官能团转化全图解

1、有机合成图示图解Lemsay第63页2020-3-4Functional Group InterconversionC-HC-OR1- aC-OH2-a C-OHbC-Xb C-(OR) 2cC-NH 2dC-Sc C(O)OReC=Od C-HfC=Ce C=CgC-CNf C-CNhC-CO 2HiC-CHOjC(O)XC-OH 一C-N -3- a C-H4- a C-Hb C-ORb C-Nc C-Xc C-Xd C-NH 2d C-OHe C-OCH 2ORe C=Of C-OC(O)Rf C=Cg C-OHg C-C(O)Zh C=Oi C=Oh C Nj C=CC=O5- aC=

2、Ob C=Sc C=N-OH, C=N-Hd C三Ce C Nf C=C-OR; C=C-SRg c(or)2； C(SR)2 h C-OHi C-NH 2; C-NO 2j C-Brk C-HC三C飞C=C6- aRC 三 CH7- a CH-CXbRCH 2602Phb CH-CHcC三Cc CX-CYdC=CXd c - ceRCH(CO 2H)-CH3f-C(O)-CH 3e -C(O)-CHf C=OgOOg C三ChXO Oh C 三 CHiCRR'=CHXi C=Cj C-OH3C-X -C-CH 38-a C-OHb C-NH 2 c C=O d C(O)Z e C-H

3、9- a C-XC-H1-a C-OH b c-x c C-NH2 d C-Se C=O f C=C g C-CN h C-CQH i C-CHO j C(O)XJ. Org. Chem. 2000, 65,-a C-OH C-H(1). for 1', 2' alcohol:i. “sCl / LiAlHOCH3- :一 S-ClRCH2OH dry PyLiAlH4 > RCH-HRCH>-O-S-CH3IIO OIIRCH2-OSCB11Otosylatemesylatetriflatetoluenesulfonyl chloride s$ 30 / Kgme

4、thanesulfonyy chlorid $) 30 / Kgpurification textbookdry pyridine: from C2aHnd distilledii. PhSiHCl / InClPh PhYOHCHC2 rt, 3 hrHJOC2001 66 7741.PhSiHCl / InCl Ph Phindium trichlorideInC3 a unique Lewis acid catalyst,acceleratedeoxgyenationSnBuSSO-CO-Ph . OCOPh + *thiocarbonate(an ester)steric OK(2)

5、. for 3' alcohol:CH3SCH3i. ClC(S)OPhn/BuSnH CH3kOH Cl-C-O Ph r-Bu3SnH CH-U H ACH3CH3ii. E3SiH / Lewis acid JOC200065 6179.1-b C-X -A C-Hi n-Bu3SnH / AlBN(1). free radical reductionii NaBH / InC3 / CgCNn-Bi3SnHAIBNBi3SnH: (l), easy to removePh3SnH: (s), hard to removeMe3SnH: too volatile, toxici

6、LiAlH4JACS,2002 124,906. radical reagentJACS1972 94 8905.(2). hydride reduction NaBhl (JOC1969 34 3923.THL,19693095.:iii NaBHCN NaBHCN: stable at pH 5-6 iv LiBHE3 (super hydrideJOC,1976 41 3064.hygroscopic, dried self, suggest: buy small amount each time unstable in acid, formgas; stable in weak bas

7、e(3). metal reduction Na / NH Li / NH3； Na / EtOHii Zn; Fe; Sn; MgBr Mg / E2O H2O(Grignard reagent)1-C C-NH 2c C-HJ-I(1) . RCH2NH2 "Tse1 » BuL；LiAlH ；(2) . Ar-NH2P-TsC：NaH.NaH 尸NH2C1NaNO2 H3PO2(3) . Ar-NH 2.RCH2-HAr-H(4). RCH2NH2RCH2NMe3XAg2ORCH2NMe3 OH-1-d C-S C-H(1). Raney Ni(2). Li / NH

