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(1). RCH2NH2
C-H
p-TsCl BuLi LiAlH4 RCH2-H
ArSO2Cl RCH2NH2 Hinsberg's test
O
RCH2NH
SO2Ar
BuLi - BuH N SO2Ar
RCH2N SO2Ar
tosylamide RCH2
(2).
Ar-NH2
p-TsCl
NaH NH2Cl
NaH
p-TsCl Ar-H
CH3
S Cl O
LiAlH4 RCH2-H SO2Ar tosylimide weaker C-N bond N NH Ar N N Ar-H
(3). Ar-NH2
NaNO2 H3PO2 HCl
via:
Ar-H
Ar
N
NaH NH2 - ArSO H 2
SO2Ar
Ar
JOC, 2001, 66, 8293.
C-CH3 9- a C-X
d e
C
C
-C(O)-CH3
CRR'=CHX
f C=O g C C h C CH i C=C j C-OH
C-H 1- a b c d C-OH C-X C-NH2 C-S e C=O f C=C g C-CN h C-CO2H i j C-CHO C(O)X
J. Org. Chem. 2000, 65, 6179
LiAlH4 RCH2-H Ph via: H Cl2In Cl O
RCH2 O S CH3 O O RCH2 O S CF3 O Ph H SiPh2 InCl3
i. p-TsCl // LiAlH4
RCH2OH
dry Py Ph Ph2SiHCl / InCl3 CHCl2 rt, 3 hr JOC, 2001, 66, 7741. Ph Ph
H
CO2Me RhCl(PPh3)3 benzene 12 hr O O
CO2Me
O
JACS, 1979, 101, 7020.
via:
H
CH3CO2D
B R R
D prepare isotope
N2H2: unstable; generated in situ from "DEAD" (diethyl azodicarboxylate) or from: N2H4 + H2O2; N2H4 + Cu(II) + O2; NH2OH + NH2OSO3 EtO2C N N CO2Et OH-
Synthesis, 2001, 16, 2370. N N Ts H-
H H for acyclic, may C=C side product
O
(6). enol derivatives:
Tf2O /
N
// H2 / PtO2
limit: for -H compd.
RED choice: MeLi; NaBH3CN (good) LAH, NaBH4: 2 group compete at Stanford U. B2H6: very flamable, fire if shoot out from syringe Ph H O C C
iii NaBH3CN
NaBH3CN: stable at pH 5-6 JOC, 1976, 41, 3064. Br
iv LiBHEt3 (super hydride)
(3). metal reduction
i Na / NH3; Li / NH3; Na / EtOH ii Zn; Fe; Sn; Mg
Functional Group Interconversion
C-H 1- a b c d e f g h i j C C 6- a b c d e f g h i RC CH RCH2-SO2Ph C C C=C RCH(CO2H)-CH3 -C(O)-CH3
O X O O
C-OR C-OH C-X C-NH2 C-S C=O C=C C-CN C-CO2H C-CHO C(O)X C=C 7- a CH-CX b CH-CH c CX-CY
(4). RCH2NH2
RCH2NMe3 X
-
Ag2O
RCH2NMe3 OH-
R=CH2
R-CH3
1-d
C-S
C-H
radical mechanism
EtO2C HN MeO2C S N O
JOC, 1985, 50, 427.
EtO2C CH2Ph
Raney Nickel: Ni - Al alloy, suspension
O N2H4
N NH2
OH-
NN H
H
OHN N H - N2
H
H
N N
(4). Pd-C / HCO2NH4: mild, efficient
major side-product: drawback of the reaction
Ph
(5). Tosylhydrazone reduction (Shapiro reaction): (modified Wolff-Kishner reduction):) TsNHNH2 // RED
Mg / Et2O
H2O
H (Grignard reagent) Br
N CN
N - N2 CN
n-BuSnH
R n-BuSn n-BuSnBr
H R n-BuSnH n-BuSn R
CN (AIBN) azobisisobutyronitrile radical initiator
1-c C-NH2
(1). free radical reduction
i n-Bu3SnH / AlBN ii NaBH4 / InCl3 / CH 3CN
JACS, 2002, 124, 906.
