Yuzuru Kanda
The Chemical Society of Japan (http://www.chemistry.or.jp/en/)
– Established in 1878 by Mitsuru Kuhara
– Japanese first and biggest chemical society
– World's 2nd biggest chemistry society
– 40,000 members
– Host of PacifiChem
Total Synthesis
Me
H
OHC
Me
H
– Written in English!
– Almost only Japanese publishes
– First issue came out in 1926
– Current inpact factor 2.22
– Total citations 995
– Articles published bebfore 1991 are open access
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– Due to WW II publication was suspended in 1945 and 1946
– Theoretical Chemistry, Organic chemistry, Physical chemistry,
Inorganic chemistry, Biochemistry, Applied chemistry, Material
chemistry etc...
Me OH
H
H
Me
H
H
OH
84%
H
82% in 2 steps
Saegusa
Me OTMS
Pd(OAc) 2
iPr
H
Me
H
H
1. DIBAL
2. O 2, Rose Bengal
hν then PPh 3
iPr
OH
Me
H
H
H
Me
O
R =H
R = Ms
iPr
iPr
1. Ac2O
2. Li, liq. NH 3
H
75%
Me OTMS
iPr
59% in 2 steps
Me
RO
OBn Me
Me
OTMS
H
DMF, THF
78%
H
Me
H
NHK coupling
CrCl3–LAH H
Me
H
1. Swern Oxidation
iPr
2. TMSOTf, Et 3N
Me
Me OTMS
iPr
1. KF, SiO2
2. KF, Florisil
H
OBn Me
Me O
H
iPr
H
H
H
This Review
– Cover 1990–1986; 20,822 pages
– Approximately 70% of papers dealed with organic chemistry
– Many Invited papers in 1988 (which are not covered by this review)
Jack D. Dunitz, Jack Halpern, Allen J. Bard, James Alexander Morrison,
Raphael David Levine, Barry Martin Trost, Gilbert Stork, Gerald Scott,
Robert Howard Grubbs
R =H
R = TMS
Me
53%
Me
OBn
Me
4 steps
and many Japanese journals...
Bulletin of the Chemical Society of Japan
Me
Me O
Publications
– Bulletin of the Chemical Society of Japan
– Chemistry Letters
– The Chemical Record
– Chemistry - An Asian Journal
– Asian Journal of Organic Chemistry
– ChemNanoMat
iPr
H
Δ
H
OBn
OR
H
H
Cl
Me
NHK coupling
CrCl2
iPr
Anual symbosyum in March
– 10,000 participants, 6,000 presentation
Mitsuru Kuhara
Group Meeting
9/26/15
BCSJ 5 Years Review: 1990–1986
91% in 2 steps
H
H
Me
Me
N. Kato, 1988, 61, 3231
Cycloaraneosene
Group Meeting
9/26/15
BCSJ 5 Years Review: 1990–1986
Yuzuru Kanda
Me
Me
Me
H
O
O
Me
H
O
Me
O
1. Ac2O, pyridine
2. p-TsOH, acetone
Me
OH
Me
Me
54%
O
Me
H
Me
Me
O
OAc
OH
Me
Me
54%
OH
I
O
OH
COOMe
4. OHC
OTHP
5
ether, 83%
COOMe
THPO
O
COOMe
HO
Me
THPO
1. MeSO 2Cl, DMAP
DCM, 92%
2. nBu 3SnH, DTBP
DCM, 90%
N
TsO Me
CuI, PnBu 3
nBuLi, RCHO
O
ether, 98–66%
n = 1,2
n = 1,2 nBu
R. Noyori, 1988, 61, 1299
O
O
H
O
O
MeO
TBSO
O
O
1. MeSO 2Cl, Et 3N
2. DBU
benzene, 87%
O
1. OsO 4aq, MNO
acetone, tBuOH
H 2O
O
2. TBAF, THF
3. CSA, DCM
H
O
O
F
R
O
MeO
TBSO
R = H, alkyl, Ph
Me
O
O
Et 3N, DCM
91%
Prostaglandin E 1
HO
3. AcOH, H 2O, THF
5 steps, 56% overall yield
Prostaglandin D1, E 2, F1 α, F 2α were also synthesized 92%
Key reaction
MeO
RO
O
N
MNO
91%
OH
O
O
R =H
R = TBS, 92%
1. OsO 4aq, MNO
acetone, tBuOH, H 2O
2. NaIO 4, H 2O
HO
O 3. Ag2CO 3, benzene
F
O
O
O
1. DIBAL, toluene
2.
