官能团相互转化

i 5- 7- g f e d c b a e d c b a i h g f e d c b a h g f e d c b a h g f e d c b a 6- 4-3-1- 2- i h g f e d c b a C=C -C(O)-CH3 CH-CH CH-CX Functional Group Interconversion C=C C C C=C C C RCH2-SO2Ph RC CH C C C-NH2; C-NO2 C-OH C(OR)2; C(SR)2 C=C-OR; C=C-SR C C C N C=N-OH, C=N-H C=S C=O C=O C-C(O)Z C=C C=O C-OH C-X C-N C-H C-N C=O C---OH C-OC(O)R C-X C-OCH2OR C-NH2 C-OR C-H C-OH C=C C-H C(O)OR C-(OR)2 C-OH C-OR C-CHO C-CO2H C-CN C=C C=O C-S C-X C-OH C-H C=Cj C(O)X h C N j k C-H C-Br 8- C-X i C-OH C-OH C(O)Zd c b a e d c b a f C-NH2 C-H j CX-CY C C X C=O h g f i C CH RCH(CO2H)-CH3 -C(O)-CH3 O O O X CRR'=CHX j C O C-NH2 C-CN 9- C-CH3 C-Xa e C=O 1-a dry pyridine: from CaH2 and distilled (an ester) triflate mesylate tosylate S O O ORCH2 CF3 S O O ORCH2 CH3 thiocarbonate dry Py CH3 CH3 CH3 OH (2). for 3' alcohol: LiAlH4 (1). for 1', 2' alcohol: C-HC-OH 1- i h g f e d c b a C-CHO C-CO2H C-CN C=C C=O C-S C-NH2 C-X C-OH C-H O C S O Ph SnBu3 CH3 CH3 CH3 Hn-Bu3SnHC S O PhCl O C S O Ph RCH2-H CH3S O O ORCH2 CH3 S O O Cl RCH2OH steric OK purification textbook ~ $ 30 / Kg toluenesulfonyl chloride (s) methanesulfonyy chloride (l) ~ $ 30 / Kg j C(O)X Ph2SiHCl / InCl3 Ph Ph H Ph OH Ph JOC, 2001, 66, 7741. ii. Ph2SiHCl / InCl3 i. p-TsCl // LiAlH4 i. ClC(S)OPh // n-Bu3SnH Ph Ph O Cl2In Cl SiPh2 Hvia: via: a unique Lewis acid catalyst, acceleratedeoxgyenation InCl3 indium trichloride ii. Et3SiH / Lewis acid J. Org. Chem. 2000, 65, 6179 JOC, 2000, 65, 6179. CHCl2 rt, 3 hr 1-b Bu3SnH: (l), easy to remove Ph3SnH: (s), hard to remove Me3SnH: too volatile, toxic (AIBN) N N CN CN - N2 CN azobisisobutyronitrile n-BuSnH n-BuSn Br R n-BuSnBr R H R unstable in acid, form H2 gas; stable in weak baseNaBH3CN: stable at pH 5-6 hygroscopic, dried self, suggest: buy small amount each time (Grignard reagent) H2OMg / Et2O JOC, 1969, 34, 3923. HBr Na / NH3; Li / NH3; Na / EtOH Zn; Fe; Sn; Mg (3). metal reduction (2). hydride reduction (1). free radical reduction JACS, 1972, 94, 8905. C-HC-X AIBN n-Bu3SnH HBr radical initiator NaBH4 / InCl3 / CH3CN radical reagent n-Bu3SnH / AlBN JACS, 2002, 124, 906. i iii NaBH3CN i LiAlH4 i ii ii NaBH4 ii THL, 1969, 3095. JOC, 1976, 41, 3064.iv LiBHEt3 (super hydride) n-BuSnH n-BuSn mechanism uncertain, probably radical burn filter paper if dry Raney Nickel: Ni - Al alloy, suspension tosylimide tosylamide JCS Perkin Trans I, 1973, 654. (3). LiAlH4 / CuCl2 NaBH4 / NiCl2 NaBHEt3 / FeCl2 (or CoCl2, VCl3) (2). Li / NH3 (1). Raney Ni N SO2Ar SO2Ar RCH2 RCH2N SO2Ar - BuH RCH2NH SO2Ar BuLi LiAlH4 RCH2-H CH3 S O O Cl RCH2NH2 BuLi 1-d 1-c C-HC-S LiAlH4 C-HC-NH2 