radical reagent
i LiAlH4 (2). hydride reduction ii NaBH4
JACS, 1972, 94, 8905. JOC, 1969, 34, 3923. THL, 1969, 3095. hygroscopic, dried self, suggest: buy small amount each time unstable in acid, form H2 gas; stable in weak base
S C O Ph n-Bu3SnH CH 3
CH3 H CH3
via:
S O C O Ph
SnBu3 S O C O Ph
thiocarbonate
(an ester) steric OK
1-bΒιβλιοθήκη Baidu
C-X
C-H
Br n-Bu3SnH AIBN H Bu3SnH: (l), easy to remove Ph3SnH: (s), hard to remove Me3SnH: too volatile, toxic
1-a C-OH
(1). for 1', 2' alcohol:
C-H
O CH3 S Cl O
O RCH2 O S O O CH3 tosylate mesylate triflate toluenesulfonyl chloride (s) ~ $ 30 / Kg methanesulfonyy chloride (l) ~ $ 30 / Kg purification textbook dry pyridine: from CaH2 and distilled
O CF3 S O O O S CF3 O
B H
O
O (7). Et3SiH / CF3COOH NO2 Ph Et3SiH CF3COOH JOC, 1973, 38, 2675. NO2
C C
OTf
H2 PtO2
H H C C H
N
PtO2 + H2 = Pt
1-f
C=C
C-C-H
H2 PtO2 HO HO H H OH OH stereoselcetive: same side as OH (due to H bond) N H2 , PtO2 TFA , 60 ℃ in acetic condition JOC, 2002, 67, 7890.
X
C-OH 3- a b c d e f g h i j C-H C-OR C-X C-NH2 C-OCH2OR C-OC(O)R C---OH C=O C O C=C C-X 8- a C-OH b C-NH2 c C=O d C(O)Z e C-H
C-N 4- a b c d e f g h C-H C-N C-X C-OH C=O C=C C-C(O)Z C N
C=O 5- a b c d e f g h i j k C=O C=S C=N-OH, C=N-H C C C N C=C-OR; C=C-SR C(OR)2; C(SR)2 C-OH C-NH2; C-NO2 C-Br C-H
2- a C-OH b C-(OR)2 c C(O)OR d C-H e C=C f C-CN
O
SH S H S thioketal
Ra(Ni)
H H
BF3, CH2Cl2
H
(1). Clemmensen reduction: Zn-Hg / HCl similar: Sn / HCl (2). thioketal: SH SH / BF3, CH2Cl2 // RaNi N2H4, OH-, heat
JCS, PT1, 1986, 546.
R
R C C R
HO2C N N CO2H O H H O N N O O
H N N H - 2 CO2
R
R R C C H H
R R
- N2
syn-addition
OEt O
OEt n-Bu2SnI MgBr2-Et2O JOC, 2001, 66, 8690. H3O+ O OEt via: I Sn H R O R
(1). H2 / cat
catalyst: Pd-C PtO2 Rh-C; Rh-Al2O3; RhCl(PPh3)3 Ni
R
R N R = NHAc , NH2
(2). HN=NH (diimide) JOC, 1993, 58, 4979. (3). B2H6 // RCO2H, heat (4). n-Bu2SnI / MgBr2-Et2O // H3O+ O RhCl(PPh3)3 O O Wilkinson's catalyst: regioselective, prefer isolated double bond soluble in org solvent, 9 Ph group $ 50 / 25 g
I
OEt not radical mech. O Sn R
H R
1-g C C N
C-H
CN: ~ X (pseudo halogen), form KCN, NaCN with IA elements
(1). K / Al2O3 JOC, 1980, 45, 3227 K / HMPA (2). Na / NH3
acidic
C6H13
thioketal: inert to LAH; react with RaNi; smell terrible and stay long; discard shoses
neutral basic O Pd-C Ph HCO2NH4 Ph Ph
(3). Wolff-Kishner reduction:
HN MeO2C H N CH2Ph
(1). Raney Ni (2). Li / NH3
Raney Ni
burn filter paper if dry mechanism uncertain, probably radical
(3). LiAlH4 / CuCl2 JCS Perkin Trans I, 1973, 654. NaBH4 / NiCl2 NaBHEt3 / FeCl2 (or CoCl2, VCl3)
ii. Ph2SiHCl / InCl3
Ph
OH
indium trichloride a unique Lewis acid catalyst, acceleratedeoxgyenation
(2). for 3' alcohol: CH3 i. ClC(S)OPh // n-Bu3SnH ii. Et3SiH / Lewis acid CH3 OH CH3 JOC, 2000, 65, 6179. Cl
Chemistry:
R-SH R-S-R R-SS-R remove: Hg+; Ni
R2SO R2SO2
1-e
C=O
C-H
HS best suitable for aryl ketone (ArCOR); not good for conjugate ketone OH O preparation: HgCl2 into Zn
C-H
p-TsCl BuLi LiAlH4 RCH2-H
ArSO2Cl RCH2NH2 Hinsberg's test
O
RCH2NH
SO2Ar
BuLi - BuH N SO2Ar
RCH2N SO2Ar
tosylamide RCH2
(2).
