Transcription of Functional Group Interconversions
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.
2 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. 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)
4 , 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), 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.
5 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. 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.
6 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. 1981, 22, 3815 ROR'OH3 CNH(OCH3) HClAlMe3 RNOOCH3CH3 DIBALR1-MRHORR1O