RCH2-HRCH2NH2 Hinsberg's test radical mechanism weaker C-N bond Chemistry: R-SH R-S-R R2SO R2SO2 R-SS-R remove: Hg+; Ni (1). (2). Ar-H NaNO2 HCl H3PO2 Ar-NH2 RCH2NH2 RCH2NMe3 R=CH2 R-CH3(4). X- RCH2NMe3 OH- Ag2O JOC, 1985, 50, 427. p-TsCl NaH NaHp-TsCl NH2Cl via: N NH2 SO2Ar Ar NaH N NHAr N NAr Ar-H - ArSO2H (3). Ar-NH2 Ar-H p-TsCl JOC, 2001, 66, 8293. ArSO2Cl Raney Ni NHN SMeO2C CH2Ph EtO2C O NHN HMeO2C CH2Ph EtO2C for acyclic, may C=C side product basic neutral acidic H H H- N N Ts CH2Cl2 C=O C-H1-e (1). Clemmensen reduction: Zn-Hg / HCl (2). thioketal: (3). Wolff-Kishner reduction: (5). Tosylhydrazone reduction (Shapiro reaction): (modified Wolff-Kishner reduction):) (6). enol derivatives: SH SH / BF3, CH2Cl2 // RaNi N2H4, OH-, heat TsNHNH2 // RED limit: for α-H compd. H H Ra(Ni) BF3, S S H HS SH H O thioketal: inert to LAH; react with RaNi; smell terrible and stay long; discard shoses thioketal major side-product: drawback of the reaction N N - N2 OH- HNN HN N HOH- N NH2 N2H4 O H H N C H C O CF3 S O O O S O CF3 O C C OTf H2 PtO2 C C H H H Tf2O / N // H2 / PtO2 LAH, NaBH4: 2 group compete at Stanford U. B2H6: very flamable, fire if shoot out from syringe O O B H best suitable for aryl ketone (ArCOR); not good for conjugate ketone preparation: HgCl2 into Zn RED choice: MeLi; NaBH3CN (good) PtO2 + H2 = Pt OH O C6H13 similar: Sn / HCl (4). Pd-C / HCO2NH4: mild, efficient Ph Ph O Ph Ph Synthesis, 2001, 16, 2370. HCO2NH4 Pd-C (7). Et3SiH / CF3COOH Ph O NO2 PhNO2 JOC, 1973, 38, 2675. CF3COOH Et3SiH HO OHH H PtO2 H2 HO OH $ 50 / 25 g JOC, 1993, 58, 4979. syn-addition prepare isotope CH3CO2D H D C=C C-C-H1-f (1). H2 / cat (2). HN=NH (diimide) (3). B2H6 // RCO2H, heat Wilkinson's catalyst: regioselective, prefer isolated double bond soluble in org solvent, 9 Ph group stereoselcetive: same side as OH (due to H bond) catalyst: Pd-C PtO2 Rh-C; Rh-Al2O3; RhCl(PPh3)3 Ni O O RhCl(PPh3)3 N2H2: unstable; generated in situ from "DEAD" (diethyl azodicarboxylate) or from: N2H4 + H2O2; N2H4 + Cu(II) + O2; NH2OH + NH2OSO3 via: H B R R N N CO2EtEtO2C N N CO2HHO2C OH- - 2 CO2 N N O O H O OH N N HH - N2 C C R R R R C C R R R R H H JCS, PT1, 1986, 546. O O CO2Me O O CO2Me RhCl(PPh3)3 12 hr JACS, 1979, 101, 7020. N R N R H2 , PtO2 TFA , 60 ℃ R = NHAc , NH2 JOC, 2002, 67, 7890. in acetic condition benzene (4). n-Bu2SnI / MgBr2-Et2O // H3O+ OEt O H3O+ OEt O MgBr2-Et2O n-Bu2SnI JOC, 2001, 66, 8690. O SnH OEtI RR O OEt SnI RH R via: not radical mech. pyridinium betaine solvent N Ph PhPh R R H N Ph PhPh R R CO2 - CO2 b.p. ~ 230 C highly toxic, cancer suspected agent? = HMPT: hexamethylphosphoric triamide (Me2N)3P=O toxic? characteristcs: IR, CMR which is δ+ ? C CR Nnot quite same: not for H - e- CO2H CO2H (3). organic electrochemistry β-CO2(1). particular structure: C-H1-g (1). K / Al2O3 K / HMPA (2). Na / NH3 1-h (2). normal structure: SOCl2 // PhSeH // n-Bu3SnH C C N JOC, 1980, 45, 3227 CN: ~ X (pseudo halogen), form KCN, NaCN with IA elements HMPA: hexamethylphosphoramide (Me2N)3P=O yes for white mouse, uncertain for human modified to: N N O C CO2H C-H C O SePhRCH2 RCH2 HC O OHRCH2 C O ClRCH2 PhSeH n-Bu3SnHSOCl2 (radical mechanism?) other Cl sources: PCl5; (COCl)2 oxalyl chloride organoselenium chemistry O H OR O 1-i CHO C-H (1). RhCl(PPh3)3 (Wilkinson's cat) (2). Rh(DPPD)2+ Cl- oxidative addition rearrangement reductive elimination Rh PPh3 PPh3C Cl O +R HRh PPh3 PPh3C R O Cl H Rh PPh3 PPh3Cl H R C O R C O H Rh PPh3 PPh3 Cl - PPh3 Cl Rh PPh3 PPh3PPh3 DPPD = Ph2P-CH2CH2-PPh2 1-j C(O)X -CH3 R Cl O R CH3HSiEt3 / B(C6F5)3 JOC, 2001, 66, 1672. O O O OH AlCl3 LiAlH4 activator / hydride source HOCH3HCl OCH3OCH3 OCH3 RCH2 OR O O R R OR OR RCH2 OCH2CH2OH (3). AlCl3 / LiAlH4 (2). HCl / NaBH3(CN) (1). hν / HSiCl3 RC-(OR)2 RC-OR2-b Si Ph Ph Cl Si CH3 CH3 Cl CH3 Si CH3 CH3 Cl N N H / TBDMS-Cl TBDPS-Cl Et3N / TMS-Cl acid: H2SO4 H3PO4 BF3-Et2O RC-OCH2CH=CH2 RC-OCPh3 = RC-OTr RC-OtBu RC-OCH3 RC-OSiR3 RC-OCH2Ph = RC-OBZl = RC-OBn i. Willianson synthesis OK: Si - Cl bond long ii. stability of silyl in acid/base: RC-O-TBDPS > RC-O-TBDMS >> RC-O-TBS iii. abbrev.: TBDMS = tert-butyl-dimethylsilyl = TBS = Silyl group: (RO-Tr) Trityl group: (tirphenylmethyl) i. SN1 reaction ii. abbreviation: triphenylmethyl = trityl = -CPh3 = -Tr iii. advantage: high MW, easy to handle (small amount become large amount) baseBr Willianson synthesis (base, SN2) not work: elimination side-product with base t-Butyl group: i. abbreviation: benzyl = PhCH2 = Bzl = Bn ii. deprotecting: H2 / Pd-C PhCH2-Cl PhCH2-Br: reactivity good PhCH2-I: reactivity better than PhCH2Br, generated in situ, PhCH2Br + NaI PhCH2-X: Benzyl- group: i. Williamson ether synthesis, SN2 type ii. not a good protecting group, too stable to convert back to alcohol Me group: CH3-X: CH3I; CH3OSO2R; (CH3)3O+ BF4-, (CH3)2SO4 base: NaH, n-BuLi, Ag2O (4). t-Bu: acid cat / (3). allyl: base / Br (6). silyl: Et3N / R3SiCl (5). trityl: py // Ph3C-Br (2). PhCH2-: base / PhCH2-X application: for protecting group e d c b a2- RC=C RC-H RC(O)OR RC-(OR)2 RC-OH RC-OR RC-OH RC-OR (1). Me: base / CH3-X 2-a (7). acetal / ketal: (see 3e) f RC-CN generate H2, or butane gas JOC, 1988, 53, 2985. trimethyloxonium tetrafluoroborate JCS, 