Me
LDA, OHC
O
O
O
OH
Ph 58%
MeO
THF, 97%
MeO
TBSO
Me
O
O
THF, 82%
Jones
reagent
acetone
90%
O
O
O
1. KOH, ethylene glycol
2. p-TsOH, benzene
Me
N
H
MeO
RO
OH H. Nagaoka, 1990, 63, 3560
1. tBuLi
2. CuI, PnBu 3
3. THPO
O
HO
DCM, 56%
(combined yield)
LiAlH 4
OAc
O
O
m-CPBA
Me
Me
NH 2
Me
O
1. K 2CO3aq, MeOH
2. p-TsOH, O 2
O
O
H
OH
Me
Me
Me 93%
α–santonin O
O
AlEt3, Ph
57%
R =H
R = TBS, 95%
1. MeO
O
HO
O
O
O
O
O
MeO
O
O
AcO
TrClO4, SnCl2, MS4A
ether
O
2. TBAF, THF
3. Ac2O, DMAP
O
11%
MeO
TBSO
O
O
H
O
OMe
(+)-Phrymarolin I
E. Taniguchi, 1988, 61, 4361
Halogenation
R
S
NFPOTf
R
S
R1
Me
Me
O n = 1, 2
NFPOTf
mCPBA or NBS
R
DCM or THF
77–37%
S
F
R1
F
N
Br 2
Graphine
R
F
DCM or THF
87–39%
R1
Group Meeting
9/26/15
BCSJ 5 Years Review: 1990–1986
Yuzuru Kanda
DCM, rt
quant
Me
R
TfO
NFPOTf
R = alkyl, Ar
R 1 = H, alkyl, ester, amide
T. Umemoto, 1986, 59, 3625
Br
Br
H
R
H
Br
Br 2
DCM
2h
Br
R
Br
Br
R
H
Br
Br
H
Br
R
H
Br
Br
E selective
w/ Graphine: E/Z = almost intact
w/o Graphine: E/Z ~ 1:1
Graphine works as radical scavenger
M. Kodomari, 1989, 62, 4053
RO
NBS
Silica gel
RO
Br
example:
O
OMe
OMe NBS
R
Silica
CCl4, rt
99–66%
CCl4 tBu
rt, 74%
Br
Sterically hindered o- bromination
H (or Bn)
R = Ar, tBu, Het
O
R
R
AlX3, Ph Se Cl
DCM, 100–90%
100% p-selective
N. Kamigata, 1988, 61, 2226
Br
O
O 2N
KBr
S O
O
2
ArSO3Br
Br+ source
MeOH
H (or Bn)
R
Br
Br
OH Polymer–BTMA–Br 3
R
DCM, MeOH
99–91%
OH
OMe
M. Yoshida, 1990, 63, 3704
N
Me
Br
R = H, Me, MeO, X, NO 2, COOH, COOR, OH
R = OMe, OEt, OPh, NMe 2
X = Cl, Br
X
DCM, MeOH
99–71%
S. Kajigaeshi, 1987, 60, 2667
1987, 60, 1159
tBu
Neutral and basic silica gels gave better selectivity but poor yield
Results highly depend on brand of silica gel
H. Konishi, 1989, 62, 591
O
TBABr3
R
Me
Me
Br 3
BTMA–Br 3
S. Kajigaeshi, 1989, 62, 3373
OR
Me
R = Me, OMe, OEt
OR
Me
OR
BTMA–ICl 4
N
H
Me
AcOH
93–83%
R
OR
N
H
Me
R
I
O
HO
OH
n
n = 4, 60%
n = 5, 49%
O n= 6 mixture of lactone, ester, polyester
CCl4, Na 2HPO 4aq
or AcOH, AcONa
CCl4, Na 2HPO 4aq O
