Download FUNCTIONAL GROUP INTERCONVERSIONS 119 Functional

FUNCTIONAL GROUP INTERCONVERSIONS
119
Functional Group Interconversions
C&S Chapter 3 #1; 2; 4a,b, e; 5a, b, d; 6a,b,c,d; 8
1
2
3
4
5
6
7
sulfonates
halides
nitriles
azides
amines
esters and lactones
amides and lactams
Sulfonate Esters
- reaction of an alcohols (1° or 2°) with a sulfonyl chloride
R OH
O
R'SO2Cl
R'=
R O S
CH3
mesylate
CF3
triflate
R'
O
sulfonate ester
CH3
- sulfonate esters are very good leaving groups.
competing side reaction
tosylate
Elimination is often a
Halides
- halides are good leaving groups with the order of reactivity in SN2 reactions
being I>Br>Cl. Halides are less reactive than sulfonate esters, however
elimination as a competing side reaction is also reduced.
- sulfonate esters can be converted to halides with the sodium halide in acetone
at reflux. Chlorides are also converted to either bromides or iodides in the same
fashion (Finkelstein Reaction).
O
R O S
R'
X-
X= Cl, Br, I
R X
O
R Cl
NaI, acetone
reflux
- conversion of hydroxyl groups to halides:
R OH
- R-OH to R-Cl
- SOCl2
- Ph3P, CCl4
- Ph3P, Cl2
- Ph3P, Cl3CCOCCl3
R
I
Organic Reactions 1983, 29, 1
R X
FUNCTIONAL GROUP INTERCONVERSIONS
- R-OH to R-Br
- PBr3, pyridine
- Ph3P, CBr4
- Ph3P, Br2
- R-OH to R-I
- Ph3P, DEAD, MeI
Nitriles
- displacement of halides or sulfonates with cyanide anion
KCN, 18-C-6
DMSO
R X
R C
N
- dehydration of amides
O
R
-
R C N
NH2
POCl3, pyridine
TsCl, pyridine
P2O5
SOCl2
- Reaction of esters and lactones with dimethylaluminium amide
TL 1979, 4907
Me
H 3C
Me2AlNH2
O
O
OH
JOC 1987, 52, 1309
NC
Ar
Ar
- Dehydration of oximes
R CHO
N
H2NOH•HCl
R
OH
P2O5
R C
H
N
- Oxidation of hydrazones
O
O
N
NMe2
(97%)
- Reduced to aldehydes with DIBAL.
DIBAL
RC≡N
C
N
RCHO
Tetrahedron Lett.
1998, 39, 2009
120
FUNCTIONAL GROUP INTERCONVERSIONS
121
Azides
- displacement of halides and sulfonates with azide anion
LDA, THF
NBS
O
O
O
NaN3
O
O
O
SO2N(C6H11)2
SO2N(C6H11)2
Br
SO2N(C6H11)2 N3
O
O
O
TL 1986, 27, 831
HO
SO2N(C6H11)2
NH2
NH2
- activation of the alcohol
R OH
+
+
N
+
N
F
Me
N
Me
+
EtO2C N N CO2Et
O
Me
TsO -
R OH
+
R N3
OR
Ph3P, NaN3
+
PPh3
EtO2C
N N
_
CO2Et
DEAD
activated alcohol
+
R O PPh3
R-OH
R N3
+
Ph3P=O
JOC 1993, 58, 5886
HO
(PhO)2P(O)-N3
O
N3
O
O
DBU, PhCH3
SN2
P(OPh)2
+
+ DBU-H
-
+ N3
(91 %)
O
(97.5 % ee)
Ar
(99.6 % ee)
- Photolyzed to aldehydes
Amines
- Gabriel Synthesis
O
N - K+
O
R
O
- reduction of nitro groups
R NO2
H2, Pd/C
