官能团相互转化(1)分析解析

1、5-fc=c-xC=O5-gC=C-ORC=C-SR HgC(OR)2- C=Oa very common protecting group, deprotect back to ketoneOR OR、SR亠O_SjOEtH C 二 OEt、OEtH3O+ / solv (aq)Hg2+ / H3O+H3O+ / solv (aq)Hg2+ / H3O+RMgX / H 3O+ORORH3O+ / solv (aq)acid catalystH3O+rH+h2ojXCh3OhOcH3X+OCh3Jreactivity:OHOHCH3CNtpye： OR enol etherSR thioen

2、ol etherOR SRenaminevinyl chlorideORORORSR SRSRruse: 0h几Fl厂Rh ROHOROH ORHHType:H ORR ORH ORR ORR乂 ORrX ORrX OHR乂 OHacetal丄ketalhemiacetalhemiketalJunstable: only in aqueous acid stable in: basic solution: LDA, NaOMe RED: LiAlH 4, NaBH 4 organoMetal: RMgX, RLi- *via:0EtRMgXvia. cOEtOEt0R C OEt HH5-hC

3、-OHC=OO1st alcohol - R_C_HJACS, 1991, 113, 7277.AcO OAcOAc2nd alcohol1st alcoholaldehydeITHL, 1979, 5, 399.O CHOOH pdcSOPh DMSONOi. PCCii. PDCiii. Collins reagent CrO 3 - 2 Pyiv. N-oxidev. DMSO / DCCvi. DMSO / HClvii. DMSO / NHCO 3 / Nalviii. Dess-Martin ReagentCH2CI2, rt, 30 minBrOCH3NaHCO3 / Nal H

4、60 %92 %H11C5PDCCH2OHH11C570 %CHOS0CH3OOHDCCOCH3RCH2OHvia： PhCH2 DMSOOH DMSOPhCH2OHPfitzner-Moffatt oxidationJOC, 1985, 50, 1332.DMSOHClPhCHOCan. J. Chem, 1978, 56, 1268.PhSynth. Commun., 1986, 16, 1343.PhSynLett, 2002, 2041.HCH 3C 1 O SHCH3O i. pcc TH, 1975,2647. _O ii PDC(JH, 1978,2771.R _ C R- -

5、iii. Jones reagent (Na2Cr2O7-H 2SO4 / acetone)iv. Moffatt oxidation (DMSO / Ac 2O) _ _ .v. Swern oxidationvi. DDQ / dioxanevii. MnO 2 / CHCl3 JOC,佃97, 62, 5246.viii. Oppenauer zoidation Al(OiPr) 3, acetoneix. K 262O7 (s), rt solvent freeTHL, 2002, 43, 8843.%X OR _ C _ OHi. Jones reagentii. KMnO 4R-C

6、-OHAg2OPCC (pyridinium chlorochromate) (Py-HCl-CrO 3)most widely used.7 CrO3HClCollins reagent: (CrO3 - 2 Py)1. drawback: use 6 equivalent, a messy reaction2. must be very dry, fire easily; purify by CaH 23. an old oxidizing material, isolated by Collin.Swern oxidation: (DMSO, oxalyl chloride, Et 3N

7、) drawback: react at low T f Synthesis,佃81, 165./i小JOC, 1977, 42, 1991.PDC (pyridinium dichormate)Ag2O:(H2Cr2O7 + 2 Py)eg?-21. a mild oxidizing agentuse 1 - 1.2 eq. H+.-22. must be freshly prepared: NaOH into AgNO 3 (aq)3. may involve surface change, react with CO2, lightC=OO5-i.iC=OOOPhPh OPhOOHOPh

8、H3OoMCPBA5-i.2C=ONONef reactionOOOpH1McMurray reactionpH6OMeOSSPhPhKOHOO2.CH3OHH2SO4pH 6: weak acid buffer, avoid interfere with ketal groupJACS, 1977, 99, 3861NO2C-NO2TiCl 3N=O O .vi. KMnO 4 / KOHJOC, 1969, 34, 2438c-nx2ii. TiCl 3 / pH 1 or 6THL, 1981, 5235.C-NH 2Chem. Rev. 1955, 55, 137.N_ OMnO2 N

