of glycinoeclepin A, E. J. Corey, Ioannis N. Houpis;
J. Am. Chem. Soc. 1990 112 , 8997-8998.
PhS
BuS
H
R=
OH
Ph
CO2R
O
1. RaNi, EtOH
85%
CO2R
BuS
SPh
89%
90% ee
83% de
Pd(PPh3)4
87%
Ts
O
O
OTf
Pd(OAc)2, PPh3
66%
CO2Me
BPSO
BPSO
O
O
CO2Me
H3C
O
HO
2. (ClCH2CO)2O
3. Cl3CCO2H
ClCH2CO2
82%
1. Hg(TFA)2–HgO;
Et3NCl, 78%
O
83%
O
OH
AcO
O
O
RCHO
t-Bu
OtBu
R
CH3
CH3
solvent
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
(+)-menthyl
(+)-menthyl
(+)-menthyl
(+)-menthyl
1:2 toluene-hexane
CH2Cl2
1:2 toluene-hexane
CH2Cl2
1:2 toluene-hexane
1:2 toluene-hexane
CH2Cl2
1:2 toluene-hexane
CH2Cl2
R*2B
O
R*2BBr
CO2Me
H3C
SPh
BPSO
% yield
93
90
81
91
82
91
86
83
80
anti:syn
% ee
98:2
96:4
99:1
96:4
94:6
99:1
98:2
99:1
97:3
94
89
98
97
75
87
94
95
96
O
OH
O
RCHO
SPh
OtBu
R
CH3
Reaction of Aldehydes with Thio Esters Promoted by Bromoborane Catalyst and DPEA To Form Syn Aldols
thioester
C6H5
C6H11
solvent
Ph
Ph
O+
O
+
% ee
93
86
1:99
1:98
97
91
R*2B
S
CH3
R*2B–
Br
S+ Ph
R*2B
O
O
CH3
anti:syn
Ph
t-Bu
O
R*2B–
Br
% yield
CH2Cl2
CH2Cl2
t-Bu
CO2H
+
O
OH
O
propionate ester
R
O
O
CO2Me
O
R
2. Bu2SnH2, 81%
3. K2CO3, MeOH
4. PDC, DMF, 92%
CO2Me
BPSO
FeCl3, AcOH,
Ac2O, CH2Cl2
CF3
C6H5
C6H5
(E)-C6H5CH=CH
(E)-C6H5CH=CH
cyclohexyl
cyclohexyl
cyclohexyl
C6H5CH2CH2
C6H5CH2CH2
H3C
O
S
Br O O
R*2BBr
OtBu
TESO
BPSO
1. F3CCO3H,
Na2HPO4
61–65%
1. NaHB(OMe)3
N
B
Reaction of Aldehydes with Propionate Esters Promoted by Bromoborane Catalyst and Triethylamine To Form Anti Aldols
CO2Me
TESO
O
95%
(3:1)
2. AIBN, Bu3SnH
Bu3Sn
84%
Ts
O O
CF3
Ph
R*2B
OMe
BPSO
N
S
O
2. DIBAL
3. BPSCl, Im, DMF
(91%, 2 steps)
BPSO
Ph
F3C
2. KHMDS,
PhNTf2
SnBu3•LiCl
1.
TfO
CF3
CO2R
Me
Ryan Shenvi
Versatile Catalyst for the Highly Enantioselevtive Synthesis of Either Anti or Syn
Ester Aldols, E. J. Corey, Sung Soo Kim; J. Am. Chem. Soc. 1990 112 , 4976-4977.
KHMDS, -100 °C,
O
JACS 1990
O
CH3
H3C
CO2H
glycinoeclepin
Differences in enolate geometry rationlized by competing rates of assisted bromide
dissociation and deprotonation
Olefination, Cycloaddition, Alkylation
Baran Group Meeting
Stereoselective Synthesis of Olefins from Silylated Sulfonylhydrazones,
Andrew G. Myers and Paivi J. Kukkola; J. Am. Chem. Soc. 1990 112 , 8208-8210.
R2(H)
RCHO
R
HN
R
H
TBSOTf,
N
Et3N, THF, -78 °C
R
NTBS
R2(H)
N
N
R
H
R1(H)
H
R
HH
N N
1
R (H)
H
H
R2(H)
organolithium reagent
aldehyde
R
R1(H)
H
N N
R1(H)
N
H
H
1.
