Organic Chemistry: Oxidation Reactions and Reagents, Study Guides, Projects, Research of Stereochemistry

Download Organic Chemistry: Oxidation Reactions and Reagents and more Study Guides, Projects, Research Stereochemistry in PDF only on Docsity! OXIDATIONS 5 Oxidations Carey & Sundberg: Chapter 12 problems: 1a,c,e,g,n,o,q; 2a,b,c,f,g,j,k; 5; 9 a,c,d,e,f,l,m,n; 13 Smith: Chapter 3 March: Chapter 19 I. Metal Based Reagents 1. Chromium Reagents 2. Manganese Rgts. 3. Silver 4. Ruthenium 5. other metals II Non-Metal Based Reagents 1. Activated DMSO 2. Peroxides and Peracids 3. Oxygen/ ozone 4. others III. Epoxidations Metal Based Reagents Chromium Reagents - Cr(VI) based - exact stucture depends on solvent and pH - Mechanism: formation of chromate ester intermediate Westheimer et al. Chem Rev. 1949, 45, 419 JACS 1951, 73, 65. C R R H O Cr HO O- O- O R R + HCrO3 - + H+ + H2O H+ HCrO4 - R2CH-OH Jones Reagent (H2CrO4, H2Cr2O7, K2Cr2O7) J. Chem. Soc. 1946 39 Org. Syn. Col. Vol. V, 1973, 310. - CrO3 + H2O → H2CrO4 (aqueous solution) K2Cr2O7 + K2SO4 - Cr(VI) → Cr(III) (black) (green) - 2°- alcohols are oxidized to ketones O R Racetone Jones reagent R2CH-OH - saturated 1° alcohols are oxidized to carboxylic acids. R H O R H HO OH R OH O acetone Jones reagenthydration RCH2-OH Jones reagent acetone - Acidic media!! Not a good method for H+ sensitive groups and compounds OXIDATIONS 6 Me3Si OH SePh CO2CH3 Me3Si SePh O O H17C8 OH O O O H17C8 O O 2) CH2N2 acetone 1) Jones, acetone JACS 1982, 104, 5558 Jones JACS 1975, 97, 2870 Collins Oxidation (CrO3•2pyridine) TL 1969, 3363 - CrO3 (anhydrous) + pyridine (anhydrous) → CrO3•2pyridine↓ - 1° and 2° alcohols are oxidized to aldehydes and ketones in non-aqueous solution (CH2Cl2) without over-oxidation - Collins reagent can be prepared and isolated or generated in situ. Isolation of the reagent often leads to improved yields. - Useful for the oxidation of H+ sensitive cmpds. - not particularly basic or acidic - must use a large excess of the rgt. OH O O ArO CrO3•(C5H5N)2 CH2Cl2 JACS 1969, 91, 44318. O O O ArO H CrO3 catalyzed (1-2 mol % oxidation with NaIO6 (2.5 equiv) as the reozidant in wet aceteonitrile. oxidized primary alcohols to carboxylic acids. Tetrahedron Lett. 1998, 39, 5323. Pyridinium Chlorochromate (PCC, Corey-Suggs Oxidation) TL 1975 2647 Synthesis 1982, 245 (review) CrO3 + 6M HCl + pyridine → pyH+CrO3 Cl- ↓ - Reagent can be used in close to stoichiometric amounts w/ substrate - PCC is slighly acidic but can be buffered w/ NaOAc HO OHC OH O O CHO O O TL, 1975, 2647 PCC, CH2Cl2 JACS 1977, 99, 3864. PCC, CH2Cl2 OXIDATIONS 9 Sodium Permanganate TL 1981, 1655 - heterogeneous reaction in benzene - 1° alcohols are oxidized to acids - 2° alcohols are oxidized to ketones - multiple bonds are not oxidized Barium Permanganate (BaMnO4) TL 1978, 