9、OaOC Hii. Watt approacha. PhCHO / MCPBA / H 3O+b. ArPhO / MCPBA / H 3Oc. NBS / KOH / H 3O+O OPh O:一 N C PhON OH3O+v. NaOH / CH 3OH / H 2SO4 / H3O+Synthesis, 1988,379.O / H3OKMnO 4ONOOi. EtsN / H3O+iii. SiO 2 / NaOH / H 3O+PhN=C_ PhON OOPhN Phiv. LDA / MoO 5-Py / HMPT / H 3O+PhPh ；一 NH 2HsO +M PhNPhN

10、O2/1. NaOHPh_NH2OOOMn OPhN. C_ Ph HPhOi. Corey approach: subtituted-quinone / H 3O+Ph NH 2 PhCHOEtsNHI OMe PhO O TiCl 3PhNHPhCHO -PhCHO PhNH 2OMCPBA .5-i5-jC-BrC=Oindrect: change to RC-OH followed by oxidationdirect:1. DMAPO / DBU / CH3CNBull Soc. Jpn., 1981, 54, 2221.NMe2ODMAPO5-k2. NaIO4 / DMFa ne

11、w methodr NaIO4 / DMFBr 150 C,品O84 %THL, 2003, 44, 1375.3. DMSO reagents:i. DMSO / AgBFii. DMSO / ZnSTHL, 1974,917.JACS, 2003, 68, 2480.DMSOvia:NMe2ON,N- D i methyl amino pyridine oxideFPh空HBr DMSO / AgBF 4R-AgBrO-MezS R6- a RC三CHb RCH2-SO2Phd C=Ce RCH(CO2H)-CH3c C 三Cf -C(O)-CH 3i CRR=CHX尸16-aRC三CH

12、亠RC三CRi. n-BuLi / RXn-BuLi: not MeLi, or t-BuLi, fire easily RX: R-Br, R-TOS, RCHO, RC(O)Rii. (Ph3P)2PdC2, CuI, EtzNH / PhIR C C H RCC PhTHL, 1975, 4467. j6-bCliii. NOMeListeric base, prevent Nu attackiv. CuI, Nal, Na 2CO3, rc CCH2CIRCH 2-SO2Ph- RC CRn-BuLi / RCHO / Ac 2O / KO tBuR C C HRCC ArR C C

13、H ” R C C RRCCH a R C C CHOH iRCl- CH2 C三 C RR- C三 C- HR- C= C- CH2- W C- R Synthesis,2000, 691.R CH2SO2Phsulfonen-BuLiRCHOSO2PhR C C ROHAc2OSO2PhR C C ROAc-HOAcSO2PhR C C RHKO tBu-PhSO2HR C C Rsulfonic acid: PhSO3H; sulfinic acid: PhSO 2H; sulfenic acid: PhSOH6-c6-d6-eC Cc_cJACS, 1975, 97, 891.HKin

14、volved: reduction NaBH 4, oxidation CrO 3.Py, prevent :-H attacked by Br2i. move to terminal use: KAPAii. protect - deprotect use: Co (CO)8 / Fe(N3)3, EtOH1.B2H6HO2.HOACchoose B2H 6, not H 2/cat:HOHOHHOFe(NO 3)3EtOHHOHPhHOPhPhPhKOtBuKOtBuCO2HCH3ClCl-OCOCOCOCO2. KOtBu3. CrO3.2Pyii. Br 2 / KOHR C C Hi

15、n fact: convert to C=C firstly1.Br2/CCI 4JACS,佃41, 63 1180.1.NaBH 4Co2(C)8OAcR 3CO PbOAc O OAcuse: Pb(OAc)4, LiCI / KO tBu / Br2/CCl4 / KOtBuR-CH CH3use: i. Br2 / CCI4 / KO tBuR CH CH3 CO2HCCCO Co CoCO CO COR C CH3CO2,Pb (OAc) 2, -OAc-Pb(OAc)4,咒 CH CH2 Br2/CC R c c hC| H 2.KOtBu HOLiCI / Pb(OAc) 4 O