Ar-NH2
p-TsCl
NaH NH2Cl
NaH
p-TsCl Ar-H
CH3
S Cl O
LiAlH4 RCH2-H SO2Ar tosylimide weaker C-N bond N NH Ar N N Ar-H
(3). Ar-NH2
NaNO2 H3PO2 HCl
via:
Ar-H
Ar
N
NaH NH2 - ArSO H 2
SO2Ar
Ar
JOC, 2001, 66, 8293.
C-CH3 9- a C-X
d e
C
C
-C(O)-CH3
CRR'=CHX
f C=O g C C h C CH i C=C j C-OH
C-H 1- a b c d C-OH C-X C-NH2 C-S e C=O f C=C g C-CN h C-CO2H i j C-CHO C(O)X
J. Org. Chem. 2000, 65, 6179
LiAlH4 RCH2-H Ph via: H Cl2In Cl O
RCH2 O S CH3 O O RCH2 O S CF3 O Ph H SiPh2 InCl3
i. p-TsCl // LiAlH4
RCH2OH
dry Py Ph Ph2SiHCl / InCl3 CHCl2 rt, 3 hr JOC, 2001, 66, 7741. Ph Ph
H
CO2Me RhCl(PPh3)3 benzene 12 hr O O
CO2Me
O
JACS, 1979, 101, 7020.
via:
H
CH3CO2D
B R R
D prepare isotope
N2H2: unstable; generated in situ from "DEAD" (diethyl azodicarboxylate) or from: N2H4 + H2O2; N2H4 + Cu(II) + O2; NH2OH + NH2OSO3 EtO2C N N CO2Et OH-
Synthesis, 2001, 16, 2370. N N Ts H-
H H for acyclic, may C=C side product
O
(6). enol derivatives:
Tf2O /
N
// H2 / PtO2
limit: for -H compd.
RED choice: MeLi; NaBH3CN (good) LAH, NaBH4: 2 group compete at Stanford U. B2H6: very flamable, fire if shoot out from syringe Ph H O C C
iii NaBH3CN
NaBH3CN: stable at pH 5-6 JOC, 1976, 41, 3064. Br
iv LiBHEt3 (super hydride)
(3). metal reduction
i Na / NH3; Li / NH3; Na / EtOH ii Zn; Fe; Sn; Mg
Functional Group Interconversion
C-H 1- a b c d e f g h i j C C 6- a b c d e f g h i RC CH RCH2-SO2Ph C C C=C RCH(CO2H)-CH3 -C(O)-CH3
O X O O
C-OR C-OH C-X C-NH2 C-S C=O C=C C-CN C-CO2H C-CHO C(O)X C=C 7- a CH-CX b CH-CH c CX-CY
(4). RCH2NH2
RCH2NMe3 X
-
Ag2O
RCH2NMe3 OH-
R=CH2
R-CH3
1-d
C-S
C-H
radical mechanism
EtO2C HN MeO2C S N O
JOC, 1985, 50, 427.
EtO2C CH2Ph
Raney Nickel: Ni - Al alloy, suspension
O N2H4
N NH2
OH-
NN H
H
OHN N H - N2
H
H
N N
(4). Pd-C / HCO2NH4: mild, efficient
major side-product: drawback of the reaction
Ph
(5). Tosylhydrazone reduction (Shapiro reaction): (modified Wolff-Kishner reduction):) TsNHNH2 // RED
Mg / Et2O
H2O
H (Grignard reagent) Br
N CN
N - N2 CN
n-BuSnH
R n-BuSn n-BuSnBr
H R n-BuSnH n-BuSn R
CN (AIBN) azobisisobutyronitrile radical initiator
1-c C-NH2
(1). free radical reduction
i n-Bu3SnH / AlBN ii NaBH4 / InCl3 / CH 3CN
JACS, 2002, 124, 906.