H
2. AcOH,
CF3CH2OH
—N2
R
NH
R1(H)
Li
CHO
+
N
H
–O
O
Z2
R1
R2
R2
R2
SnCl4/ CH2Cl2
Z1
–70 °C
H
R1(H)
R2(H)
H
H
R1(H)
%yield (stereoselectivity)
CHO
H3C
Li
H3C
O
H3C
O
O
H
R2
t1, h
t2, h
ds
H
Me
H
Me
Me
CO2Me
CO2Me
H
H
CO2Me
H
H
CO2Me
CO2Me
H
Me
Me
Me
Me
n-OBu
Me
Me
Me
Me
H
7
7
8
8
1
0
0
2.5
3
0
>100:1
>100:1
6:1:1:8
20:1
>100:1
yield, %
68
72
76
78
80
(44%)
R3SiO
O
O
N
H
(85%)
OSiR3
OEt
OC
NC
O
2 Et
H
H
OSiR3
SeO2,
DMF, rt
OSiR3
79 (1:1)
(TsN)2Se
(90%)
,
O2
Se O
H2
TsHN
(51%)
81 (>20:1)
R3SiO
O
NHTs
(87%)
OSiR3
H
CH3
(25%)
Ts
NC
O
t
S, r
NB
Br
CH3
H
HO
86 (>20:1)
CH2CH3
Li
R2
New Trialkylsilyl Enol Ether Chemistry. Regiospecific and Stereospecific
Sequential Electrophilic Addition, Philip Magnus and Benjamin Mugrage; J. Am.
Chem. Soc. 1990 112 , 462-464.
H
Li
R
H
R1
90 (2:1)
83 (>20:1)
R1
R2
Z1
Z2
CH2CH2CH3
Li
CHO
R2
Z1
CH3
O
R2
PhCH3, 70 °C
O
H
CH3
R
O
Z2 O N
R
CH3
H3C
R2
H
77 (>20:1)
CH2CH3
O
R1
OSiR3
Li
H
O
Z2
H
CH3
+
N
Z1
H
CH3
CH3
–O
R2(H)
H
TDSO
Tandem [4 + 2]/[3 + 2] Cycloadditions: Facile and Stereoselective Construction
of Polycyclic Frameworks, Scott E. Denmark, Young-Choon Moon, C. B. W.
Senanayake; J. Am. Chem. Soc. 1990 112 , 311-315.
R
R2(H)
Ryan Shenvi
H
NTBS
TBS
R2(H) R
HH
NH
H
Ts
Li
Ts
Ts
N
JACS 1990
R2
Baran Group Meeting
JACS Total Syntheses of 1990
JACS 1990
Ryan Shenvi
Total syntheses of (+)-paspalicine and (+)-paspalinine, Amos B. Smith III, Toshiaki Sunazuka, Tamara L. Leenay, Jill
Kingery-Wood; 8197-8198.
Total synthesis of (.+-.)-isolobophytolide and (.+-.)-crassin by titanium-induced carbonyl coupling,
John E. McMurry, Russell G. Dushin; 6942-6949.
Total syntheses of (-)-histrionicotoxin and (-)-histrionicotoxin 235A, Gilbert Stork, Kang Zhao; 5875-5876.
The total syntheses of dl-zygosporin E and dl-C18-desmethylcytochalasin D, Edwin Vedejs, S. J. Wittenberger; 4357-4364.
General approach to the synthesis of macroline-related alkaloids. Stereospecific total synthesis of (-)-alstonerine, L. H.
Zhang, J. M. Cook; 4088-4090.
Total syntheses of (+)- and (-)-didemnenones A and B. Anti selectivity in the intramolecular carbomercuration reaction, Craig
J. Forsyth, Jon Clardy; 3497-3505.
Facile reduction of ethyl thiol esters to aldehydes: application to a total synthesis of (+)-neothramycin A methyl ether,
Tohru Fukuyama, Shao Cheng Lin, Leping Li; 7050-7051.