839. - Oxidation if 1° and 2° alcohols to aldehydes and ketones- No over oxidation - Multiple bonds are not oxidized - similar in reactivity to MnO2 Barium Manganate BCSJ 1983, 56, 914 Manganese Dioxide Review: Synthesis 1976, 65, 133 - Selective oxidation of α,β-unsatutrated (allylic, benzylic, acetylenic) alcohols. - Activity of MnO2 depends on method of preparation and choice of solvent - cis & trans allylic alcohols are oxidized at the same rate without isomerization of the double bond. OH HO HO OH O HO J. Chem. Soc. 1953, 2189 JACS 1955, 77, 4145. (62%) MnO2, CHCl3 - oxidation of 1° allylic alcohols to α,β-unsaturated esters OH CO2Me OH CO2R JACS1968, 90, 5616. 5618 MnO2, ROH, NaCN MnO2, Hexanes MeOH, NaCN Manganese (III) Acetate α-hydroxylation of enones Synthesis 1990, 1119 TL 1984 25, 5839 O Mn(OAc)3, AcOH O AcO Ruthenium Reagents Ruthenium Tetroxide - effective for the conversion of 1° alcohols to RCO2H and 2° alcohols to ketones - oxidizes multiple bonds and 1,2-diols. OXIDATIONS 10 Ph OH O Ph CO2H Ph O H CH3 OH OH Ph CO2H H CH3 JOC 1981, 46, 3936 94%ee96% ee RuO4, NaIO4 CCl4, H2O, CH3CN CCl4, H2O, CH3CN RuO4, NaIO4 O O HO O O O TL 1970, 4003 CCl4, H2O RuO2, NaIO4 Tetra-n-propylammonium Perruthenate (TPAP, nPr4N+ RuO4-) Aldrichimica Acta 1990, 23, 13. Synthesis 1994, 639 - mild oxidation of alcohols to ketones and aldehydes without over oxidation MeO2C OSiMe2tBu OH N+ O -O Me MeO2C OSiMe2tBu O TL 1989, 30, 433 TPAP (Ph3P)4RuO2Cl3 RuO2(bipy)Cl2 - oxidizes a wide range of 1°- and 2°-alcohols to aldehydes and ketones without oxidation of multiple bonds. OH OH H CHO CHO H JCS P1 1984, 681. Ba[Ru(OH)2O3] -oxidizes only the most reactive alcohols (benzylic and allylic) (Ph3P)3RuCl2 + Me3SiO-OSiMe3 - oxidation of benzylic and allylic alcohols TL 1983, 24, 2185. Silver Reagents Ag2CO3 ( Fetizon Oxidation) also Ag2CO3/celite Synthesis 1979, 401 - oxidation of only the most reactive hydroxyl O OH OH O O OH O O OH OH O O O O Ag2CO3, C6H6 JACS 1981, 103, 1864. mechanism: TL 1972, 4445. Ag2CO3 OXIDATIONS 11 - Oxidation of 2° alcohol over a 1° alcohol OH OH Ag2CO3, Celite (80%) O OH JCS,CC 1969, 1102 Silver Oxide (AgO2) - mild oxidation of aldehyde to carboxylic acids RCHO AgO2, NaOH RCO2H Ph CHO Ph CO2H AgO2 JACS 1982, 104, 5557 Prevost Reaction Ag(PhCO2)2, I2 OAcAcO OHAcOAg(PhCO2)2, I2 AcOH, H2O AcOH Ag(PhCO2)2, I2 Other Metal Based Oxidations Osmium Tetroxide OsO4 review: Chem. Rev. 1980, 80, 187. -cis hydroxylation of olefins old mechanism: O Os O O O OH OH cis stereochemistry osmate ester intermediate OsO4, NMO - use of R3N-O as a reoxidant TL 1976, 1973. OH O O OH O O OH OH R3 R4 R2 HRO HO R4 R2 HRO R3 HO H Stereoselectivity: OsO4 OsO4, NMO TL 1983, 24, 2943, 3947 OsO4, NMO OXIDATIONS 14 Sharpless Asymmetric Dihydroxylation (AD) Chem. Rev. 1994, 94, 2483. - Ligand pair are