ACIEE 2004
Baran Group Meeting
Chelation-Controlled Intermolecular Hydroacylation: Direct Addition of Alkyl
Aldehydes to Functionalized Alkenes
Willis and coworkers; p. 340
Catalytic Generation of Indium Hydride in a Highly Diastereoselective
Reductive Aldol Reaction
Shibata, Baba, and coworkers; p. 711
R2
R1
Et3SiH,
InBr3 (cat.)
R2
R3 CHO
R1
O
EtCN, 0 °C
O
R3
O
RhI catalyst
O
intramolecular
hydroacylation
H
OTES
The application of this method to intermolecular cases often results in decarbonylation. Solution:
R1,
R2,
and
R3
can be alkyl or aryl.
X
O
RhI catalyst
R
InBr3 + Et3SiH
X
O
chelationcontrolled
intermolecular
hydroacylation
R
H
[dppe(Rh)]ClO4
(10 mol %)
DCE, 60 °C, 2 h
— TESBr
MeS
O
MeS
O
alkene
H
Br2InH
R1
R
R2
alkene
O
Et3SiH
product
MeS
O
OMe
methyl acrylate
O
R2
R1
R1
R3
O
O
OInBr2
MeS
R2
O
NMe2
dimethyl acrylamide
InBr2
O
styrene
MeS
O
Ph
R3 CHO
H
H
R3
MeS
O
phenyl vinyl sulfone
SO2Ph
InBr2
O
O
R2
methyl propiolate
MeS
O
CO2Me
ACIEE 2004
Baran Group Meeting
A Mild and Efficient Synthesis of Oxindoles: Progress Towards the Synthesis of
Welwiindolinone A Isonitrle
Wood and coworkers; p. 1270
Me
Efficient Asymmetric Hydrogenation of Pyridines
Glorious and coworkers; p. 2850
Cl
R4
R5
H
Me
Me
CN
R6
R3
N
Welwitindolinone A Isonitrile
S
S
S
O
cat. DBU;
Cl2CO, Et3N
H
Me
Me
H
O
S
Me
O
SmI2, LiCl,
— 78 °C
Me
S
H
Me
Me
O
71%
H
OCN
NH
N
H
•HCl
i-Pr
The starting materials for this transformation are made from the appropriate 2-halopyridine and the
Evans oxazolidinone using K2CO3 and CuI.
S
H
O
R3
O
R6
O
O
N
H
R5
N
H
O
i-Pr
R4
1) H2 (100 bar),
AcOH, catalyst
2) aq. HCl
O
O
Running the reaction in acidic medium is required for several reasons: 1) protonated pyridines are more
susceptible to reduction than are free pyridines; 2) the prodcuts could poison the hydrogenation catalyst
as the free amine; 3) protonation locks the conformation of the substrate as shown allowing for effective
enantiocontrol.
The aminal produced during hydrogenation decomposes to an iminium, which exists in equilibrium with
the eneiminium species, scrambling the stereochemistry at C3.
N
H
HN
Copper(I)-Catalyzed Asymmetric Hydrosilylations of Imines at Ambient Temperature
Lipshutz and coworker; p. 2228.
Asymmetric Catalytic Coupling of Organoboranes, Alkynes, and Imines with a
Removable (Trialkylsilyloxy)ethyl Group— Direct Access to Enantiomerically
Pure Primary Allylic Amines
Jamison and coworker p. 3941
TBSO
O
N
P
xylyl
xylyl
O
6 mol % CuCl, 6 mol % NaOMe,
6 mol % R-(—)-DTBM-SEGPHOS,
3 eq. TMDS, 3.3 eq. t-BuOH, r.t.
H
N
P
xylyl
R1
TBSO
xylyl
R
NH
R1
H
R
Et
5 mol % [Ni(cod)2]/L*
Et3B, (3 eq)
N
R
R
R2
R2
(2 eq)
X
X
t-Bu
OMe
O
Me
O
xylyl =
O
P
t-Bu
P
t-Bu
2
Me
O
OMe
t-Bu
2
8 examples with
ee's > 94%;
in all cases
examined the R
stereoisomer
was formed;
R group can be alkyl
or a benzofused ring;
EWG's and EDG's on
the aromatic ring
are tolerated
Alkyne component must be symmetric
unless either R1 or R2 is an aryl group.
R was limited to aryl or saturated rings
in the present study.