16、 co2hHOC CHCo poison catHOC CHHC c-CO_ Co兰 CoCO CO COFe(N3)3： weak oxidizing agentrc 二c 一4 C三CJ6-fHN6-gNOOOHTsOHTsNHNH 2N2TsN.a COii. NH 2OH, NaNO 2 / H2SO4 / AcQ / DMAPOLDA: Li N(iPr) 2, ignored a long time, re-introduced by Michigan State U. became famous, appeared every weeki. NaBH 4, H3O+, Br2,

17、KOtBuNiii. LDA, ClPO(OEt) 2一 lmixture ofAC20 / DMAP:DMAP:N4-N,N- D i methyl aminopy ridineGerman invention, as acylating agentH2O2Na / NH 3(1)OCH3CH CH2(MVK)Robinson AnnulationHLJOC,佃79, 44, 4116.Ac2ODMAPOR C 旳忖 R Ch： oh.OAcR:R C CH/CHH2SO二 R C_Ng 警2 r上巾 /o CH3rch c HHOHR C CH30NaBH 4R C CH3.HqO+B23

18、- R C.CH2RCHBrCH 2Br KOtBuR C CHOR-CCH3J R C-C HTHL, 1967,3943.0OPO(OEt) 2IlLDAR C CH3RC_CHLDAr c chClPO(OEt) 2JI*HJOC, 1980, 45, 2526.vinyl phosphater宀iOuse: TsNHNH 2 / EtOH, heatO6-huse: LiNH 2 / NH3 (I)/ R-XClLiNH 2 / NH3 (I)RX6-i.A 一-R_C 三 C_R-JACS,佃55, 77, 3293.JACS, 1958, 80, 4599.i. NaOEt (wh

19、en X = Br)ii. BuLi (when X = -OSO 2CF3)NaOEtAr C三 C- Arvia:MePhMePhOSO2CF3HBuLiMe C= C PhJOC, 1978,43, 364.c=cc CX-CYfc=oi C=C7-a CH-CXb CH-CHXd c ce -C(0)-CH3gC三Ch C 三 CHC-OH7-ac c - CCC capplied for reactions:C_CH OHi. p-TSOH.H 2O or CSAuse*ii. weak acid: HOAc; HCO iii strong acid: H 2SO4; HCl iv.

20、 ArSeCN, PBu 3 / MCPBA2H; H 2C2O4OHC_CH OmsMsCIC_CH OAcC_Cuse base: i. RONa;use: heatuse: heatii. KOtBuH OC(S)SMeC _Cuse base: DBNC Cheat (Hoffman elimination)H NH2i. CH 3I / Ag 2O /ii. HCHO / HCO 2H / H 2O2 / heatHO7-bCCcci. DDQONCClNCClOii. chloronailClClClCliii. Pd-C; or Ni; Pt, RhPd-C(CO2H)2 / b

21、enzenePhDean-StarkRONamajoror KOtBuH2SO4heatONMeHCHOHCO 2HNMeJ-11without rearrangement;H OHno regiosiomerOH卩恥创CH3 hea-syn eliminationPhOOHi. n-BuLiii. CS2CZO 八 SMeheat0Jiii. CH 3Ib1DBNacompare:广厂0H0MsOOHNO2MeOMeO?COAc CO2MeNH2OAc ；：八 se= nCH3I (excess)MCPBAheatMeOMeO2OAc C2MeAg2。H2O2OAcmechanism:Ph-

22、Se-CN:PBU3RCH2CH2-O-PBu3minorRCH2CH2-OHPh-Se-PBu3MCPBAheatRCH=CH 2MeODDQTBDMS - OHDDQTBDMS OMeO23oC, 14h, 88%THL, 1991, 3679.7-cc_cOH OHii. CSCI2 / P(OMe)i. Zn / acetoneC CBr Brii. In / MeOH JCS.CC, 1998, 2113.i. CSCl2 / PNPhcOHOHbaseCSCI2C CO othiophosgenei thionocarbonateC一 Capplication: i. protec