1930, 2166. (8). ArF / CsF ROH F NO2 RO NO2 aromatic substitution reaction usually contain NO2, F as leaving group CsF see mech-13 hv I2 / Pb(OAc)4 OOH O I HO HOI limit: for 5~6 ring neighboring OH group (1). I2 / Pb(OAc)4 / hv radical mechanism: SiCl3 t-BuO RaNi with C=S JOC, 1983, 48, 1127. JOC, 1974, 39, 2470. RaNiLawesson reagent S O O O O ~ P4S10 tBu-OO-tBu HCl OO O R C O OR 2-c RC-OR 2-d RC-ORRC-H (1). hv / HSiCl3 (2). HCl / tBu-OO-tBu (3). Lawesson reagent / RaNi (4). BF3 / NaBH4 P S P SS S OCH3 CH3O O OO O Ar Ar O O Ar Ar BF3 NaBH4Lawesson reagent (2). Organoelectro Chemistry: e- / Pt, R4NOTs N OH Ph N O Ph e / Pt R4NOTs (79 %) N OH Ph R'R'MgBr Angew Chem Int Eng., 1964, 8, 525. limit for: lactone H N N H NH2O H H H N N H NH2O OCH3 NCS (3). NCS / MeOH MeOH JOC, 2002, 67, 4498. limit: for allylic alcohol C-C-OR2-e C C C C O NaBH4 OEt CO2Et OH CO2Et HHO H HO HO O i. Hg(OCOCF3)2, ROH // NaBH4 i. peracid ii. via halohydrin: HOBr, H2O // K2CO3 iii. Sharpless asymmetric epoxidation: t-BuOOH, Ti(OiPr)4 // (+)-diethyl tartrate Hg(O C O CF3)2 O O mCPBA H2O HOBr Br Br OHtrans-diaxial attack! O limit for allyl alcohol, high e.e. Sharpless stereoselective racemic products Hg O+ C O CF3 racemic products HOBr generation: NBS + H2O + DMSO O O conversion: HOAc OH OAc OSO2Me OAc EtOHC=C-OR C=C-OR C-C-ORC C C C C C C C O 2-e.1 2-e.2 2-e.3 ii. HCHO Prins Rxn OSO2Me OH O O OH OHOH HCHO (aq) O Ovia: H2O HCHO Synthesis, 1980, 871. CO3H CO3H Cl CF3CO3H CO3H CO2H good result peroxybenzoic acid MCPBA (m-chloroperoxybenzoic acid) stable solid, 85 % (contain MCBA) for safety peracid: iv. t-BuOOH, Mo(CO)6 v. KHSO5 vi. H2O2, t-BuOH, MnSO4 // NaHCO3, pH 8 JACS, 2001, 123, 2933. HO2C HO2C O new, cheap,, simple, green chemistry potassium hydrogen preoxide convenient, inexpensive, powerful. JOC, 1980, 45, 4758. JOC, 1982, 47, 2670. O OH O O Br2 via: Br2 / ROH O O Br H Heterocyclic Chem, 1990, 27, 583. C-C-OR2-f C NC ROH / HCl Et C N Et C OEt OEt OEt EtOH HCl JACS, 1942, 64, 1825. (+)-diethyl tartrate chiral source JOC, 2001, 66, 521. C-OH C-H C-OR C-NH2 C-X 3- a b c d 3-a C-OHC-H OH (1). [PhI(OAc)-O]2-Mn(TPP) (2). organic electrochemistry [PhI(OAc)-O]2-Mn(TPP) JACS, 1983, 105, 3515. JACS, 1983, 105, 2920. NO2 NH2 OH e- H2O (3). X2 / hv // OH- indirect H OH O H O OH H OH 3-a.1 3-a.2 3-a.3 H R O Se O R OH Se HO O R Se OH R OH Se(OH)2 H2O R H R OH SeO2 JACS, 1972, 94, 7154. SeO2 for allyl H: (1) Me3SiCl // MPCBA//H3O+ (2). O2, LDA, (EtO)3P RO CO2R RO CO2R OH O O RO RO O P OEt OEt via: JACS, 1975, 97, 6909. Ph O Ph OSiMe3 O Ph OSiMe3 Ph OSiMe3 OH OH Ph O OH 1. Me3SiCl MCPBA JOC, 1975, 