8、3(3). LiAlH 4 / CuCl2 NaBH4 / NiCl2JCS Perkin Trans 1,1973,654.NaBHEt3 / FeCl2 (or CoCl2, VCl 3)ArSO2ClRCH2NH2 Hinsberg's testClp-TsCl CHRCH2NH- SO2Ar BuLQRCH2N- SO2Artosylamide-BuHSO2Arprii 卜产LiAlH 4rch2nRCHzHSOzAr tosylimide weaker C-N bondSO2Arvia: Ar-NNaH_NH22 - ArSO2HAr N 工 NHA- Ar N- N

9、7; Ar-HJOC, 2001, 66, 8293.JR=CH2* R-CH3radical mechanismRaney Nickel: Ni - Al alloy, suspension burn filter paper if dry mechanism uncertain, probably radicalChemistry: R-SH R-S-R R2SO R2SO2R-SS-Rremove: Hg+; Ni1-e C=OC-Hbest suitable for aryl ketone (ArCOR); not good for conjugatekejOnepreparation

10、: HgiCtb ZnBF3, CHC2HSHHS 、S H thioketalRa(Ni)(1). Clemmensen reduction: Zn-Hg / HQcidicsimilarSn / HClOH OC6H130thioketal: inert to LAH; react with RaNi; smell terrible and stay long; discard shoses(2). thioketal:lSH匚SH/BF3 CHC2 RaNineutral(3). Wolff-Kishner reductioNHU 0H heat( basic(4). Pd-C / H2

11、NBU mild, efficient .OPd-C Ph PhHCONH4(5). Tosylhydrazone reduction (Shapiro reaction):Synthesi2i00,1 162370(modified Wolff-Kishner reductjon)HNH/ RED(6). enol derivatives:f2O /(7). ESiH / C3COOHJOC1 97338, 2675./ H2 / PtOlimit: for -H compd.OHOHmajor side-product: drawback of the reactonON2H4H 卜H-，

12、N N TsHH for acyclic, may C=C side productRED choice: MeLi; NCBH(good)LAH, NaBH 2 group compete at Stanford U.E2H6 very flamable, fire if shoot out from syringeOB HOH O i ii C-COOIIiiCF3S O_SCq<1IIOOOTf HC-CH2PtOH HCCH/ 1-fC=CC-C-HH2PtO2HO(1). H2 / cat(2). HN=NH (diimide)JOC, 1993 58, 4979.(3). B

13、2H6 / RCO2H, heatsoluble in org solvent, 9 Ph group$ 50 / 25 gDprepare isotopeOEtOEtOEtvia:OHJOC, 2001, 66, 8690.RH一 H N N H-2 CO2OH- HO2C N- N CO2HO H H OO-via: .CH3CO2D- B R Rcatalyst:Pd-CPtO2Rh-C; Rh-AhO3；RhCl(PPhO3 Ni.n-Bu2snI / MgBr2-Et2O /OEtn-BuzSn： H3O;MgBr2-Et2OH2 , PtO2stereoselcetive: sam

14、e side as OH (due to H bond)RhCl(PPh?)3Wilkinson's catalyst: regioselective, prefer isolated double bondRTFA , 60 Cin acetic condition R = NHAc , NH2JOC,2002 67, 7890.CO2MeN2H2: unstable; generated in situ from "DEAD" (diethyl azodicarboxylate) (.JCS, PT1,1986, 546 or from: N2H4 + H2O2

15、; N2 H4 + Cu(II) + O2; NH20H + NH2OSO3EtO2C-N-N-CO2EtH R ROSn 'llRR-RC- CR-N2JACS, 1979, 101,RhCl(PPh3)3benzene 12 hrsyn-additionRC、RHnot radical mech.CO2Me1-g C-C=Nc C-HCN: X (pseudo halogen), form KCN, NaCN with IA elementsnot quite same: not for-H.K / AI2O3 JOC,1980 45, 3227 K/HMPA(2). Na / N

16、H3r 一 C_C=N characteristcs: IR, CMRwhich is + ? toxic?1-hC-CO2HC-H.particular structure: -CO2HMPA: hexamethyphosphoamide (Me2N)3P=O=HMPT: hexamethyphosphorict riamide (MeN)3P=O highly toxic, cancer suspected agent? modified yes for white mouse, uncertain for humanb.p. 230 Cto: N N/ Y、O(2) . normal s