P
L*:
Ph
Ar
Fe
Ar = 2-(i-Pr)Ph
ee's range from
70% to 89%
ACIEE 2004
Baran Group Meeting
Stereospecific and Stereodivergent Constrcution of Quaternary Carbon
Centers through Switchable Directed/Nondirected Allylic Substitution and
Iterative Deoxypropionate Synthesis Based on a Copper-mediated Directed
Allylic Substitution
Breit and coworkers; p. 3786 and 3790
Rh-Catalyzed Amination of Ethereal Ca—H Bonds: A Versatile Strategy for the
Synthesis of Complex Amines
DuBois and coworkers; p. 4349
O
HN
O
S
O
RO
O
CuBr
R4MgX
R2
R1
R4 R2
Ph2P
M
R3
R4
R3
O
H
R1
* R3
H
CuI
Ph2P
R2 R4
R3
R1
R3
O
R2
O
H
R1
O
Nu
R2
R1
Formation of 1,4-Diketones by Aerobic Oxidative C—C Coupling of Styrene with
1,3-Dicarbonyl Compounds
Christoffers and coworkers; p. 6547
R4M
R2
O
S
Lewis acids: BF3•Et2O, Sc(OTf)3
nucleophiles: allyltrimethylsilane, thioketene acetals, enol silyl ethers
The diastereoselectivity observed is highly dependent on pre-existent stereochemistry.
O
PPh2
O
R1
O
O
R2
O
R2
HN
R1
PPh2
O
O
Lewis acid,
carbon nucleophile
R1
H
O
1) air, CeCl3•7H2O (10 mol %),
i-PrOH, styrene, r.t.
2) AcCl, py
O
Essentailly complete transfer of chirality (99%) is observed in most cases. Yiields generally range
from good to excellent.
O
Ph
OEt
* R3
M R4
O
CO2Et
Enantioselective Synthesis of Cyclopropanes by Aldehyde Homologation
Taylor and coworker; p. 6671
OH
Me
BrMg
CuBr•DMS
(0.5 equiv)
i-Pr
OPMB
CuBr•DMS
(0.5 equiv)
O(o-DPPB)
Et
N
O
Me
R
Me
Et
Me
Me
OPMB
Et
dr = 97:3
83%
O
Me
Me
Tf2O, 2,6-lut.,
—78 to —50 °C
Also applicable to N-alkyl, N-Boc crotylamines.
OPMB
Et
N(i-Pr)2
O
i-Pr
O(o-DPPB)
Me
Me
n-BuLi, (–)-sparteine;
Ti(Oi-Pr)4, RCHO
O
dr = 99:1
80%
Diastereoselectivity for the oxygen manifold is not complete
due to equilibration after product formation; this is not a
problem with the nitrogen analogue.
Yields are generally high.
Iterations can be carried out by ozonolysis (92% or greater), iodination (92% or greater), and
metal halogen exchange followed by exposure to the conditions shown above.
Me
H
R
CHO
H
ACIEE 2004
Baran Group Meeting
Asymmetric Total Synthesis of (—)-Nakadomarin A
Nishida and coworkers; p. 2020
A Formal Total Synthesis of (+)-Pinnatoxin A
Inoue, Hirama, and coworkers; p. 6505
Me
H
Me
O
HN
N
N
H
CO2
O
O
Me
Total Synthesis of Apoptolidin
Koert and coworkers; p. 4597
OH
HO
Me
OH
O
O
OH
O
Me
Me
O
MeO
Total Synthesis of Apoptolidinone
Sulikowski and coworkers; p. 6673
Me
Me
Me
OH
O
Me
O
H
Me
OH
MeO
HO
O
H
Me
HO
OMe
Me
Me
O
O
Me
Me
OH
O
O
HO
OH
OMe
Me
Me
OH
O
Me
O
Me
H
OH
MeO
HO
An Effecient Total Synthesis of Optically Active Tetrodotoxin
Isobe and coworkers; p. 4782
O
Me
H2N
O
O
OHO
OH
OH
OMe
Me
OH
HO
H
N
N
H HO