or AcOH, AcONa
n
R1
S
O
BTMA–Br 3
NaOH
R2
R1
n = 1, 2
NaBrO 3
HBraq (48%)
OH
OH
n = 1, 2, 3
O
O
CCl4 or AcOH
99–13%
n = 2-4
OH
OH
BTMA–Br 3 (1 eq)
NaOH
OH
OH
O
O
R
NaBrO 3
HBraq (48%)
R 1 CCl 4 or AcOH R
OH
O
R1
R1
99–72%
R, R 1 = alkyl, Ph
S. Kajigaeshi, 1986, 59, 747
H 2O
99–50%
S
n = 1, 67%
n = 2, 13%
S. Kajigaeshi, 1989, 62, 2585
R 2 R 1, R 2 = Alkyl, Ar
O
S. Kajigaeshi, 1989, 62, 3376
RuCl 3•nH 2O
TBAB
NaBrO
3
R 2 (or H)
OH
R2
R1
O
R1
R 2 (or H)
H 2O
DCM or DCE
99–40%
MeCN
89–19%
R 1, R 2 = alkyl, Ph
primary alcohol tolerated
K. Oshima, 1986, 59, 105
CHO
CCl4, H 2O
97–50%
BTMA–Br 3 (2 eq)
NaOH
R2
CAN (cat)
NaBrO 3
R1
n
O
DCM, 98–32%
Oxidation
O
R = alkyl, Bn
BTMA–Br 3
O
R = Me, OMe, OEt, Br, Cl
R 1 = H, Me, Ph
R
O
BTMA–Br 3
I
S. Kajigaeshi, 1988, 61, 600
R1
R1
R
CCl4,
Na 2HPO 4aq
11–99%
N
H
DCM, 96–73% R 1 N
N
OH
S. Kajigaeshi, 1989, 62, 1349
BTMA–ICl 2
O
BTMA–Br 3
S. Kajigaeshi, 1990, 63, 941
AcOH
96–67%
R = Me, OMe, OEt, OH
R1
Cl
N
H
BTMA–ICl 2, ZnCl2
R
Group Meeting
9/26/15
BCSJ 5 Years Review: 1990–1986
Yuzuru Kanda
OH
COOH
Benzyl or Allyl
ImDC
CHO
NH
N Cr2O 7
H
DMF, rt
94–58%
ImDC
Primary OH tolerated
S. Kim, 1986, 59, 3297
S. Kajigaeshi, 1989, 62, 3748
O
O
SPh
silica–gel
purification
NCS
NH 2
O
H
N
OHC Ph
CCl4 (dry)
89%
SPh
EtOH
rt
R
EWG
R1
EWG, H, alkyl
N
H
TFAA
N
OH
R = alkyl, Ph
R 1 = alkyl, Ph, Het
O
NH 2
TFPA
AlCl3,
R
R O
H
N
Ph
or
Mild TFA source
Mild dehydration reagent of
aldehyde oxime and amide
O
THF or MeCN, reflux
61-100%
R CN
F 3C
O N
H
OH
N
H
O
R
MeCN, 100–26%
α, β-Unsaturated
ketones
THF
tBu
tBu
O
O
Me
Me
Product
tBu
Al
tBu
Me
MAD
Pt on silica
C10H 21
hexane
Si
Si Si
Pt
silica
Alkyl-Modified Catalyst
H2
COOH
O
O
O
Me
Me
COOH
K. Kuno, 1990, 63, 3320
CO, Se
DBU
O
R2
H 2O, 93–71%
O
R1
R2
O
Me
hexane or EtOH
R1
EWG (or H)
H. Chikashita, 1986, 59, 1747
Reduction
ClMe2Si
R1
R1
Me
MAD
LinBuiBu 2AlH
EWG
O
N OH R
R
R
H. Chikashita, 1987, 60, 737
Me
R1
CF 3
ether
99–90%
O
F 3C
O
Ph
Ph
R = alkyl, H
R = alkyl, Ar, Het
O