23、t alkene: via Br2 Znii. purify compoundCCNal / Zn (Cu)OMs OMsvia:OH IPOCI3 / py /SnC_COCCCCC 36 oC CCCC=C 31 oC CCCC_ C 148 cZnHOAcJOC, 1978, 43, 364.Zn/HOAcBr OAc7-dCC7-d.iOCc- C Ci. WCl 6 / RLiproduct retentionRiii. Na (special structure):ii. LiPPh 2 / CH3Iproduct inversionClWCl6H1RL厂rOHLiPPh2Sn2r

24、HCH3CH3IH7-d.2Sc=c 一 C=Cuse: (EtO)3PR1R27-eOIIC CH 3-Ccuse: TsNHNH 2 / n-BuLiTSNHNH2EtOHTsNHNR C= C-CH2-CH2-CH2-OHH(EtO)3PR1R2Synthesis, 1977,1134.n BuLiJOC, 1977, 42, 1079.7-fC0CC7f 1 RC =0 RC CRi. Wittig Reaction 1953 discover (olefination reaction)use: Ph3P-CHRvia: betaine, oxaphosphetane (NMR)Q

25、use: (RO) 2PO-CHR RO = MeO-, EtO-ii. Phosphonate Wittig Reaction (Horner-Emmons Modification)water soluble, removed by extractio n(comparis on: O=PPh 3 highly soluble in orga nic solve nt)iii. Silyl Wittig ReactionMe3SiCHR-Li(Peterson Reaction)Ph3SiCH 2-Li+=THL 1981 2751 -Me3SiC H-MgBr = Ph3SiC-HCH

26、2Ph =Me3SiC-HCO2Et =JOC, 1968, 33, 780.- 1 Me3SiCH=PPh3=Synthesis, 1984,384. |=Ph3SiCH2Br + n-BuLi (exchange)=Me 3SiCH 2Cl + Mg (metal reduction)=.Ph 3SiCH=CH 2 + PhLi (addition to vinylsilane) ：=Me 3SiCH 2CO2Et + Li (metalation) :Me3SiCH2PPh3+ X- + KHiv. CH2(Znl)2_Synlett, 1988, 12, 1369.CH2v. CH2C

27、HBr2, Sm, Snb / CrCla, THFChem. Lett, 1995, 259.vi. Sulfoximide (Johnson C.)use:vii. Grignard reagent: use: TMSCH2MgClTHL, 1988, 4339. THL, 1973, 3497.OPh S CHII N Me/ Al (Hg)notOPPh3 + H C CO2Medifficult to preparePPh3 + expe nsiveun stable ylid gives cis (Z)stable ylid gives trans (E)not good for

28、Ph 3P=CH fun cti on as base:RCRPPhRR PPh+PPh3Q人Ph(OAc) 4PhCHNMeAl (Hg)1. TMSCH 2MgCl2. NaOAc, AcOHN. R. if use: PhaP-CHRdue to steric hindranceH O 丁 SiMe3 via:C/ %R Rmethylenationadvantages over the Wittig:1. by-products are more easily removed,2. reaction suffers less from steric effects.7-f.2RCORC

29、CRR C O 04R-R N _N r CRRH HR N_ NCR - SPh(OAc) 4RRR2COC_ NRPPh3CH2S.C_NHNHRRPPh3RRRC CR _ R1. h2s2. Pb(OAc) 43. H3O+OOOOOii. McMurry CouplingTiCI 3-LiAlH 4 / THF JACS, 1974, 96, 4706.TiCI 3 / Mg(BASF, 1973,2147.TiCI 4 / ZnChem. Lett, 1973,1041.TiCI 4 / Kjoc, 1978, 43, 3253.)7-gCCCCnot use H2 / Pt: m

30、ight convert to alkaneRR C_C RC二CH“Rform trans alkene: i. Li / NH 3; or other IA metalsii. Li / EtNH 2iii. LiAlH 4 / THFform cis alkene:H2 / Ni2B (P-2 catalyst)TEtMeH 2 / Pd-CaCO3 (Lindlar catalyst)EtC三 C-Me J cH 2 / Pd-BaSO4Hiv.v.vi.N2H2HCHO / Pd-C / Et 3N7-hC CHC C Ri. R2BH / Br-CN (hydroboration)