17、tructure: SO。PhSeH /n-BicSnHother Cl sources: PCl(COCloxalyl chloride .(3) . organic electrochemistry'OOOSOC2PhSeHn-Bu3SnHRCHh-C-OHa RCH2 C-Cl RCH-C SePhRCH H(radical mechanism?)organoselenium chemistry1-i*CHOC-H(1) . RhCl(PPh 3)3 (Wilkinson's cat)(2) . Rh(DPPD) 2+ Cl-DPPD = Ph 2P-CH2CH2-PPh

18、2ClPPh3RhPPh3'PPh3-PPh3HI PPh3Rh' PPh3rearrangement1-jC(O)X - -CH 3HSiEt 3 / B(C6F5)3c 0 .(RRPPh3CPPh3O' ClR- H +reductive eliminationClRhCO?PPh3PPh3R- CH3JOC, 2001,66, 1672.RC-OR2- a RC-OH b RC-(OR) 2 c RC(O)ORd RC-He RC=Cf RC-CN2-a RC-OH2-bRC-ORapplication: for protecting groupgenerate

19、 H2, or butane gastrimethyloxonium tetrafluoroborate(1). Me: base / CH 3-XRC-OCH 3base:NaH, n-BuLi, Ag 2O -JOC, 1988, 53, 2985.JCS, 1930, 2166.CH 3-X: CH 3I; CH3OSO2R; (CH 3)3。+ BF4-, (CH3)2SO4 一(2). PhCH 2-: base / PhCH 2-XRC-OCH 2Ph = RC-OBZl = RC-OBn(3). allyl: base / /、，BrRC-OCH 2CH=CH2(4). t-Bu

20、: acid cat / 彳RC-O tBu(5). trityl: py / Ph 3C-BrRC-OCPh 3 = RC -OTr(6). silyl: Et 3N / R3SiClRC-OSiR3(7). acetal / ketal: (see 3e)(8). ArF / CsFRC-(OR) 2PhCH2-X:acid: h 2sO4H3PO4BF3-Et2OEt3N / TMS-Cl-N/ TBDMS-ClN fHTBDPS-ClRC-ORORR ORactivator / hydride sourceOR-O(1). h / HSiCl 3(2). HCl / NaBH 3(CN

21、)(3). AlCl 3 / LiAlH 4Me group:i. Williamson ether synthesis, S N2 typeii. not a good protecting group, too stable to convert back to alcoholPhCH2-ClPhCH 2-Br: reactivity goodPhCH2-I: reactivity better than PhCH 2Br, generated in situ, PhCH 2Br + NaiBenzyl- group:i. abbreviation: benzyl = PhCH 2 = B

22、zl = Bnii. deprotecting: H 2 / Pd-CCHCH 3SiClPhNO 2FROHROCsFSiClPhCH 3SiCH3Clt-Butyl group:Willianson synthesis (base, S n2) not work: elimination side-product with baseTrityl group: (tirphenylmethyl)i. SN1 reactionii. abbreviation: triphenylmethyl = trityl = -CPh 3 = -TrBr base(RO-Tr)CHii. advantag

23、e: high MW, easy to handle (small amount become large amount)Silyl group:NO2RCH2 ORRCH2- OCH2CH2OH.Willianson synthesis OK: Si - Cl bond longi. stability of silyl in acid/base: RC-O-TBDPS > RC-O-TBDMS >> RC-O-TBSii. abbrev.: TBDMS = tert-butyl-dimethylsilyl = TBS =aromatic substitution reac

24、tionusually contain NO 2, F as leaving groupOCH 3 HClOCH 3"，为OCH 3OCH 3AlCl 3O LiAlH 4OH2-c2-dORC OR(1). hv / HSiCl 3RC-ORSiCl3 radical mechanism: t-BuORaNi with C=S(2). HCl / tBu-OO- tBu JOC, 1974, 39, 2470.'(3). Lawesson reagent / RaNi(4). BF 3 / NaBH 4 limit for: lactoneOCH3O：P。cH3S P4S1