Asymmetric total synthesis of atisine via intramolecular double Michael reaction, Masataka Ihara, Makoto Suzuki, Keiichiro
Fukumoto, Chizuko Kabuto; 1164-1171.
Direct total synthesis of (+)-longifolene via an intramolecular Diels-Alder strategy, Lei Bo, Alex G. Fallis; 4609-4610.
Sequential radical cyclization approach to propellane triquinanes. Total synthesis of (.+-.)-modhephene, Craig P. Jasperse,
Dennis P. Curran; 5601-5609.
Total synthesis of (.+-.)-saframycin A, Tohru Fukuyama, Lihu Yang, Karen L. Ajeck, Richard A. Sachleben; 3712-3713.
Total synthesis of ionophores. 6. Asymmetric induction in the permanganate-promoted oxidative cyclization of 1,5dienes, David M. Walba, Claire A. Przybyla, Christopher B. Walker Jr.; 5624-5625.
Total synthesis of glycinoeclepin A, E. J. Corey, Ioannis N. Houpis; 8997-8998.
Formal total synthesis of deserpidine demonstrating a versatile amino-Claisen rearrangement/ Wenkert cyclization strategy
for the preparation of functionalized yohimbane ring systems Ellen W. Baxter, David Labaree, Herman L. Ammon, Patrick S.
Mariano; J. Am. Chem. Soc.; 7682-7692.
Total synthesis of (+)-latrunculin A, James D. White, Motoji Kawasaki; 4991-4993.
Total synthesis of both (+)-compactin and (+)-mevinolin. A general strategy based on the use of a special titanium reagent for
dicarbonyl coupling, Derrick L. J. Clive, K. S. Keshava Murthy, Andrew G. H. Wee, J. Siva Prasad, Gil V. J. Da Silva, Marek
Majewski, Paul C. Anderson, Claire F. Evans, Richard D. Haugen, et al.; 3018-3028.
Total synthesis of the tumor-associated Lex family of glycosphingolipids, K. C. Nicolaou, T. J. Caulfield, H. Kataoka, N. A.
Stylianides; 3693-3695.
Asymmetric, stereocontrolled total synthesis of (-)-brevianamide B, Robert M. Williams, Tomasz Glinka, Ewa Kwast, Hazel
Coffman, James K. Stille; 808-821.
Total synthesis of the oligosaccharide fragment of calicheamicin gamma 1, K. C. Nicolaou, Robert D. Groneberg, T.
Miyazaki, N. A. Stylianides, T. J. Schulze, W. Stahl; 8193-8195.
Total syntheses of (-)-nocardicins A-G: a biogenetic approach, Gino M. Salituro, Craig A. Townsend; 760-770.
Enantioselective total synthesis of neooxazolomycin, Andrew S. Kende, Kuniaki Kawamura, Robert J. DeVita; 4070-4072.
The total synthesis of dl-indolizomycin, Guncheol Kim, Margaret Y. Chu-Moyer, Samuel J. Danishefsky; 2003-2005.
Stereocontrolled total synthesis of (-)-anisatin: a neurotoxic sesquiterpenoid possessing a novel
spiro .beta.-lactone, Haruki Niwa, Masanori Nisiwaki, Itaru Tsukada, Takeshi Ishigaki, Shigeki Ito, Kazumasa Wakamatsu,
Tatsuya Mori, Megumi Ikagawa, Kiyoyuki Yamada; 9001-9003.
Total synthesis of calicheamicinone: a solution to the problem of the elusive urethane, Maria Paz Cabal, Robert S.
Coleman, Samuel J. Danishefsky; 3253-3255.
Asymmetric total synthesis of dibenzocyclooctadiene lignans (-)-schizandrin and (-)-isoschizandrin. Structure revision of (+)isoschizandrin, Alan M. Warshawsky, A. I. Meyers; 8090-8099.
Studies on Gelsemium alkaloids. Total synthesis of (+)-koumine, (+)-taberpsychine, and (+)-koumidine, Philip Magnus,
Benjamin Mugrage, Mark R. DeLuca, Gary A. Cain; 5220-5230.
Synthetic aspects of an asymmetric nitrogen-insertion process: preparation of chiral, non-racemic caprolactams and
valerolactams. Total synthesis of (-)-alloyohimbane, Jeffrey Aube, Yuguang Wang, Marlys Hammond, Mehmet Tanol, Fusao
Takusagawa, David Vander Velde; 4879-4891.
