E. J.

Corey: B-Sides

Baran Group Meeting

OTBS

iPr

OTf
CsF, PhNTf2

nBu

Me

NNMe2

nBu

JACS, 2002, 124, 11290

Me

SMe

THF:H2O, 1h,
100%
NOH

O
tBu

TL, 1976, 17, 3667

ii. Cr(OAc)2,
THF:H2O,
65 C, 16h, 88%

Br

Ph

Br

C6H6, TsOH
87%

Br
Br i. BzCl, py

O
3

OTBS

CHO
3

OH

OTMS
TMSCl, LOBA

nBu

Alloc-O

nBu

OSO2F
Me
S

O
S

OtBu
OC6H4-p-OMe

5:1 (-100 C)
tBu
Tr
N
Li
TL, 2000, 41, 2515

TrN
Li

tBu

Me

R
MeOH, rt,
2h, 73%

Ph
i. TMSCl, LiBr
ii. Pd(OAc)2, BQ
91% ee

TL, 2000, 41, 6941

JOC, 1973, 38, 3223

Me

R R

OTMS

HO

Ni(CO)4, 92%

TL, 1984, 25, 495

JOC, 1992, 57, 1028

iPr

Me

S
Me

n-C5H11

(LDA then TMSCl: 85:15)

(TMSCl then LDA: 90:10

97:3
Me

OH

DIBAL, 23 C

iPr

TL, 1976, 17, 4577

For brormomethylethylene ketals: JOC, 1973, 38, 834
O

RCO2H
TL, 1977, 18, 2081

95%

OBz

ii. Zn-Ag
THF, 84%

Me
JOC, 1973, 28, 3224
For 5-methylene-1,3-dioxanes: TL, 1975, 16, 3775

ii. KSCN

n-C5H11

OH

HO

i. Hg(OAc)2, MeOH
O

JACS, 1970, 92, 5276

OH

i. Ac2O

OH

ii. pH 2 brine
93%

SMe

Cu(OAc)2

tBu

iPr

i. RhCl(PPh3)3
EtOH(aq), !

DME, 23 C, 78%
Me

Tim Newhouse

R R
MeOH, rt,
18h, 87%

MeS
S

OMe

R R

MeO

OMe

R R
TL, 1975, 16, 3267

E. J. Corey: B-Sides

Baran Group Meeting

SiF4 (commercial gas)

Tim Newhouse

OH
OTBS

OTBS

OTBS

Me
Me

Me

2h, rt, 81%

Ph

OTBS

OH

IBX, DMSO

Me
H

HO

TL, 1995, 36, 3485

tBu
tBu
DCM, rt, 1 atm:
24h: 100% SM - 15h : 94% alcohol - 93% SM, 4% alcohol - 24h: 100% SM

TL, 1992, 33, 2289

NH2
H
i. SiF4, iPr2NEt, H2O,
Et2O, 0 C, 40m, 82%
ii. DMSO, TFAA;
Et3N, 92%
iii. CBS, 80%
O

tBu

tBu

H
HO

O
tBu

92% ee

MeOH, rt

tBu

TL, 1992, 33, 2319

JACS, 1993, 115, 8873

1! O
g 2

KO2 + H2O

C(NO2)4, DMSO

Biochem. and Biophys. Res. Comm. 1987, 145, 842

and references therein
RCH2OH

i. PDC
ii. Ac2O, tBuOH

NO2

RN3

ii. O3

tBu

NH2
OH

R2CO

oxalic acid
H2O

tBu

OH
JACS, 1969, 91, 1429

tBu

RCO2tBu

JOC, 1984, 49, 4735

i. PPh3

R
tBu

HN

Recall 1!gO2 generation:

JACS, 1964, 86, 3879 + 3881
JACS, 1986, 108, 2472
Recall: epoxide deoxygenation
JACS, 1987, 109, 7534

NCHR

R2CHNH2

H
N

SnMe3

ii. H2, Pt/C

88%

JOC, 1985, 50, 5391

JACS, 1962, 84, 685

H
N
H H
pKa = 4.7 (EtOH/H2O)

i. TiCl4, 60%

Me
Br
Br

RNO2

JACS, 1984, 106, 3682

Ni(CO)4, CO
E

NMP, 50 C

CO2Me
Me

TL, 1969, 10, 1779 + JACS, 1967, 89, 2757 + 2758

For mechanism, see: JACS, 1968, 90, 2416

E. J. Corey: B-Sides

Baran Group Meeting

OLi

tBu

tBu

OMe

CO2H

CO2 (1 atm)

tBu

"Thallium and its compounds

are highly toxic and must be
handled with great care."