H
OH
ACIEE 2004
Baran Group Meeting
Structural Revision and Total Synthesis of Azaspiracid-1, Part 1: Intelligence
Gathering and Tentative Proposal
Nicolaou, Satake, and coworkers; p. 4312
Structural Revision and Total Synthesis of Azaspiracid-1, Part 2: Definition of the
ABCD Domain and Total Synthesis
Nicolaou and coworkers; p. 4318
Total Synthesis of (±)-Nominine, a Heptacyclic Hetisine-Type Aconite Alkaloid
Muratake and Natsume; p. 4646
N
H
O
H
O
H OH
O
Me
H
O HO
A Concise Asymmetric Synthesis of the Marine Hepatotoxin 7-Epicylindrospermin
Williams and coworker; p. 2930
H
H
NH
O
Me
H
Me
Me
O
HO2C
OH
H
Me
O
O
Me
H
O3SO
Me
Me
H
HO H
H
N
NH
N
NH
Total Synthesis and Configurational Assignment of (—)-Dictyostatin, a MicrotubuleStabilizing Macrolide of Marine Sponge Origin
Paterson and coworkers; p. 4629
Total Synthesis of (—)-Dictyostatin: Confirmation of Relative and Absolute
Configurations
Curran and coworkers; p. 4634
O
NH
OH
Synthesis of the C-1027 Chromophore Framework through Atropselective
Macrolactonization
Inoue, Hirama, and coworkers; p. 6500
H2N
Boc2N
HO
Me
OH
O
MOMO
HO
Me
Me
Me
Me
Me
O
O
Cl
O
OH
OTES
(synthesized)
O
Cl
OMe
O
HN
OPMB
OH
OTES
MOMO
OH
O
O
O
O
O
Me
O
OH
O
Me
OH
NMe2
(final target)
O
ACIEE 2004
Baran Group Meeting
Enantioselective Total Synthesis of Batzelladine A
Nagasawa and coworkers; p. 1559
A Highly Efficient Synthesis of Lamellarins K and L by the Michael Addition/
Ring-Closure Reaction of Benzyldihydroisoquinoline Derivatives with
Ethoxycarbonyl-b-nitrostyrenes
Ruchirawat and coworkers; p. 866
NH2
O
O
N
H
NH2
O
H
O
N
NH
N
N
Me
NH2
O
H
O
X
N
H
N
H
(CH2)8Me
X
X
NO2
EtO2C
TIPSO
OpMB
EtO2C
TIPSO
CO2Et
H
7
N
X
H
N
N
O
X
N
NaHCO3, MeCN, 70 °C
CO2Et
X
OpMB
7
O
X
X
X
1. LAH
2. CsF
H
1) TBSCl
2) Barton deoxygenation
CH2OTBS
H
N
N
7
1. Pd(OH)2, H2
2. A, HgCl2, Et3N
H
O
O
BocHN
NBoc
HO
OTBS
Me
O
R = H: Eriolanin
R = Me: Eriolangin
O
H
NHBoc
NBoc
OH
SMe
OH
7
N
OpMB
7
O
A:
OTBS
H
Enantioselective Total Synthesis of the Highly Oxygenated 1, 10-Eudesmanolides
Eriolanin and Eriolangin
Metz and coworkers; p. 5991
CH2OH
H
OpMB
O
HO
OpMB
PPh3, DEAD
7
N
R
OpMB
Me
NBoc
NBoc
i) MeLi, —78 °C
ii) LiCH2CH2Si(Me)2Ph, —78 to —20 °C
iii) ICH2MgCl, —78 to 23 °C
O
O
O
OH
HO
S
O
Me
SiR3
Me
ACIEE 2004
Baran Group Meeting
Synthesis of the Furanosteroidal Antibiotic Viridin
Sorensen and coworkers; p. 1998
An Efficient Synthesis of Lactacystin b-Lactone
Donohoe and coworkers; p. 2293
O
OH
MeO
Me
NH
Me
O
Me
O
O
1. Li, DBB,
((MeO)CH2CH2)2NH,
MgBr2, isobutyraldehyde
NBoc 2. Ac2O, py, DMAP
O
OTBS
I
1. cat. OsO4, NMO
2. PPh3, DBAD, MeI
NBoc
Me
HO
EtO2C
EtO2C
CO2Et
Me
AcO
OTBS
i-Pr2EtN, xylenes,
reflux; DDQ, r.t.