Al(Hg), H2O
NaBH4
LiAlH 4
Zn, Sn or Fe and HCl
H2NNH2
sodium dithionite
X
N R
H2NNH2
O
R NH2
R NH2
FUNCTIONAL GROUP INTERCONVERSIONS
- reduction of nitriles
R C N
R CH2 NH2
H2, PtO 2/C
B2H6
NaBH4
LiAlH 4
AlH3
Li, NH3
- reduction of azides
R N3
H2, Pd/C
B2H6
NaBH4
LiAlH 4
Zn, HCl
(RO)3P
Ph3P
thiols
R NH2
- reduction of oximes (from aldehydes and ketones)
N
R
OH
NH2
R'
R
R'
R'
R
N
H2, Pd/C
Raney nickel
NaBH4, TiCl4
LiAlH 4
Na(Hg), AcOH
- reduction of amides
O
R
N
R'
R''
R''
H2, Pd/C
B2H6
NaBH4, TiCl4
LiBH4
LiAlH 4
AlH3
- Curtius rearrangement
O
O
NaN3
R
R N O
isocyanate
H2O
O
∆
- N2
R
••
N
••
Cl
••
R
••
••
N N N
+
nitrene
R NH2
122
FUNCTIONAL GROUP INTERCONVERSIONS
- reductive aminations of aldehydes and ketones
- Borsch Reaction
- Eschweiler-Clark Reaction
- alkylation of sulfonamides
Tf
Tf
N
HN
N
HN
Tf
Tf
K2CO3, DMF
110°C
Tf
Br
Br
Tf
N
N
N
N
Tf
NH HN
Na, NH3
TL 1992, 33 , 5505
NH HN
Tf
cyclam
- transaminiation
O
Ph
N
PhCH2NH2
Ph
N
NH2
Can. J. Chem.
1970, 48, 570
H3O +
tBuOK
H+
Esters and Lactones
- Reaction of alcohols with "activated acids"
- Baeyer-Villigar Reaction
Organic Reactions 1993, 43, 251
- Pd(0) catalyzed carboylation of enol triflates
OTf
CO2R
CO, DMF
Pd(0), ROH
TL 1985, 26 , 1109
- Arndt-Eistert Reaction
O
R
Angew. Chem. Int. Ed. Engl. 1975, 15, 32.
O
CH2 N2
Cl
Et2 O
O
hν
N2
R
Wolff
Rearrangement
C O
H
O
R'OH
R
OR'
ketene
O
O
TsN3, Et3N
CO2Me
R
••
CH
R
ROH
R
diazo ketone
N2
R
- Diazoalkanes: carbene precursors
R-CHO
1) NH2NH2
2) Pb(OAc)4, DMF
R-N2
R3N
H 2N
R
- Halo Lactonizations
JOC 1995, 60, 4725
TsN3
N
N2
R
R
review: Tetrahedron 1990, 46 , 3321
+
I
I
I2-KI
CO2H
R
H2O, NaHCO3
O
O
H
O
O
123
FUNCTIONAL GROUP INTERCONVERSIONS
Pd(OAc)2
(5 mol %)
CO2H
JOC 1993, 58, 5298
O
DMSO, air
(86%)
O
- Selenolactonization
PhSe
O
H 2O 2
O
PhSeCl, CH2Cl2
O
O
JACS 1985,
107 , 1148
O
OH
- Mitsunobu Reaction
Synthesis 1981 , 1; Organic Reactions, 1991, 42, 335
Mechanism: JACS 1988, 110 , 6487
O
DEAD, Ph3P
OH
R
O
R''CO2H
R'
R
R''
Inversion of alcohol
stereochemistry
R'
Amides and Lactams
- reaction of an "activated acid" with amines
- Beckman Rearrangement
Organic Reactions 1988, 35, 1
O
R
N
R'
R
OH
PCl5
O
R'
R
NR'
- Schmidt rearrangement
O
R
O
HN3
R'
H+
R
NR'
- others
O
OTf
NR2
CO, DMF
Pd(0), R2NH
TL 1985, 26 , 1109
OH
O
O
O
PhCH2NH2
N
H
AlMe3
OTHP
Ph
TL 1977, 4171
OTHP
-Weinreb amide Tetrahedron Lett. 1981, 22, 3815
O
DIBAL
O
R
O
H3CNH(OCH3) •HCl
OR'
AlMe3
R
R
N
H
OCH3
O
CH3
R1-M
R
R1
124