i. Tl2SO4, KOH

rt, 16 h, 89%

Me

Tim Newhouse

ii. Cl
OMe
-20 C, 5h, 1 mol

tBu

+ TlCl
JACS, 1971, 93, 1489

JOC, 1973, 38, 4086

O

NBA
SnCl4 or BF3Et2O

OH

EtOCHO, NaH

NHAc

MeCN, H2O, -40 C

Br

EtOH, 5h, rt 95%

tBu

JACS, 2006, 128, 6310 + 9644

tBu

JOC, 1971, 36, 3070

H3C

OOH
Me

Me

Me

Me

pTsCl, py
5-10%

JACS, 1958, 80, 6686

i. py-SO3, 0 C
OH

ii. LAH, rt, 3 h

JOC, 1969, 34, 3667

Ph

O
i. PhSCH2- Cu+, 76%
Br

i.

P Cl
, py

RI +

ii. I2

ArO2SN

TsCl, py

NSO2Ar

O
I

O
RNC
JACS, 1958, 80, 2903

O2N

HO

2 days
50:1 dr, 100%

97% ee

Ph
Ph

Method development:
Applications:

JACS, 1991, 113, 4026

JACS, 1995, 117, 193
JACS, 1996, 118, 1229
For enantioselective syn and anti aldol reactions
with chiral boron enolates, see:
JACS, 1990, 112, 4976
SO2NHNH2

Me O

4 C

Ph

Ph

B
Br

O
Ph

P
JOC, 1967, 32, 4160

RNHCHO

Ph

TL, 1968, 5787

JACS, 1968, 90, 5618

2NEt

-78 C

O
O

ROH

iPr

Ph

ii. MeI, NaI, DMF

CaCO3, Hg, 58%

*
OBR2

Me O

NO2

base, 2h
0 C ! rt, 62%

O
OHC

JOC, 1975, 40, 579

E. J. Corey: B-Sides

Baran Group Meeting

i.
C5H11

Ph
Ph
A=
H OH
Ph
A, -78 C, 2h
DCM
NSO2Tol
TolO2SN
C5H11
B
H OMOM 80%, dr = 25:1
H OMOM
allyl
opposite ent: dr = 39:1
up to 99% ee for allylations
JACS, 1989, 111, 5495
SnBu3
JACS, 1981, 103, 4618
H OH
H OH
or
or
R-CHO
R
R
S
nBuLi
SnPh
Ph

Li - en
HMPA:THF,
-20 C, 12h

ii. TBSCl, imid.

94%

TBSO

S
S

S
BF4

0-25 C, 96%

CHO

96%

JACS, 1990, 112, 878

For alkynylation with oxazaborolidines: JACS, 1994, 116, 3151

S
OH

200 C, 4h
97%

94%

ii. TsOH, 55%

Me

Me

H
HO

OH
BnO

OBn

O
Et2Zn

JACS, 2001, 123, 4475

Zn
Ar Et

JOC, 1976, 41, 260

CO2Me

Me

OH

Zn/TMSCl
2,6-lutidine, THF
77%

CO2Me

C6H5
Et

OH

OH

Me
Me N
N
Me
Li

CpTiCl3 - LAH: 55%

Me
Me

OH

OH

0 C, 30 min
93%

NaCNBH3, 91%

NH2

TL, 1978, 19, 2461

HCl, NaNO2,
THF, 0 C;

PhCHO

i. PCC

Mg(Hg)-TiCl4

OBn

Me

HgCl2, CaCO3

JACS, 1972, 94, 8932

Me

Tim Newhouse

HO

Et
90% ee

H
TL, 1987, 28, 5233
Alternate catalyst and mechanistic studies: JOC, 1990, 55, 784
Ph

C3H7-CO2Me

nC H -Br
4 9
Mg, ClTi(OiPr)

rt, 79%

C2H5

HO
3

C3H7
single diastereomer

TL, 1983, 24, 2821

E. J. Corey: B-Sides

Baran Group Meeting

Br

CO2Et
Me
Me
O

CH2

O
S

OEt

OEt

i. THF, !

