Functional Group Interconversions - Vanderbilt University

1 Functional Group Interconversions 119 Functional Group InterconversionsC&S Chapter 3 #1; 2; 4a,b, e; 5a, b, d; 6a,b,c,d; 81sulfonates2halides3nitriles4azides5ami nes6esters and lactones7amides and lactamsSulfonate Esters- reaction of an alcohols (1 or 2 ) with a sulfonyl chlorideROHROSOOR'CH3CF3CH3R'SO2 Clsulfonate esterR'=mesylatetriflatetosylate- sulfonate esters are very good leaving groups. Elimination is often acompeting side reactionHalides- halides are good leaving groups with the order of reactivity in SN2 reactionsbeing I>Br>Cl. Halides are less reactive than sulfonate esters, howeverelimination as a competing side reaction is also sulfonate esters can be converted to halides with the sodium halide in acetoneat reflux.

2 Chlorides are also converted to either bromides or iodides in the samefashion (Finkelstein Reaction).ROSOOR'RXX-X= Cl, Br, IRClRINaI, acetone reflux- conversion of hydroxyl groups to halides: Organic Reactions 1983, 29, 1 ROHRX- R-OH to R-Cl- SOCl2- Ph3P, CCl4- Ph3P, Cl2- Ph3P, Cl3 CCOCCl3 Functional Group Interconversions 120- R-OH to R-Br- PBr3, pyridine- Ph3P, CBr4- Ph3P, Br2- R-OH to R-I- Ph3P, DEAD, MeINitriles- displacement of halides or sulfonates with cyanide anionRXKCN, 18-C-6 DMSORCN- dehydration of amidesRNH2 ORCN- POCl3, pyridine- TsCl, pyridine- P2O5- SOCl2- Reaction of esters and lactones with dimethylaluminium amideTL 1979, 4907 JOC 1987, 52.

3 1309 OOArMeMe2 AlNH2 ArH3 COHNC- Dehydration of oximesRCHORHNOHH2 NOH HClRCNP2O5- Oxidation of hydrazonesNNMe2 OOCNT etrahedron , 39, 2009(97%)- Reduced to aldehydes with NFUNCTIONAL Group Interconversions 121 Azides- displacement of halides and sulfonates with azide anionSO2N(C6H11)2 OOLDA, THF NBSSO2N(C6H11)2 OOBrNaN3SO2N(C6H11)2 OON3SO2N(C6H11)2 OONH2 HOONH2TL 1986, 27, 831- activation of the alcoholROHNFMe++TsO -NORMe+NOMeRN3+ROH+EtO2 CNNCO2 EtDEADPh3P, NaN3 EtO2 CNNCO2 EtPPh3activated alcoholROPPh3+RN3+Ph3P=O+_R-OHOHO(PhO)2P (O)-N3 DBU, PhCH3 ArOP(OPh)2O+ DBU-H+ + N3-SN2( % ee)ON3( % ee)(91 %)JOC 1993, 58, 5886- Photolyzed to aldehydesAmines- Gabriel SynthesisN -OOK+RXNOORH2 NNH2 RNH2- reduction of nitro groupsRNO2 RNH2H2, Pd/CAl(Hg), H2 ONaBH4 LiAlH4Zn, Sn or Fe and HClH2 NNH2sodium dithioniteFUNCTIONAL Group Interconversions 122- reduction of nitrilesRCRCH2 NNH2H2, PtO2/CB2H6 NaBH4 LiAlH4 AlH3Li, NH3- reduction of azidesRN3 RNH2H2, Pd/CB2H6 NaBH4 LiAlH4Zn, HCl(RO)3 PPh3 Pthiols- reduction of oximes (from aldehydes and ketones)RR'NOHRR'NH2H2, Pd/CRaney nickelNaBH4, TiCl4 LiAlH4Na(Hg)

4 , AcOH- reduction of amidesRNOR'R''RNR'R''H2, Pd/CB2H6 NaBH4, TiCl4 LiBH4 LiAlH4 AlH3- Curtius rearrangementRClORNO - N2 RNO nitreneNaN3NN +RNOisocyanateH2 ORNH2 Functional Group Interconversions 123- reductive aminations of aldehydes and ketones- Borsch Reaction- Eschweiler-Clark Reaction- alkylation of sulfonamidesNNNNNNHNTfTfHNTfTfK2CO3, DMF 110 CBrBrNHNHHNHNTfTfTfTfNa, NH3cyclamTL 1992, 33 , 5505- transaminiationONPhtBuOKNPhNH2H3O+PhCH2N H2H+Can. J. , 48, 570 Esters and Lactones- Reaction of alcohols with "activated acids"- Baeyer-Villigar ReactionOrganic Reactions 1993, 43, 251- Pd(0) catalyzed carboylation of enol triflatesOTfCO2 RCO, DMFPd(0), ROHTL 1985, 26 , 1109- Arndt-Eistert ReactionAngew.

5 Chem. Int. Ed. Engl. 1975, 15, ketoneh RCHO ROH Wolff RearrangementRCOketeneR'OHHROR'ORCO2 MeOTsN3, Et3 NRN2O- Diazoalkanes: carbene precursorsR-CHO1) NH2NH22) Pb(OAc)4, DMFR3NR-N2 JOC 1995, 60, 4725 NRRH2 NTsN3N2RR- Halo Lactonizationsreview: Tetrahedron 1990, 46 , 3321CO2HI2-KIH2O, NaHCO3 OOOOII+HFUNCTIONAL Group Interconversions 124CO2 HPd(OAc)2 (5 mol %)DMSO, air(86%)OOJOC 1993, 58, 5298- SelenolactonizationOHOOOPhSeOOPhSeCl, CH2Cl2H2O2 JACS 1985,107 , 1148- Mitsunobu Reaction Synthesis 1981 , 1; Organic Reactions, 1991, 42, 335 Mechanism: JACS 1988, 110 , 6487RR'OHDEAD, Ph3PR''CO2 HRR'OR''OInversion of alcohol stereochemistryAmides and Lactams- reaction of an "activated acid" with amines- Beckman RearrangementOrganic Reactions 1988, 35, 1RR'ORR'NOHRNR'OPCl5- Schmidt rearrangementRR'OHN3H+RNR'O- othersOTfONR2CO, DMFPd(0), R2 NHTL 1985, 26 , 1109 OTHPOOPhCH2NH2 AlMe3 OTHPOHNHPhOTL 1977, 4171-Weinreb amide Tetrahedron Lett.

6 1981, 22, 3815 ROR'OH3 CNH(OCH3) HClAlMe3 RNOOCH3CH3 DIBALR1-MRHORR1O