25、00.Lawesson reagent -HClLawesson reagentJOC, 1983,48, 1127.RC-HRC-OR(1). I 2 / Pb(OAc) 4 / hvAngew Chem Int Eng., 1964, 8, 525.limit: for 56 ring neighboring OH groupOHI2 / Pb(OAc) 4 » hv(2). Organoelectro Chemistry: e - / Pt, R4NOTs(3). NCS / MeOHJOC, 2002,67,4498.limit: for allylic alcoholPhO

26、HR4NOTsPhH H HN o:NHtBu-OO-tBuSArO RaNiO Ar一 OOBF3O ArNaBHOAre / PtPh(79 %)OR MgBrsee mech-13O I HOHONH2NCSMeOHH 0cH3N0INHNH22-eC-C-ORC_O_C C=C-OR2-e. i C =COEtC-C-ORh2oHCHOHCHO (aq)O(Synthesis, 1980, 871.mCPBA(+)-diethyl tartratestereoselectivechiral sourceHOHOOH OHC丛COHg(O C CF3)2t-BuOOH, Mo(CO) 6

27、Oracemic productsCO3H MCPBA(m-chloro peroxy benzoic acid) stable solid, 85 % (contain MCBA) for safetyCO2EtH 1 OH HO ：= HCO2Etlimit for allyl alcohol, high e.e.co2hCO3H peroxybenzoic acidHOBrH2OSharpless o OOEtOHHg - OrC CF3NaBHperacid:CF3CO 3Hgood resultCO3Hi. Hg(OCOCF 3)2, ROH / NaBH 4ii. HCHOPrin

28、s Rxn2-e. 2 C Ci. peracidii. via halohydrin: HOBr, H2O / K2CO3iii. Sharpless asymmetric epoxidation: t-BuOOH, Ti(O iPr)4 / (+)-diethyl tartrateiv.v.KHSO 5 potassium hydrogen preoxideconvenient, inexpensive, powerful.via:OHracemic productsOHtrans-diaxial attack!BrHOBr generation: NBS + H 2O + DMSOJOC

29、, 1982, 47, 2670. JOC, 2001,66, 521.vi.2-e.3|C=C2-f C-CENJOC, 1980, 45, 4758.JACS, 2001 ,123, 2933.HO 2cHO 2cC=C-ORBr2 / ROHHeterocyclic Chem, 1990, 27, 583.via:OHEtOHEt C= NEt-HClOEtC- OEtOEtJACS, 1942, 64, 1825.H 2O2, t-BuOH, MnSO 4 / NaHCO 3, pH 8 new, cheap, simple, green chemistry- C-C-ORROH /

30、HClOHconversion:OHOAc OAcOAcOSO2MeOHOSO2MeC-OH3- a C-HC-NH2C-ORC-Xe C-OCH 2ORC-OHC=O C O3-a C-H3-a.13-a.23-a.3C-OC(O)RC=C-C-OHNH2NO20OHPhI(OAc)-O 2-Mn(TPP)JACS, 1983, 105, 2920.JACS, 1983, 105, 3515.indirect(3). X2 / hv / OH -SeHO，:OHOHJACS, 1972, 94, 7154.SeC2HOHfor allyl H:OH(1). PhI(OAc)-O 2-Mn(T

31、PP)(2). organic electrochemistryHOMe3SiCl念Se4 H O - OPhH2OOSiMe3 MCPBA .Ph。OHJOC, 1975, 40, 3427.)H3O(1) Me3SiCl / MPCBA/H3O+Ph1. Me3SiCl2. MCPBAOHPhPhOSiMe3OH IOH(2). O2, LDA, (EtO) 3PJACS, 1975, 97, 6909.RO(EtO)3P CO2RO2, LDA, ROvia:ROOROOH CO2R.PO IOEtOEtRH2OOHSe(OH)2OPhOSiMe3OOHPhL3-b C-ORC-OHap

