FUNCTIONAL GROUP INTERCONVERSIONS 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

119

Sulfonate Esters - reaction of an alcohols (1 or 2) with a sulfonyl chloride

R OH R'SO2Cl O R O S O sulfonate ester R' CF3 CH3 triflate tosylate R'= CH3 mesylate

- sulfonate esters are very good leaving groups. competing side reaction

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 O
NaI, acetone reflux

R'

X-

R X

X= Cl, Br, I

R Cl

- conversion of hydroxyl groups to halides:

R OH

Organic Reactions 1983, 29, 1

R X

- R-OH to R-Cl - SOCl2 - Ph3P, CCl4 - Ph3P, Cl2 - Ph3P, Cl3CCOCCl3

FUNCTIONAL GROUP INTERCONVERSIONS

120

- 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
R X KCN, 18-C-6 DMSO R C N

- dehydration of amides
O R NH2 R C N

POCl3, pyridine TsCl, pyridine P2O5 SOCl2

- Reaction of esters and lactones with dimethylaluminium amide TL 1979, 4907

Me Me2AlNH2 O O Ar H 3C NC Ar OH JOC 1987, 52, 1309

- Dehydration of oximes
R CHO H2NOHHCl R N OH P2O5 H R C N

- Oxidation of hydrazones
O O N NMe2 (97%) C N Tetrahedron Lett. 1998, 39 , 2009

- Reduced to aldehydes with DIBAL. DIBAL

RCN

RCHO

FUNCTIONAL GROUP INTERCONVERSIONS Azides - displacement of halides and sulfonates with azide anion
O O SO2N(C6H11)2 O O SO2N(C6H11)2 NH2 HO NH2 LDA, THF NBS O SO2N(C6H11)2 Br O NaN3 O SO2N(C6H11)2 N3 O TL 1986, 27, 831 O

121

- activation of the alcohol

R OH + + N Me TsO Ph3P, NaN3 EtO2C

+ N Me

R N3 OR

+ N Me O

+ PPh3 N N _ CO2Et

R OH

EtO2C N N CO2Et DEAD + R O PPh3

activated alcohol R-OH R N3 + Ph3P=O

N3 SN2 + DBU-H
+

JOC 1993, 58, 5886

HO (PhO)2P(O)-N3 O DBU, PhCH3 (99.6 % ee) Ar O O P(OPh)2 + N3
-

(91 %)

O (97.5 % ee)

- Photolyzed to aldehydes Amines - Gabriel Synthesis

O N - K+ O R X O N R O H2NNH2 R NH2

- reduction of nitro groups R NO2 H2, Pd/C Al(Hg), H2O NaBH4 LiAlH 4 Zn, Sn or Fe and HCl H2NNH2 sodium dithionite

R NH2

FUNCTIONAL GROUP INTERCONVERSIONS - reduction of nitriles R C N 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
OH NH2 R' R R'

122

R CH2 NH2

R NH2

- reduction of oximes (from aldehydes and ketones)

N R

H2, Pd/C Raney nickel NaBH4, TiCl4 LiAlH 4 Na(Hg), AcOH - reduction of amides
O R N R'' R' R N R'' R'

H2, Pd/C B2H6 NaBH4, TiCl4 LiBH4 LiAlH 4 AlH3 - Curtius rearrangement
O NaN3 R Cl R O
N N N +

- N2 R NH2 R

O
N

nitrene

R N O isocyanate

H2O

FUNCTIONAL GROUP INTERCONVERSIONS - reductive aminations of aldehydes and ketones - Borsch Reaction - Eschweiler-Clark Reaction - alkylation of sulfonamides
Tf N N HN HN Tf Tf Br Br Tf K2CO3, DMF 110C Tf N N N N Tf Na, NH3 Tf NH HN NH HN cyclam

123

TL 1992, 33 , 5505

Tf

- transaminiation
O PhCH2NH2 H+ N Ph tBuOK N Ph H3O + NH2

Can. J. Chem. 1970, 48, 570

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 CO, DMF Pd(0), ROH CO2R TL 1985, 26 , 1109

- Arndt-Eistert Reaction
O R Cl CH2 N2 Et2 O R

Angew. Chem. Int. Ed. Engl. 1975, 15, 32.

O R diazo ketone C O H ketene N2 h ROH R O

CH
O

Wolff Rearrangement

R'OH

OR'

O R CO2Me

TsN3, Et3N R

O N2

- Diazoalkanes: carbene precursors

R-CHO 1) NH2NH2 2) Pb(OAc)4, DMF R3N
H 2N R N R

R-N2
TsN3 R

JOC 1995, 60, 4725

N2 R

- Halo Lactonizations
CO2H

review: Tetrahedron 1990, 46 , 3321

+ I2-KI H2O, NaHCO3 O H O O I I O

FUNCTIONAL GROUP INTERCONVERSIONS

Pd(OAc)2 (5 mol %) CO2H DMSO, air (86%) O O

124

JOC 1993, 58, 5298

- Selenolactonization
PhSe O OH PhSeCl, CH2Cl2 O O H 2O 2 O O JACS 1985, 107 , 1148

- Mitsunobu Reaction

Synthesis 1981 , 1; Organic Reactions, 1991, 42, 335 Mechanism: JACS 1988, 110 , 6487
O DEAD, Ph3P R''CO2H R O R' R'' Inversion of alcohol stereochemistry

OH R R'

Amides and Lactams - reaction of an "activated acid" with amines - Beckman Rearrangement Organic Reactions 1988, 35, 1
O R R' R
O R R'

OH R'

PCl5 R
O R NR'

O NR'

- Schmidt rearrangement
HN3 H+

- others
O OTf CO, DMF Pd(0), R2NH NR2 TL 1985, 26 , 1109

O O PhCH2NH2 AlMe3 OTHP

OH O N H OTHP Ph TL 1977, 4171

-Weinreb amide Tetrahedron Lett. 1981, 22, 3815

DIBAL O R OR' H3CNH(OCH3) HCl AlMe3 R O N OCH3 O R1-M R R1 R CH3 O H