ROH
H
N
N
NH 2
H. Kakisawa, 1987, 60, 4369
water in silica–gel deprotected ethylene glcol and succinimide removed Cl
N
Group Meeting
9/26/15
BCSJ 5 Years Review: 1990–1986
Yuzuru Kanda
R 1 = alkyl, Ph, Het, EtOOC
R 2 = alkyl, Ph, OH, OEt, CN
Other double bonds tolerated
Ph
Me
tBu
1,4-reduction
68
76
0
0
1,2-reduction
0
0
74
99
sterically less demanding carbonyl was reduced even in presence of MAD
K. Maruoka, 1988, 61, 2241
N. Sonoda, 1989, 62, 1682
O
R
wet ZrO2
iPrOH
OH
R 1 (or H)
R
R 1 (or H)
R, R 1 = alkyl, Ph hexane, 99–58%
Ar
MeCN
I
R1
TMSOH
TMS
R
Ar
I
HI
R1
I2
(TMS)2O
I
CF 3NO
R1
Ar
CF 3N
N
R1
hν, 89–16%
Ar
R OH
R SH
R S R
RF
Sulfonium salt
K 2CO3
e.e. 11.9–4.1%
Me
Me
DCM, 65–18%
e.e. 25.0–4.7%
hν, 89–16%
R2 O
ClO 4
R1
S
R2
OMe
R 2 = Me, Et, Allyl
Salfonium salt
K 2CO3
OMe
S
RF
O
R1
R ORF
R SRF
COOH
OMe
Me
R2
EWG
H 2N
H
COOH
etc...
R
O. Tsuge, 1987, 60, 4079
1987, 60, 3347
1987, 69, 3359
O
R1
anti product
eM R1
O
Ph
e-
M R1
O
e-
O
R2
S
Ph
R1
R2
O
O
S
R2
R2
MO
E selective
Regardless of SM's
chirality
K. Yamakawa, 1989, 62, 2942
Ph
R 2 = Bn, Allyl
H. Matsuyama, 1989, 62, 3026
Ph
O
R3
R2
R 1, R 2 = alkyl, Ph
R1
OH
ether, 80–52%
OMe
OBn
Sulfonium salt
N
O
H
N
1. Me 2CuLi
2. ZnCl2
3. R 3CHO
R2
S
O
OBn
R2
O
COOH
O
PhOS
EWG
N
azomethine ylide sources
O
R 1 = Me, Et, Ar
R 2 = Me, Et, Allyl
O
Me
BnO
R
R
Chiral Control
N
TNSRF in MeCN
O
OMe DCM, 89–71%
O
H
N
R = alkyl, amide, carboxylic acid
R 1 = H, alkyl, OMe, CN, Het
O
N
RF = CF 3; TNSTf
RF = nC 4F 9; TNSNf
TNSRF in MeCN
O
O
OH
DMF, Et 2O
O
F 3C
PhMe
100–29%
R1
R2
O
O
CF3SO2F or nC 4F 9SO2F
NaH
DIPEA
O
S
Other Reactions; Original Reagents
NH 4OH
(H or) R 1
HI T. Sakai, 62, 1989, 3537
active species
COOH
R (or H)
R1
N
R1
HN
R
Ar
R2
EWG R
R2
M. Shibagaki, 1988, 61, 3283
Ar
R 1 hexane, 99-42%
EWG
Very mild reduction
Double bonds survive
H
OTMS
R
OH TMSCl, NaI, MeCN
R
Group Meeting
9/26/15
BCSJ 5 Years Review: 1990–1986
Yuzuru Kanda
TiCl2(iPr) 2, Chiral diol
MS4A, TMSCN
R
H PhMe, 96–67%, 96–61%ee