32、plication: deprotectingi. TMSIii. BF3-Et2O / R-SH (or HS-CHCHaSH)Me3Si-ISiMe3 I-RCH2-O-CH3 RCH2 O,RCH2-O-SiMe3 RCH2-OH-ICH3 - CH3I.Me: RC-OCH3iii. BBr3 / CH2Cl2, 0-10 Civ. AlCl3 / RSH THL, 2001, 42, 9207.BF3RCH2-O-CH3-RCH2 ORSHRCH2-OHv.HCl- / heatvi./ Lil, heatMeO-CO2Me AlCl； HOCH3- RSCH3CO2Me(2). P

33、hCH2-RC-OCH2Ph = RC-OBZl=RC-OBni.ii.H2 / Pd-COClCN , OHClCNO- CH2O- CH2OCH3 O(3). allyl:RC-OCH2CH=CH2RhCl(PPh)3, H3O+JOC,1973, 38, 3224.t-Bu:RC-OtBui. TFA (CF3CO2H)need stronger acidii. HBr / HOAcH(5). trityl:(6). silyl:iii. TMS-IRC-OCPhs = RC-OTrtriphenylmethyli. HOAc: weak acid: good leaving group

34、ii. H2 / Pd-C: reserve, too strong, might affect other groupRC-OSiR3-SiMe3-SiBuMe2-SiBuPh2i. F-: HF, Py-H F; n-Bu4N+ F Si - f： 140 Kcal/moii. mild base: not for TBDPSorganic base: TMG Organic Letters2003, 5, 209.iii. mild acid: only for TMS, not for TBDMS, TBDPSif HOBr: OK for TMDMSOR TMGJOC,1987, 5

35、2, 4973.OCH3heatH2 / Pd-C-CH3ClOH-tolueneOCH3OHH3O+-EtCHOOHHOH-Me3C+OCOCF3, OlCF3CO2HCH3(CH2)11- SH odorlessOHRhCl(Pfh3)H 0 cpm HOAcOH-PhsC-CH3CN1h R = TBDMS, TBDPS, AcNHTMG: N N1,1,3,3-Tetramethylguanidine3-c3-d3-eC-X - c-ohnot practically useful: R-OH cheaper than R-X(1) . OH -(2) . KO 2 / DMSO JO

36、C, 1975, 40,1678. THL, 1975, 3183.(3) . Ag 2O / H2OC-NH 2C-OH(1). HNO 2 / H3O+R-OC(O)R R-OH(1). Symmetry:ketal: use H 3O+acetal: use HaO+(2). unsymetry:RO-MOMi. H3O+; ii. HCl / MeOH;RO-MEMRO-MTMRO-THP(2). Na2Fe(CN) 5(NO) / K 2CO3 / H2O RO2C- (CH2)3cHRRO2C- (CH2)3cHR-K2CO3 / H2OJOC, 1986, 51,3913.RO-

37、HCH3OCH2ClRO-CH2OCH3JOC, 1984, 49, 3912.iii. BBrMe 2i. H3O+; ii. ZnBr 2 / CH2cl2; iii. BBrMe 2HgCl2 / CH3CN (aq.)p-TsOH / MeOHactually, acetal exchange rather than hydrolysisRO-MOM highly toxic, world top 10 killer, discardH3O+RO-CH 2OCH2CH2OCH 3 CH 3OCH 2CH 2OCH 2ClRO-CH 2SCH3 _ H3O CH3SCH2ClR OH3O

38、+p-TSOHor CSARO-H not toxicRO-HRO-Hnot dangerousSO3HCH p-TSOH(p-toluenesulfonic acid)SO3HOCSA (camphorsulfonic acid)THP: tetrahydropyran3-f3-gO II R'-C-O RR OH(1). base: KHCO (or K2CO3, NH3) / MeOH;(2). acid: H3O+common esters:formate = HCORtrifluoroacetate = C3CO2RNaOH (1 %, or 0.5 N) acetate =

39、 CHCOR = ROAcelectron: Na / NH3(3). RED:hydride: i LiAlH 4ii. NaAlH2(OCH2CH2OCH3)CH3O2CCO2cH3 NaAlH2(OCH2CH2OCH3)2benzoate = PhC2R = ROBzpivalate = tBu-CO2R = ROPvAGIEE,200241, 3028.C6H6, r.t.HOOHKHCC3 (or K2CO3 or NH) / MeOHKHCC3 (or K2CO3 or NH-) / MeOHKHCO (or K2CC3, or NH-) / MeOHNaOH (1 %) / Me