radical reagent
i LiAlH4 (2). hydride reduction ii NaBH4
JACS, 1972, 94, 8905. JOC, 1969, 34, 3923. THL, 1969, 3095. hygroscopic, dried self, suggest: buy small amount each time unstable in acid, form H2 gas; stable in weak base
S C O Ph n-Bu3SnH CH 3
CH3 H CH3
via:
S O C O Ph
SnBu3 S O C O Ph
thiocarbonate
(an ester) steric OK
1-bΒιβλιοθήκη Baidu
C-X
C-H
Br n-Bu3SnH AIBN H Bu3SnH: (l), easy to remove Ph3SnH: (s), hard to remove Me3SnH: too volatile, toxic
1-a C-OH
(1). for 1', 2' alcohol:
C-H
O CH3 S Cl O
O RCH2 O S O O CH3 tosylate mesylate triflate toluenesulfonyl chloride (s) ~ $ 30 / Kg methanesulfonyy chloride (l) ~ $ 30 / Kg purification textbook dry pyridine: from CaH2 and distilled
O CF3 S O O O S CF3 O
B H
O
O (7). Et3SiH / CF3COOH NO2 Ph Et3SiH CF3COOH JOC, 1973, 38, 2675. NO2
C C
OTf
H2 PtO2
H H C C H
N
PtO2 + H2 = Pt
1-f
C=C
C-C-H
H2 PtO2 HO HO H H OH OH stereoselcetive: same side as OH (due to H bond) N H2 , PtO2 TFA , 60 ℃ in acetic condition JOC, 2002, 67, 7890.
X
C-OH 3- a b c d e f g h i j C-H C-OR C-X C-NH2 C-OCH2OR C-OC(O)R C---OH C=O C O C=C C-X 8- a C-OH b C-NH2 c C=O d C(O)Z e C-H
C-N 4- a b c d e f g h C-H C-N C-X C-OH C=O C=C C-C(O)Z C N
C=O 5- a b c d e f g h i j k C=O C=S C=N-OH, C=N-H C C C N C=C-OR; C=C-SR C(OR)2; C(SR)2 C-OH C-NH2; C-NO2 C-Br C-H
2- a C-OH b C-(OR)2 c C(O)OR d C-H e C=C f C-CN
O
SH S H S thioketal
Ra(Ni)
H H
BF3, CH2Cl2
H
(1). Clemmensen reduction: Zn-Hg / HCl similar: Sn / HCl (2). thioketal: SH SH / BF3, CH2Cl2 // RaNi N2H4, OH-, heat
JCS, PT1, 1986, 546.
R
R C C R
HO2C N N CO2H O H H O N N O O
H N N H - 2 CO2
R
R R C C H H
R R
- N2
syn-addition
OEt O
OEt n-Bu2SnI MgBr2-Et2O JOC, 2001, 66, 8690. H3O+ O OEt via: I Sn H R O R
(1). H2 / cat
catalyst: Pd-C PtO2 Rh-C; Rh-Al2O3; RhCl(PPh3)3 Ni
R
R N R = NHAc , NH2
(2). HN=NH (diimide) JOC, 1993, 58, 4979. (3). B2H6 // RCO2H, heat (4). n-Bu2SnI / MgBr2-Et2O // H3O+ O RhCl(PPh3)3 O O Wilkinson's catalyst: regioselective, prefer isolated double bond soluble in org solvent, 9 Ph group $ 50 / 25 g
I
OEt not radical mech. O Sn R
H R
1-g C C N
C-H
CN: ~ X (pseudo halogen), form KCN, NaCN with IA elements
(1). K / Al2O3 JOC, 1980, 45, 3227 K / HMPA (2). Na / NH3
acidic
C6H13
thioketal: inert to LAH; react with RaNi; smell terrible and stay long; discard shoses
neutral basic O Pd-C Ph HCO2NH4 Ph Ph
(3). Wolff-Kishner reduction:
HN MeO2C H N CH2Ph
(1). Raney Ni (2). Li / NH3
Raney Ni
burn filter paper if dry mechanism uncertain, probably radical
(3). LiAlH4 / CuCl2 JCS Perkin Trans I, 1973, 654. NaBH4 / NiCl2 NaBHEt3 / FeCl2 (or CoCl2, VCl3)
ii. Ph2SiHCl / InCl3
Ph
OH
indium trichloride a unique Lewis acid catalyst, acceleratedeoxgyenation
(2). for 3' alcohol: CH3 i. ClC(S)OPh // n-Bu3SnH ii. Et3SiH / Lewis acid CH3 OH CH3 JOC, 2000, 65, 6179. Cl
Chemistry:
R-SH R-S-R R-SS-R remove: Hg+; Ni
R2SO R2SO2
1-e
C=O
C-H
HS best suitable for aryl ketone (ArCOR); not good for conjugate ketone OH O preparation: HgCl2 into Zn