40, 3427. H3O O2, LDA, (EtO)3P Ph O Ph O OH 2. MCPBA Me3SiCl i h g f e C=O C---OH C-OC(O)R C-OCH2OR C=Cj C O (1). Me: application: deprotecting (2). PhCH2- (5). trityl: (6). silyl: (3). allyl: (4). t-Bu: RC-OCH2Ph = RC-OBZl = RC-OBn RC-OSiR3 RC-OCH3 RC-OtBu RC-OCPh3 = RC-OTr RC-OCH2CH=CH2 C-OHC-OR N i. TMSI ii. BF3-Et2O // R-SH (or HS-CH2CH2-SH) iii. BBr3 / CH2Cl2, 0-10 C / LiI, heatvi. RCH2-OHRCH2-O-SiMe3 Me3Si-I RCH2 O CH3 SiMe3 - CH3I RCH2-O-CH3 I- - I- RCH2-O-CH3 RCH2 O CH3 BF3BF3 - RSCH3 RSH RCH2-OH OCH3 OH + heat - CH3Cl i. H2 / Pd-C ii. CN CN Cl Cl O O , OH- [O] OH - toluene OH- OH O C OCH3 O O CH2 OCH3 H2 / Pd-CO CH2 RhCl(PPh3)3, H3O+ - EtCHO - Ph3C O H HOAc H OH H O CPh3 - Me3C CF3CO2H OHO H3O+ RhCl(PPh3)3 H OHH OH Oi. TFA (CF3CO2H) ii. HBr / HOAc iii. TMS-I i. HOAc: weak acid: good leaving group ii. H2 / Pd-C: reserve, too strong, might affect other group need stronger acid i. F- : HF, Py-H+ F-; n-Bu4N+ F- ii . mild base: not for TBDPS iii. mild acid: only for TMS, not for TBDMS, TBDPS -SiMe3 -SiBuMe2 -SiBuPh2 Si - F: 140 Kcal/mol if HOBr: OK for TMDMS JOC, 1987, 52, 4973. OCOCF3 + JOC, 1973, 38, 3224. iv. AlCl3 / RSH THL, 2001, 42, 9207. MeO CO2Me HO CO2Me CH3(CH2)11 SHodorless AlCl3 v. / heatCl-N H 3-b N H Cl- triphenylmethyl organic base: TMG OR CH3CN NH NN OH R = TBDMS, TBDPS, Ac TMG 1h 1,1,3,3-Tetramethylguanidine TMG:Organic Letters, 2003, 5, 209. 3-c (1). HNO2 // H3O+ C-OHC-X (1). OH- (2). KO2 / DMSO 3-d C-OHC-NH2 not practically useful: R-OH cheaper than R-X JOC, 1975, 40, 1678. (2). Na2[Fe(CN)5(NO)] / K2CO3 / H2O NO+ H3O+ OHN2+X-NH2 3-e R-OHR-OC(O)R (1). Symmetry: ketal: use H3O+ acetal: use H3O+ (2). unsymetry: RO-MOM RO-MEM RO-MTM RO-THP MeOH+ H3O+ O H H OMe OMe + OHHO H3O+ O O O i. H3O+; ii. HCl / MeOH; iii. BBrMe2 p-TsOH / MeOH i. H3O+; ii. ZnBr2 / CH2Cl2; iii. BBrMe2 HgCl2 / CH3CN (aq.) actually, acetal exchange rather than hydrolysis H3O+ RO-H RO-H RO-H RO-H RO-CH2SCH3 RO-CH2OCH3 R O O SO3H O CH3OCH2Cl CH3OCH2CH2OCH2Cl CH3SCH2Cl p-TSOH O p-TSOH CSA (camphorsulfonic acid) (p-toluenesulfonic acid) SO3HCH3 or CSA RO-MOM highly toxic, world top 10 killer, discard not toxic not dangerous THP: tetrahydropyran RO-CH2OCH2CH2OCH3 JOC, 1984, 49, 3912. (3). Ag2O / H2O H3O+ H3O+ H3O+ THL, 1975, 3183. JOC, 1986, 51, 3913.RO2C (CH2)3CHR NH2 RO2C (CH2)3CHR OHNa2[Fe(CN)5(NO)] K2CO3 / H2O 3-f (1). base: KHCO3 (or K2CO3, NH3) / MeOH; NaOH (1 %, or 0.5 N) (3). RED: (2). acid: H3O+ PPh3 / DEAD / RCO2H // OH- 3-g R' C O R O R OH C OH C OH Mitsunobu inversion Synthesis, 1981, 1. JOC, 1987, 52, 4235. common esters: formate = HCO2R ------------------------ KHCO3 (or K2CO3, or NH3) / MeOH trifluoroacetate = CF3CO2R ------------ KHCO3 (or K2CO3, or NH3) / MeOH acetate = CH3CO2R = ROAc --------- KHCO3 (or K2CO3, or NH3) / MeOH benzoate = PhCO2R = ROBz -------- NaOH (1 %) / MeOH pivalate = tBu-CO2R = ROPv ------ NaOH (0.5 N) / EtOH (or K2CO3 / MeOH) MeOH MeOH P-TsOH LAH HCl O O OH O O HO HO OH O O O O selectivity: PPh3 / DEAD R-O-H ** * PhCO2HN NH CO2EtEtO2C PPh O R Ph Ph OH - Ph C OR O HO PhCO2H * *HO PPh3 N NH CO2EtEtO2C PPh3 ROHEtO2C N N CO2Et i LiAlH4 ii. NaAlH2(OCH2CH2OCH3) CH3O2C CO2CH3 HO OH NaAlH2(OCH2CH2OCH3)2 C6H6, r.t. hydride: electron: Na / NH3 AGIEE, 2002, 41, 3028. regioselectivity determined by reactivity. reactivity: ald > ketone > ester generate acetone opposite to Oppenauer oxidation JCS, 1969, 1653. JCS, 1970, 785. JACS, 1972, 94, 7159. O IrCl4 Al(OiPr)3 O + Al OiPr OiPr O H LAHO O O OH H H O Al(OiPr)2 IrCl3 OH H OH H OH LAH ------------ almost all: ald, ketone, acie, ester, acyl X, anhydride NaBH4 --------------- not for acid, ester (but LiBH4 work for ester) B2H6 --------------- not for ester, acyl X, anhydride; from top: LiAlH4; NaBH4; Na / NH3 Al (OiPr)3 / iPrOH ----------- Meerwein-Pondorf-Verley rxn IrCl4 / iPrOH / P(OMe)3 ------ Henbest rxn LiBH(secBu)3 ------------------ H. C. Brown from bottom: C OHC O (2). stereoselective: (1). regioselective: 3-h (3). HCHO reagent: Me CHO Me OH HCHO KOH JACS, 1935, 511, 903. CH3 CHO C(CH2OH)4 HCHO Ca(OH)2 Org.Syn, 1925, 4, 53. HCHO / KOH HCHO / Ca(OH)2 Synthesis, 1994, 1007. Ph NO2 O Ph NO2 H OH BH3 / SMe2 JOC, 2001, 66, 7514. JOC, 2003, 68, 2030. O OHBH3 / THF reflux 5 d 99.5 % trans solvent: THF, SMe2 C OHC O3-i R3B, HOCH2CH2OH // H2O2 // NaOH JOC, 1986, 51, 4925. C O R B C O R R R3B B C R R R O R B C O R R R3C B O HOCH2CH2OH R3C B O O H2O2 OH R3C B O O O O H O B O O R3C H2O R3C OH O OH OH NaBH4 / CeCl3 NaBH4 + 99% trace 51% 49% [H] JACS, 1978, 100, 2226. Luche Reduction THL, 2000, 41, 5631. influence of the lanthanide on the regiochemistry practi ce 3-k O OH OH OH OH O OH OH OH OH OH Pd-C H+ O OH OH OH OH O OH OH OH OH OH H2 Py CrO3Ph3C-Cl OH OTr OBn OBn BnO OBn LAH H3O+ OH OH OBn OBn BnO OBn PhCH2-Br O HO OBn OBn BnO OBn H O OH BnO OBn OBn OBn O OMe OBn OBn BnO OBn MeOH O OMe OH OH HO OH O OH OH OH HO OH chemistry: hemiacetal ROH ROBn ROH ROH ROTr ROH JOC, 1967, 32, 3452. 