Functional Group Interconversions 119

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Functional Group Interconversions

C&S Chapter 3 #1; 2; 4a,b, e; 5a, b, d; 6a,b,c,d; 8

1 sulfonates 2 halides 3 nitriles 4 azides 5 amines 6 esters and lactones 7 amides and lactams

Sulfonate Esters - reaction of an alcohols (1° or 2°) with a sulfonyl chloride O R'= R'SO2Cl CH3 mesylate R OH R O S R' triflate O CF3 sulfonate ester CH3 tosylate

- sulfonate esters are very good leaving groups. Elimination is often a competing side reaction

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 X- R O S R' R X X= Cl, Br, I O

NaI, acetone reflux R Cl R I

- conversion of hydroxyl groups to halides: Organic Reactions 1983, 29, 1 R OH 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 KCN, 18-C-6 DMSO R X R C N - dehydration of amides O R C N R NH2 - POCl3, pyridine - TsCl, pyridine - P2O5 - SOCl2

- Reaction of esters and lactones with dimethylaluminium amide TL 1979, 4907 Me H3C Me2AlNH2 OH JOC 1987, 52, 1309 O NC Ar O Ar

- Dehydration of oximes OH N H2NOH•HCl P2O5 R CHO R C N R H

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

- Reduced to aldehydes with DIBAL. DIBAL RCº N RCHO FUNCTIONAL GROUP INTERCONVERSIONS 121

Azides - displacement of halides and sulfonates with azide anion

LDA, THF O O O NBS NaN3 O O O Br SO2N(C6H11)2 N3 SO2N(C6H11)2 SO2N(C6H11)2

O O TL 1986, 27, 831 O HO

NH2 NH SO2N(C6H11)2 2 - activation of the alcohol

R N + R OH + + + 3 N F N OR N O Me Me Me TsO - + EtO C PPh3 Ph P, NaN 2 3 3 N N R OH + EtO2C N N CO2Et _ CO2Et DEAD activated alcohol

+ R-OH R N R O PPh3 3 + Ph3P=O JOC 1993, 58, 5886

N3 HO O (PhO) P(O)-N 2 3 P(OPh)2 SN2 O + - DBU, PhCH3 + DBU-H + N3 (91 %) O O (99.6 % ee) Ar (97.5 % ee)

- Photolyzed to aldehydes Amines - Gabriel Synthesis O O

- H2NNH2 + R X N K N R R NH2

O O - reduction of nitro groups

R NO2 R NH2 H2, Pd/C Al(Hg), H2O NaBH4 LiAlH4 Zn, Sn or Fe and HCl H2NNH2 sodium dithionite FUNCTIONAL GROUP INTERCONVERSIONS 122

- reduction of nitriles

R C N R CH2 NH2 H2, PtO2/C B2H6 NaBH4 LiAlH4 AlH3 Li, NH3 - reduction of azides

R N3 R NH2 H2, Pd/C B2H6 NaBH4 LiAlH4 Zn, HCl (RO)3P Ph3P thiols - reduction of oximes (from aldehydes and ketones) OH N NH2

R R' R R' H2, Pd/C Raney nickel NaBH4, TiCl4 LiAlH4 Na(Hg), AcOH - reduction of amides O R' R' R N R N R'' R'' H2, Pd/C B2H6 NaBH4, TiCl4 LiBH4 LiAlH4 AlH3 - Curtius rearrangement O O O

NaN3 •• D •• •• ••

R Cl R N N N •• R N + - N2 nitrene

R N O H2O R NH2 isocyanate FUNCTIONAL GROUP INTERCONVERSIONS 123

- reductive aminations of aldehydes and ketones - Borsch Reaction - Eschweiler-Clark Reaction - alkylation of sulfonamides

Tf Tf Tf K CO , DMF N HN 2 3 N N NH HN TL 1992, 33 , 5505 Tf 110°C Na, NH3 Tf N HN Br N N NH HN Tf Br Tf Tf cyclam

- transaminiation

O N Ph N Ph NH2 PhCH2NH2 + tBuOK H3O Can. J. Chem. H+ 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 CO2R Pd(0), ROH TL 1985, 26 , 1109

- Arndt-Eistert Reaction Angew. Chem. Int. Ed. Engl. 1975, 15, 32. O O O CH2N2 hn N •• R Cl 2 Et2O R ROH R CH diazo ketone Wolff R O Rearrangement C O R'OH R H OR' ketene O O TsN3, Et3N CO2Me N2 R R

- Diazoalkanes: carbene precursors 1) NH2NH2 2) Pb(OAc)4, DMF R-CHO R-N2 JOC 1995, 60, 4725 R3N H2N N TsN 3 N2

R R R R

- Halo Lactonizations review: Tetrahedron 1990, 46 , 3321 I + I I2-KI CO2H O O H2O, NaHCO3 H O O FUNCTIONAL GROUP INTERCONVERSIONS 124

Pd(OAc)2 (5 mol %) JOC 1993, 58, 5298 CO2H O DMSO, air O (86%)

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

- Mitsunobu Reaction Synthesis 1981 , 1; Organic Reactions, 1991, 42, 335 Mechanism: JACS 1988, 110 , 6487 O

DEAD, Ph P OH 3 O R'' Inversion of alcohol stereochemistry R R' R''CO2H R R'

Amides and Lactams - reaction of an "activated acid" with amines - Beckman Rearrangement Organic Reactions 1988, 35, 1 OH O N PCl5 O

R R' R R' R NR' - Schmidt rearrangement O O HN3 R R' H+ R NR' - others

O NR2 OTf CO, DMF Pd(0), R NH 2 TL 1985, 26 , 1109

OH O O O PhCH NH 2 2 N Ph H TL 1977, 4171 AlMe3

OTHP OTHP

-Weinreb amide Tetrahedron Lett. 1981, 22, 3815 DIBAL O O O H3CNH(OCH3) •HCl R H OCH3 R OR' R N AlMe3 O CH3 R -M 1 R R1