31、ii. DIBAL / n-BuLi / CH 3l (hydroalumination)iii. Cp 2ZrClH / RX (hydrozirconation)all form trans alkene:C = CHDIBAL RHR_C=C_H . .、C_CHAIR 2Ph C CCHOHCHO,Pd-CEt3NPh C CCHOJOC, 1980, 45, 4926.n -BuLiCH3IRHC- CH _RHC CH- CHCP0CIHR c H RX R“HR_C=C_H_ C CC_CH 1 ZrCP 2HRCl7-irc=c -ccJJapplication: protec

32、ting groupOHc=cc=cBrOHdihalideLAHPhSO2ClNaBrc=cc=chalohydrincO2HcOOHOc=cepoxidec=cRONaOSOc=cdiene-olefin additionc=cPhdiradicalPhPhCO 2EtCO2Et180CH2200 oCCH 2EtO2C CO 2EtX XH XC CJACS, 1998, 100,877C CCO2EtCO2EtCO2EtCO2Et1. OH-2. H3O+double bond might moveviaviaviaviavia“C cnot forH OH7-jBrC-OHNO2CH

33、3cc尬NO2Ph3P CH3 Br-OH MnO2MnO2 / Ph3P CH3 Br-/ MTBDMTBDSynlett, 2002, 215.MTBDin situ alcohol oxidition Wittig rxn8-aC-X8- a C-OHb C-NH2c C=Od C(O)Ze C-HC-OHC-X1.O OSNSoChem. Rev., 1996, 96, 1737.FCHCl 28-a.i8-a.28-a.38-a.4C-OHC-FrC-OHL,C-Cl_/C-OH、C-Br1.HBrO O2. F3S-NEt2 (DAST) $ 500 / 125 gJOC, 199

34、3, 58, 3800.。CH33. CF3CHFCF2NEt2 (Ishikawa reagent)O1. SOCI22. HCONMe 2 /ci3. COC12 / DMF4. CCl4 / PPh35. HCl / ZnCl 26. HCl fit for 3PBr3 Can. J. Research, 1932, 7, 464.ON1. CF3CHFCF2NEt2OCH3-OH 2. HOAc / iPrOHOOHFNHCOCHCl 2ClN N八ClHCONMe2JOC, 1983, 48, 2625.Cl-Nrd ale, directlyMe OH EHNMe2O人Cl MeO

35、Org. Lett, 2002, 4, 553. EtHMe HEt、lvia:fVf OHCCl4 .f ClPPh3Can .J .Chem, 1968, 46, 86.ClHClOHZnCl2fit for 1 st aleClJACS, 1938, 60, 2497.N+Br3-H厂C-OH *C-IJ(JOC, 1980, 45, 1638.TMS-Br (HMDS / PyH Br 3)3.1. HIPI3YYOH OHBr OHgood for 3 rd ale.+ f SL Si、 prepare in situ(HMDS)(PyH Br3)i BrTMS-Br2. PI32.

36、 PPh3 / I2CH3OHCH3IJCS, 1905, 87, 1592.JACS, 2003, 125, 1458.3. TsCl / C6H6 / NaI Intermediate. Org. Chem, 1988.OTBSPPh3 / I2OTBSBnO OH BnOMe OH 96 %芝 I MePBr3$ 35 / 1000 gPBr3$ 65 / 500 gPI3$ 80 / 50 g8-b C-NH 2 C-XC-NH 2 C-FNaN02 / HCI / HBF 4 /8-cOCF 2Br2 / ZnF FJCS.PT I, 1993, 335.58 %8-d C(O)Z

37、- C-X8-d.i c(o)z c-ci8-d.2 C(O)Z C-BrL0齐rClClRhCI(PPh3)3尹O1. AgNO 3/KOHR- C- OHR- Br(Chem Rev., 1956, 56, 219Ber. 1942, 75, 296.2. Br28-eC-HC-X8-e. i C-HC-F8-e. 28-e. 3ii. F-TEDA-BF 4iii.Chem. Rev., 1996 , 96, 1737.JCS.CC, 1994 , 149.F2-N2 / CFCl 3-CHCl 3iv. HF / electrolysisalready industrilizedv.