Total synthesis and structural investigations of didemnins A, B, and C Wen Ren Li, William R. Ewing, Bruce D. Harris, Madeleine
M. Joullie; 7659-7672.
Total synthesis of (+)-breynolide, David R. Williams, Paul A. Jass, H. L. Allan Tse, Ricky D. Gaston; 45524554.
The total synthesis of (+)-ionomycin, Stephen Hanessian, Nigel G. Cooke, Brad DeHoff, Yoji Sakito; 5276-5290.
Asymmetric tandem Claisen-ene strategy for steroid total synthesis: an efficient access to (+)-9(11)-dehydroestrone
methyl ether, Koichi Mikami, Kazuhiko Takahashi, Takeshi Nakai; 4035-4037.
Chemistry of tricarbonyl hemiketals and application of Evans technology to the total synthesis of the immunosuppressant (-)FK-506, Todd K. Jones, Robert A. Reamer, Richard Desmond, Sander G. Mills; 2998-3017.
A total synthesis of racemic paulownin using a type II photocyclization reaction George A. Kraus, Li Chen; 3464-3466.
Total synthesis of FK506 and an FKBP probe reagent, [C(8),C(9)-13C2]-FK506, Masashi Nakatsuka, John A. Ragan, Tarek
Sammakia, David B. Smith, David E. Uehling, Stuart L. Schreiber; 5583-5601.
Total synthesis of (+)-verrucosidin, Konghyun Whang, R. J. Cooke, Gurol Okay, Jin K. Cha; 8985-8987.
Enantioselective total synthesis of a protosterol, 3.beta.,20-dihydroxyprotost-24-ene, E. J. Corey, Scott C. Virgil; 64296431.
Total synthesis of (.+-.)-dactylol and related studies, Ken S. Feldman, Ming Jung Wu, David P. Rotella; 8490-8496.
Construction of quaternary carbon centers by palladium-catalyzed intramolecular alkene insertions. Total synthesis of
the Amaryllidaceae alkaloids (.+-.)-tazettine and (.+-.)-6a-epipretazettine, Matthew M. Abelman, Larry E. Overman, Vinh D.
Tran; 6959-6964.
The total synthesis of (.+-.)-epi-jatrophone and (.+-.)-jatrophone using palladium-catalyzed carbonylative coupling of
vinyl triflates with vinyl stannanes as the macrocycle-forming step, Albert C. Gyorkos, John K. Stille, Louis S. Hegedus;
8465-8472.
Stereoselective total syntheses of the antitumor antibiotics (+)-actinobolin and (-)-bactobolin from a common bridged
lactone intermediate,Ravi S. Garigipati, David M. Tschaen, Steven M. Weinreb; 3475-3482.
Total synthesis of the polyether antibiotic ionomycin David A. Evans, Robert L. Dow, Thomas L. Shih, James M. Takacs, Robert
Zahler; 5290-5313.
Total synthesis of the macrolide antibiotic cytovaricin, David A. Evans, Stephen W. Kaldor, Todd K. Jones, Jon Clardy, Thomas J.
Stout; 7001-7031.
Synthesis of (±)-marasmic acid via 1-oxaspirohexane rearrangement, Yoshito Tobe, Dai Yamashita, Tohru Takahashi, Masashi
Inata, Junichi Sato, Kiyomi Kakiuchi, Kazuya Kobiro, Yoshinobu Odaira; 775 - 779.
Enantiocontrolled synthesis of quaternary carbon centers via anionic oxy-Cope rearrangement: an efficient synthesis of (+)dihydromayurone, Eun Lee, In Jae Shin, Tae Seong Kim; 260 - 264.
Template-directed synthesis of (±)-allosamizoline and its 3,4-epimers, Barry M. Trost, David L. Van Vranken; 1261 - 1263.
Synthesis of the Antitumor Bisindole Alkaloid Vinblastine: Diastereoselectivity and Solvent Effect on the Stereochemistry of
the Crucial C-15--–C-18' Bond, Philip Magnus, Andrew Stamford, Mark Ladlow; 260 - 264.