really diastereomers!! R1 N R2 R3 Ar H OR'H N Ar OR'H R1 R2 R3 OH OH N MeO acetone, H2O, MNO 0.2-0.4% OsO4 "HO OH" "HO OH" 80-95 % yield 20-80 % ee R'= p-chlorobenzoyl dihydroquinidine ester dihydroquinine ester Ar = Mechanism of AD: Second Cycle (low enantioselectivity) First Cycle (high enantioselectivity) H2O L [O] H2O, L Os O L O O O O O Os O O L O O Os O O O O O Os O O O O HO OH OH HO R3N Os O O O O O [O] - K3Fe(CN)6 as a reoxidant gives higher ee's- eliminates second cycle TL 1990, 31, 2999. - Sulfonamide effect: addition of MeSO2NH2 enhances hydrolysis of Os(VI) glycolate (accelerates reaction) - New phthalazine (PHAL) ligand's give higher ee's N O H Et N MeO N Et OMe H N NN O N O H Et N OMe N Et MeO H N N N O JOC 1992, 57, 2768. (DHQ)2-PHAL(DHQD)2-PHAL OXIDATIONS 15 - Other second generation ligands N H Et N MeO N Et OMe H N N N O O Ph Ph PYR N Et OMe H N ON O IND Proposed catalyst structure: N N O H N N Os H N N OMe O MeO O HO O O N Os N Phthalazine Floor "Bystander quinoline (side wall)Asymmetric Binding Cleft NN O O N N OMe Os O O O O N OMe N H O O Corey Model: JACS 1996, 118, 319 Enzyme like binding pocket; [3+2] addition of OsO4 to olefin. RL Rs RM H DHQL DHQ RL large and flat, i.e Aromatics work particularly well OXIDATIONS 16 R1 R1 R1 R2 R2 R1 R2 R1 R3 R2 H R1 R3 R2 R4 Olefin Preferred Ligand PYR, PHAL PHAL IND PHAL PHAL PHAL, PYR + MeSO2NH2 ee's 30 - 97 % 70 - 97 % 20 - 80 % 90 - 99.8 % 90 - 99 % 20 - 97 % "AD-mixes" commercially available pre-mix solutions of Os, ligand and reoxidant AD-mix α (DHQ)2PHAL, K3Fe(CN)6, K2CO3, K2OsO4 (0.4 MOL % Os to C=C) AD-mix β (DHQD)2PHAL, K3Fe(CN)6, K2CO3, K2OsO4 N N O O O HO N O OMe AD (DHQD)2PYR 94 % ee N O OMe OH OH N O OMe OH O Campthothecin - Kinetic resolution (not as good as Sharpless asymmetric epoxidation) Ph tBu tBu OH Ph OH H tBu OH H OHPh Ph tBu + + AD mix α 30% conversion (4 : 1) enriched tBu H Ph H tBu Ph H H olefins with axial dissymmetry OXIDATIONS 19 Corey-Kim Oxidation (DMS/NCS) JACS 1972, 94, 7586. Me S: Me Me S+ Me ClN O O Cl N-Chlorosuccinimide (NCS) + Oxygen & Ozone Singlet Oxygen Acc. Chem. Res. 1980, 13, 419 Tetrahedron 1981, 37, 1825 O O O O H O O O O H OH Tetrahedron 1981, 1825 Ph3P:"ene" reaction triplet singlet hν • •• • • • • • • •• • • •• • • • 1) O2, hν, Ph2CO 2) reduction HO Ozone Comprehensive Organic Synthesis 1991, 7, 541 O O O O O O O O OH H RCOOH Jones NaBH4 +Ph3P: -78°C O3, CH2Cl2 Other Oxidations Mukaiyama Oxidation BCSJ 1977, 50, 2773 R CH R OH R CH R O MgBr N N O N N O R O RTHF PrMgBr MeO Cl NH CH3 MeO O OEt O OH SEt SEt NO O N N O N O tBuMgBr, THF (70%) MeO Cl NH CH3 MeO O OEt O OHC SEt SEt JACS 1979, 101, 7104 OXIDATIONS 20 O OH N N O N N O O O tBuMgBr, THF Dess-Martin Periodinane JOC 1983, 48, 4155. JACS 1992, 113, 7277. - oxidation conducted in CHCl3, CH3CN or CH2Cl2 - excellent reagent