1', 2' alcohol O OTr OBn OBn BnO OBn H2O2: dangerous, skin whiten, metal decompose Hg (OAc)2: toxic, hard to remove H2O OHOBR2 OH - (40%-60%)H2O2H B H B B2H6 NaBH4 H2O Hg(OAc)2 CH C R RR H OH CH C R R OH R Hg OAc RCH C R RC OHC C (3). B2H6, H2O2 / OH-, H2O (2). Hg(OAc)2, H2O // NaBH4 (1). H3O+ 3-j O O H B R R C OHC C3-j.1 C C3-j.2 hydroboration: oxymercuration - demercuration: hydration: C C OHOH (1). KMnO4 / NaOH (2). OsO4 (3). H2O2/HCO2H (4). Na / EtOH OH OH OH OH cis tran cis + tran JACS, 1945, 67, 1786. Ann, 1949, 561, 165. JCS, 1946, 2988.cis N CH3 Cl H N CH3 Cl H Me2N N N CH3 HCl N CH3 H H hν N CH3 HH N CH3 Cl HH+NCS N CH3 ClNHCH3NHCHO Me2N N TsO C NHCHO TsO DMF Me2NH H COOH AcO HOAc TsCl MeOH K2CO3 NHCHO 2. H2 / Pt 1. LAH R3C NH2 R C NR2R C NR2 R C NHR R3C OH R2C OH RC OHR C NH2 tertiary secondary primary Compare nomenclature class: not a very useful reaction C-N C-H C-N C-X C-OH C=O C=C4- a b c d e f g 4-a C-NC-H (1). nitrene insertion process: PhI(OAc)2 / Fe (TPP)Cl (3). nitrogen cation radical (via Hofmann - Loeffler - Freytag) SO2NH2 Ph I OAc OAc S O O NH S O O N I Ph Fe (TPP)Cl S O O NH2 (insertion) TPP NN NN Ph H COOH AcO NH2 Me2N Me2N N NCS H2SO4 hν JACS, 1959, 81, 5209. 2. NaN3 C O N N N N C O 1. SO2Cl2 HOAc H2O N C O OH CO2 NH2 CH3 C O C H O O h i C N (2). PhI=NTs NHTsPhI NTs Ru cat JOC, 2000, 65, 7858. C(O)X C-C(O)X RC N Z RC NH2 NH2 NH2 RC NO2 RC N3 RC N Me RC N CPh RC N CPh3 RC NH2 RC NH2 RC NH2 RC NH2 RC NH2 i ii iii RC N C O OtBu RC N C O OPh RC NH2 RC NH2 C-N C-NH24-b CF3CO3H // Fe / HOAc 1. many reducing agents 1. NaBH4; 2. Al (Hg) H2O2 // Ac2O, heat / H3O+ H2 / Pd-C 1. HOAc; 2. H2 / Pd-C 1. TFA; 2. HCl H2 / Pd-C NH2 NH2 NO2 H - - H NO2 N O O + H NH2 NH2 CF3CO3H Fe/HOAc special case, limit for axial to equitorial NH2 - HCHO N HN OH NAc2O R C H H N N N + H R C H H NH N N RCH2 NH2 N2 N CH3 N H N CH3 N CH3 O 1. H2O2 2. Ac2O 3. H2O N HO O H2 / Pd-C NH CH2Ph NH2 N CH2 OCH3 NH TFA NH2 NH2 O C O O N C Ph CN(CH3)3C N H C O OtBu NH2 Cl C O O CH2Ph BOC ON N H C O OCPh NH C O OH NH2H2/cat CO2 4-b.1 4-b.2 [BOC-OFF] THL, 1975, 4393. BOC-ON [58632-95-4]: 2-(t-butoxycarbonyloxyimino)-2-phenylacetonitrile $ 300 / 100 g NH-BOC CO2Et NH2 CO2Et BOC-ON N-oxide application: . D -α-amino acid CO2H NH2R HH R N3 CO2EtNaN3 - TPP BF4- N Ph PhPh H R CO2Et L -α-amino acid H R CO2H NH2 1. reduction 2. hydrolysis (SN2) 2. organic electrochemistry 1. 2. 3. 4. Fe3(CO)12 / CH3OH JOC, 1972, 37, 930. NO2 NH2 Fe3(CO)12 / CH3OH reflux 8 hr NaBH4 / Pd-C Na2S Sn / HCl Vogel's 12.57 Vogel's 12.58 Vogel's 12.59 NO2 OCH3 NH2 OCH3 Eg-Ni DMF rt. 15 hr JOC, 1999, 64, 2301. Eg-Ni: electrogenerated nickel C NH2 C NH2 5. H2 / Pt (S)-C JACS, 1965, 87, 2767.sulfided platium not affect: aromatic rings, ketones, halides, nitriles, amide, easters HC(OEt)3 becomes HCO2Et new: p-TsOH / HC(OEt)3 / EtOH, reflux 5 hr CH3COCH3 O O O O OEt OEt CO2Et H H OH HO CO2