R = alkyl, Bn, Ar
HO
R
H
CN
Ph
Ph
O
OH
Me
O
OH
Ph
Ph
Chiral diol
K. Narasaka, 1988, 61, 4379
Other Reactions
Me
O
O
COOR*
OR* SnCl4,
Cl Quinine
R*O
Cl
R
COOR*
DCM, –40 ºC Me
70%, 99%ee
H. Suzuki, 1988, 61, 1999
O
O
X
R1
OH
CHO
OH
Br
1.tBuLi
2. MgBr 2
O
H+
O
DMF, rt, 100–60%
R1
R1
R2
R2
OH
O
Ph
NHPh OHC
COOMe
OMe
MeOOC
OMe
COOMe
N
R
Ph
R =H
R = Ts
66%
H
THF, rt
92%
R2
R1
H 2SO4
THF, 82%
R
COOMe
NPh
N
DME, 92–54%
R
R
OH
OH
4
BiCl 3, Fe
BF 3•OEt 2
O
Li O
N
SnBrCl2
:
1
M. Iyoda, 1989, 62, 3380
NPh
ether
95%
SnBrCl2
69–7%
Br
N
H
S. Torii, 1987, 60, 1951
HCOOH
or HCOOH–Ac 2O
O
H. Yamamoto, 1989, 62, 3736
SiO2
R
R
d.r. = 94:6–60:40
R 1 = tBu, Cy, Ar
R 2 = H, Me
N
R1
O
O
O
91–34%
H
R2
SnCl2•2H 2O
LiI•3H 2O
Br
O
PhMe, ether
benzene
quant
O
BrMg
R1
Pb, Bu 4NBr, TMSCl
or PbBr 2, Al
R
O
Br
Group Meeting
9/26/15
BCSJ 5 Years Review: 1990–1986
Yuzuru Kanda
MeO
MeOH MeOOC
89%
N
COOMe
N
R
Br
Ph
All products were obtained
as a single diastereomer
S. Kanemasa, 1990, 63, 2857
OH
X
R3
OH
Milder than Grignard reaction
Bi, BiCl 3–Zn, BiCl 3–Al are usable
R
Me
M. Wada, 1990, 63, 1738
cis selective
Na 2CO3 R1
DCE
R 1 = Ph, EtOCO,
R 2, R 3 = h, alkyl, Ph
X = Morpholino, BuO, PhO, TMSO
R2
N
O
R 3 DCE
X
R2
Fe 3(CO)12
R1
99% in 2 steps
N
H
R3
TFA
DCE, <78% in one pot
S. Nakanishi, 1990, 63, 3595
O 2N
R2
NO 2
O
O
SMe
MeOH
2NH3
N
O 2N
NO 2- NH +
4
R2
upto 90%
R1
N
Me
HN
R1
O
R
O
TES
R
TMS
Nu
Nu = TESCl
Perfect Z selectivity
TMSO
R
LiO
Li
TMS
R
R
Li
H. Nakahara, 1990, 63, 3361
tBu
tBu
Me
Me
O
O
Me
O
3. DBU
66–33% in 3 steps
Convenient precursor for dienals
R
R
TMSO
THF
99-81%
TMSO
SMe
CHO
N. Yahata, 1990, 63, 3601
nBuLi
Nu
SnBu3
TolO2S
Y. Tohda, 1990, 63, 2820
Reverse Brook rearrangement
R
SO2Tol
1. nBuLi or NaH, RBr
2. HClaq
3 steps
Me
R 1 = H, alkyl, Ar, Het
R 2 = H, alkyl
TMSO
Group Meeting
9/26/15
BCSJ 5 Years Review: 1990–1986
Yuzuru Kanda
Me MAD
tBu
Al
O
O
tBu
hexane
90-60%
Less hindered, electronically labile ether selectively precipitates
K. Maruoka, 1990, 63, 3354