OH
O
O
Me
NBoc
Me
AcO
Me
1. cat. InCl3, NaBH4
2. TESCl, imid, DMAP
Me
Me
OTES
OTES
O
O
O
1. TFA
2. aq. NaOH
Me 3. BOPCl, Et3N
Me
NH
Me
TMS
TMS
CsF, allyl Br
OTBS
OTBS
mesitylene,
165 °C
Me
TESO
EtO2C
OH
O
O
Me
O
NBoc
Me
AcO
1. RuCl3, NaIO4
2. HF•py
3. LDA, HMPA, MeI
TESO
EtO2C
AcO
Me
Stereoselective Total Synthesis of (—)-Borrelidin
Theodorakis and coworkers; p. 3947
Me
Me
Me
Me
OH
O
O
O
OH
Me
O
RCM
NC
O
O
CO2H
OTBS
Me
O
O
O
1. n-Bu4SnH, Mo(CO)3(t-BuNC)3
2. I2
3. n-Bu4SnCN, Pd(PPh3)4, CuI
R
R
O
NC
R
R
NBoc
Me
Me
ACIEE 2004
Baran Group Meeting
Fully Stereocontrolled Total Syntheses of (—)-Cylindricine C and (—)-2Epicylindricine C: A Departure in Sulfonamide Chemistry
Ciufolini and coworkers; p. 4336
H
O
H
Stereocontrolled Total Synthesis of (+)-Streptazolin by a Palladium-Catalyzed
Reductive Diyne Cyclization
Trost and coworkers; p. 4327
Me
O
OH
n-C6H13
N
N
n-C6H13
N
OH
OH
H
O
O
Me
Me
TsO
Pd2dba3•CHCl3, HCO2H, Et3SiH
TBDPSO
MeO2S
OH
HN
MeO2S
1. PhI(OAc)2
2. TBDPSCl, imid
TsO
OTBS
H
HN
HN
N
OTBS
O
H
O
O
O
O
HO
K(TMS)2N, —100 °C
TBDPSO
O2
S
N
H
Enantioselective Total Synthesis of (+)-Milnamide A and Evidence of Its Autooxidation
to (+)-Milnamide D
Molinski and coworkers; p. 5951
TBDPSO
O2
S
N
H
1. PhSH, BF3•Et2O
2. Raney Ni
Me Me O
H
N
Me
NMe
Me
N
H
Me
Me
Me
N
O
Me
CO2H
Me
Me
O
1. t-BuLi, 1-octene oxide, BF3•Et2O
2. DMP
n-C6H13
O
TBDPSO
O2
S
N
H
1. DBU; bis(pinacolyl)
diboronate, CuCl, KOAc
2. Na(CN)BH3, AcOH;
H2O2, aq. NaOH
3. DMP
4. TBAF
Me Me O
H
Me
Me
MeN
O
SeO2, CHCl3, reflux
O
N
Me
HO
n-C6H13
OH
N
Ph
N
N
O
Ph
ACIEE 2004
Baran Group Meeting
Total Synthesis of Thiostrepton, Part 1: Construction of the Dehydropiperidine/
Thiazoline-Containing Macrocycle
Nicolaou and coworkers; p. 5087
Total Synthesis of Thiostrepton, Part 2: Construction of the Quinaldic Acid
Macrocycle and Final Stages of the Synthesis
Nicolaou and coworkers; p. 5092
O
S
N
O
H
N
N
H
Concise Total Synthesis and Structure Assignment of TAN-1085
Suzuki and coworkers; p. 3167
O
HO
OH
NH2
O
OH
O
N
N
H
S
Me
S
O
Me
Me
O
HN
OH
N
O
H
N
N
S
HO
N
H
Et
OMOM
O Me
Me
S
Me
OH
OH
S
N
R
HN
N
S
N
COCl
H2N
S
Et3N
H
N
EtO2C
N3
Me
BocN
O
Me Me
EtO2C
Me
O
Me Me
OMOM
—78 °C, SmI2; BzCl
BnO
N
BocN
BnO
MeO
CHO
CHO
OBz
H
S
OMOM
CO2Et
N
N
N
S
BnO
MeO
S
CO2Et
OTBS
1. desilylation
2. Swern [O]
R
Me
N
OBn
S
OMe
OMe
S
Me
S
MeO
then MeOTf
R
N
N
O
Me
OBn
OMe
OMe
N
N
BocN
O
N
S
Me
S
N3
N
Ag2CO3, DBU,
BnNH2
OTBDPS
BnO
OTBS
R
S
OMOM
Li
O
N
HN
OTBDPS
BnO
OH
S
Me
O
N
O
Me
O
Me
O
HN
EtO2C
N
H
O
Me
O
HN
NH
HO
H
N
N Me
N
O
O
OMe OH
BnO
OMe