38、NF3O / TBAH / CH3CNC-CHJOC, 1988 , 53, 2803.L-C-H C-X X = Cl, Br, INBX / Mg(CIO4)2c-h C-IuI 2/HNO 39- a C-XPhCH 2C(O)CH 3F +PhCHC(O)CH 3FFadamantaneF2 -N 2CFCl 3-CHCl 390 %OHF-TEDA-BF 4CH 3Me-CN,TEDA=triethylenediamineOHArR55-90 %1. regioselective fluorination at the more substituted positions2. ele

39、ctrophilic in natureHF1electrolysis1.4-1.6 VR = CH 3CO, COCF 3, CCl 3, NO 2anode: Pt or NiTHL, 2003 , 44,2799.TBHA: TetrabutylammoniumhydroxideOOOOOA ANBXAAR1”R3-RiR3NBX:N- XMg(CIO 4)2vXH R2XR2OJOC,2002 , 67, 7429.X = Cl, Br, IJACS, 1917 , 39, 437.)9-aC-X C-CH 3(ch 3)3aiBrMe3AICH2CI298 %bridgehead m

40、ethylati onOrganomet. Chem. Rev., 1996,4, 47.4-e3. NH3 (excess) / RaNi / H2catalytic reductive amination4. PhNHNH 2 / Al (Hg)via: hydrazone 5. NH4+HCO2-Leuckart reaction6. RNH 2 / n-Bu 2SnClH / HMPASynthesis, 2000, 789.儿NH 3N. NHPh Al (Hg)immonium saltCO2PhNH2Ph CHOPhn-Bu2SnCIH HMPANH 2HPhNHNHN_ NHP

41、hH HN(radical) 宝 HNHNHPhC=O - C-NX.Jreductive amination!1. RNH2 / NaBH 3CNmost general2. Me3SiN3 /LiAIH 4via: acetal / ketal type exchange4-f C=C C-C-N、丿B2H6 / H2NOSO3HC=C C-C-NH 2 B2H6 / nh2ciB2H6 / H2NOC=C C-C-NHCOCH 3CH3CN / H3O+4-g4-hR-CNR C NH2r-c-nh2R4-g.a form R-C-NH24-g.b form R C-NH?RR C NH

42、R1. LiAIH 4AIH3 / THFBrCN AIH3THFRLi / NaBH 4 TH, 1989, 30, 5137. JI RMgX / NaBH 4JOC, 1993, 58, 4313.RMgX /Li/NH *1)joc,佃87, 52, 3901.R2CuLi NaBH 4th, 1989, 30, 5139.R CH2 NHRR- C= NJOC, 2000, 65, 8152.GRM / HR- C- NH2R”2. NaBH3(OCOR)3. B2H64. EtaO+ BF4- / NaBH 45. P4S10 / RaNi6. Lawessons reagent

43、/ RaNiEt30+: Et source, convert to good leaving group; not use EtBr different from: HC(OEt) 3 dehydrating agent;H2C(OEt)2 (ketal agent)R-CH2NHRHofmann (see below)R CH2 NHROR CH2 NH200KOHR- NH b OCHPhI, OAcPhOAcPhR C N I7CH3OHR N= C= 04-iCH2COOH-RCH2 C ZCurtiusSchmidtOOOOCO2Hco2hco2hCO2EtOCO2EtOBu2Al

44、H1.NH2OHPr- sourceONHHofmannBr2KOH / CH 3OHJACS, 1981,103, 7368.JOC, 1993, 58, 2478.RCH2C CH 3R CH 2_ c CH; anti-migrationBeckmann: NH 2OH / TsCl / H 2OH2 / Pd-CH- sourcerch2c_nh2NH 2Phl(OAc) 2OII RCH2C OHRCH2 C ClOTs NOR CH2C NH-BrCurtius: NaN 3 / H 2Omost usefulN TsO RCH2 C ZR CH2 NH 2R CH2C CH3o 2.TsClO11RCH厂CNH2PhI(OAc) 2 KOH / CH 3OHOR CH2 C OHH2OCH2 N- C CH3-CO2Och2nh2OR CH2C NH2N +1