CO2Me

ii. h", MeOH,

80%

SOMe

Me
LiCuMe2

JACS, 1964, 86, 1640

0 C, 2.5h, 81%

sBuLi

JACS, 1967, 89, 3911

JACS, 1968, 90, 5615
For examination of other metals: TL, 1970, 11, 315

-78 - 50 C
CHO
JACS, 1970, 92, 5522

then HgO 190 C

Me

Me
Br

0 C, 68%

tBu

0 C, 85%

CuCH2CN

Pd(OAc)2, TBHP
K2CO3

Pd/C, TBHP
K2CO3
tBu

Tim Newhouse

CN

-20 C, 1h, 92%

tBu

OOtBu

Me

Me

Me

Me
TL, 1972, 13, 487

OL, 2002, 4, 2727

For dieneones from enones: JACS, 2003, 125, 3232
OH

OH

Me

CH2I2, Zn-Cu

NHTrisyl

CHO
350 C

Me

90%

H
Me

Me
JACS, 1970, 92, 6636

O
O

TMS

O
O(nBu4N)

I
OBn

82%

O Ph3P Me
tBuLi,

i.
-40 C
ii. 0 C - rt, 20 h

54%

TL, 1997, 38, 8915

JACS, 1985, 107, 256

OH
PhCHO

TL, 1972, 13, 111

O

O
PPh3

TsO
Br

O(nBu4N)
OBn

TMS

iii. TMEDA, nBuLi

-78 - 0 C, 30 min
iv. Li(2-Thienyl)CuCN
-78 C, 15 min
v. B, -78 - 0 C

Me

64%

Me

i. nBuLi, DME, -78

to -60 C, 20 min
ii. A, -65 C, 10-18h

O
JACS, 1982, 104, 4725

OTBS

vinyl-Li, -78 C

Ph

-78C - rt, 65%

TBS
then I2, 2h
74%

2
JACS, 2002, 124, 11290

E. J. Corey: B-Sides

Baran Group Meeting

O

BF3K

Me

O
Ph

EtLi, CuI

OH

Me

90%, 92% ee

N
Me

NMe2

Me
[Rh(cod)2]BF4, BINAP
PhMe, Et3N, rt, 3 days
87%, >98% ee

JACS, 1986, 108, 7114

O

Tim Newhouse

TL, 2008, 49, 4894

For synthesis of platensimycin: OL, 2007, 9, 4921

O
Ni(CO)4, BuLi
-50 C, 12h, 64%

ArOCH2Cl + LiSnBrCl2

O
Bu

"
O

i.
Bu3Sn

ArOCH2SnBrCl2

i. sBuLi / KOtBu
ii. CuBr

OtBu

ii. Pb(OAc)4, 96%

JACS, 1974, 96, 5581

For development of mixed cuprates, see: JACS, 1972, 94, 7210

ArOCH2Li + Bu4Sn

O
tBuOMe

4 eq BuLi

TL, 1983, 24, 3163

JACS, 1969, 91, 4926

"
CuCCPh
Li

THF

THPO O

THPO

CuLi

O
O

37%

CO2Me

TL, 1983, 24, 3165

CO2Me
JACS, 1972, 94, 4014

"

Ar2
P
NiCl2
P
Ar2

CHO

LDA, 5h, -75 C

O

MeS

iBu

Ph
2Al
PhMe, -45 C,
74%, 85% ee

OH

OMe

OH
SMe

SMe

Ar = m-terphenyl

Me Me

"

82%

SMe

CHO

JACS, 1971, 93, 1724

Me Me

Ph

OL, 2010, 12, 300

For another system: OL, 2004, 6, 3385

Also effects conjugate reductions with DIBAH, see also:

Mg/MeOH - JOC, 1975, 40, 127
H2S then PPh3/hv - JACS, 1983, 105, 1662

OMe
Me
Si
Me

MeO
Me
Si
Me

OMe
Me
MeLi, THF:HMPA

Si

-50 C, 5h

Me

Li

JACS, 2001, 123, 1872

OL, 2001, 3, 333