40、OHNaOH (0.5 N) / EtOHC-OHC OHMitsunobu inversion Synthesis1 981, 1.PPh3 / DEAD / RCQH / OH JOC,1987 52, 4235.J*PhCOHPPh3 / DEADEtO2C- N-N - CO2EtROHPPh5. EtO2C-N NH- CO2EtROHPPhB*EtO2C N NH CO2EtPhCOHLIPh FPh phO-* OH J, Ph C OR R-O-H3-hC-OCOH(1). regioselective:LAH -NaBH 4B2H 6 -almost all: ald, ke

41、tone, acie, ester, acyl X, anhydride-not for acid, ester (but LiBH not for ester, acyl X, anhydride;3-i(2). stereoselective: from top:LiAlH4;from bottom:NaBH 4; Na / NH 3Synthesis, 1994,1007Al (0 iPr)3 / i PrOH IrCl 4 / iPrOH / P(OMe) 3LiBH( secBu) 3 (3). HCHO reagent:HCHO/KOHHCHO / Ca(OH)Meerwein-P

42、ondorf-Verley rxnHenbest rxnH. C. BrownJACS, 1972, 94, 7159.JACS, 1935,511 , 903.MeOrg.Syn, 1925, 4, 53.HCHOCHO MeKOHOHCH 3- CHOHCHO C(CH 2OH) 4Ca(OH) 2C-OHR3BC= 0 RFR- B- CR3B, HOCH 2CH2OH / H 2O2/ NaOHJOC, 1986,51,4925.R,0R3C- B、0 -LAHIrCl4OOH4 work for ester) solvent: THF, SMe 2OHOiPrO Al(O iPr)O

43、iPrOHregioselectivity determined by reactivity.reactivity: aldketone > esterHOH.IrClJCS, 1969,1653. |l JCS, 1970,785.OHOHOH+49%NaBH 4NaBH 4/CeCl51%99%traceO_ Al(O iPr)OHgenerate acetoneopposite to Oppenauer oxidationJACS, 1978 , 100,2226.THL, 2000,41,5631.Luche Reductioninfluence of the lanthanid

44、e on the regiochemistryRi R* B- CROH2O2丁 R3cO- O- HB- O,o.R3c O- BHOCH 2CH2OHR3c B= O.H2O_R3C OH3-jC=C COHLJrr3.j. 1 C=C -C-OH(1), H 3O+ hydration：(2). Hg(OAc) 2, H 2O / NaBH 4r Hg(OAc) 2RCH C_R H 2Ooxymercuration - demercuration:RRR CH C_ R NaBHR CH C RHg Ohh ohOAcHg (OAc) 2： toxic, hard to removeH

45、 2O2： dangerous,skin whiten, metal decomposeOH(3), B 2H 6, H2O2 / OH -, H 2O3-j，CCOH OH(1), KMnO 4 / NaOH(2), OsO 4(3), H 2O2/HCO 2H(4). Na / EtOHciscistrancis + tranOHOHAnn, 1949 , 561, 165.JCS, 1946,2988, I JACS, 1945 , 67,1786,OH3-k practiceJOC, 1967 , 32,3452,HO.OHOHOHOOHOHOOMeMeOHOHOHH+ HOOBnBn

46、OOBnOBnPhCH 2-BrOBnOHOBnOOBnOBnO OMe H3O+- OBnBnOOBnOBnH h0H OLAHOBnOH OHPh3C-ClPd-CBnOOBnOBnOTrBnOOBnOHOBnOBnCrOPyBnOOTrOBnOBn OOBnOHOOHOHOHOHOHOhemiacetal chemistry:ROH 一1', 2' alcoholROBnROHOH - OHOHROHROTrROH4-aC-N4- a b c d eC-HAcOCompare nomenclature class:C-HC-NC-XC-OHC=Of g h iC=CC= NC(O)XC -C(O)XR3C_ NH 2 primarysecondarytertiaryR_ C_ NH 2R_C_NHRR_C_NR 2C-Nnot a very useful reaction(1). nit