for hindered alcohols - very mild O I O AcO OAc OAc R O R O I O OAc HO RO O RO JOC 1991, 56, 6264(99%) Dess-Martin + 2 AcOH+ R2CH-OH • • Chlorite Ion -oxidation of α,β-unsaturated aldehydes to α,β−unsaturated acids. Tetrahedron 1981, 37, 2091 OBn CHO OBn OBn CO2H OH H -O-Cl-O - HClO2 tBuOH, H2O NaClO2, NaH2PO4 Selenium Dioxide - Similar to singlet oxygen (allylic oxidation) OAc OAc OH 1) SeO2 2) NaBH4 Phenyl Selenium Chloride OLi O SePh O Se H O- Ph O - PhSeOHH2O2 THF PhSeCl - PhS-SPh will do similar chemistry however a sulfoxide elimination is less facile than a selenoxide elinimation. Peroxides & Peracids - R3N: → R3N-O - sulfides → sulfoxides → sulfones -Baeyer-Villiger Oxidation- oxidation of ketones to esters and lactones via oxygen insertion Organic Reactions 1993, 43, 251 Comprehensive Organic Synthesis 1991, vol 7, 671. OXIDATIONS 21 m-Chloroperbenzoic Acid, Peracetic Acid, Hydrogen peroxide Cl O O O H H NO2 O O OO2N R1 R2 O ArO HO O CR1 O H R2 O O R1 O O R2 + ArCO2H O Ar - Concerted R-migration and O-O bond breaking. No loss of stereochemistry - Migratory aptitude roughly follows the ability of the group to stabilize positive charge: 3° > 2° > benzyl = phenyl > 1° >> methyl O O O mCPBA O O O O HO HO CO2H CHO HO O CO2H OH PGE1 JACS 1971, 93, 1491 O CH3 CH3 mCPBA (80 %) O O CH3 CH3 Tetrahedron Lett. 1977, 2173 Tetrahedron Lett. 1978, 1385 Oxone (postassium peroxymonosulfate) Tetrahedron 1997, 54, 401 RCHO oxone acetone (aq) RCOOH Oxaziridines reviews: Tetrahedron 1989, 45, 5703; Chem. Rev. 1992, 92, 919 N C O R R2 R3 - hydroxylation of enolates N O PhSO2 Ph R' R O _ R' R O O Ph NSO2Ph _ R' R O HO PhSO2N=CHPh+ R' R O _ PhSO2N=CHPh+ R' R O NHSO2PhPh By-product supresed by using bulkier oxaziradine such as camphor oxaziradine R' R O Base OXIDATIONS 24 - Catalysts: VO(acac)2; Mo(CO)6; Ti(OiPr)4 - Oxidant: tBuOOH; PhC(CH3)2OOH OH VO(acac)2 tBuOOH OH O (CH2)n OH (CH2)n OH O ring size VO(acac)2 MoO2(acac)2 mCPBA 5 >99% -- 84 6 >99 98 95 7 >99 95 61 8 97 42 <1 9 91 3 <1 Acyclic Systems: Rc Rt R3 R1 R2 O ML O O L tBu A1,3-strain A1,2-strain 1,3-interaction Rc RtR3 R1 R2 O M O O L L Major influences: A1,2-Strain between Rg and R1 (Rg and R2) A1,3-strain between R2 and Rc (R1 and Rc) 1,3-interactions between L and R1 (L and R2) OH VO(acac)2, tBuOOH OH OH + OO (4 : 1) O H H H H3C O M O tBu L LO H H O M O tBu L L CH3 H OXIDATIONS 25 OH VO(acac)2, tBuOOH OH OH + OO (19 : 1) O H H CH3 H M O tBu L L O H H O M O tBu L L H3C H3C H3C O H OH VO(acac)2, tBuOOH OH OH + OO (> 99 : 1) SiMe3 SiMe3 SiMe3 - Careful conformational analysis of acyclic systems is needed. Homoallylic Systems OH OH O V O O OtBu L L dominent stereocontrol element Titanium Catalyst structure: Ti O RO O OR OR CO2R RO2C O O OR ORO O Ti OR Ti O O RO O OR OR O CO2R CO2R O O O tBu CO2R Ti O Ti O O RO O OR OR O CO2R CO2R O O O tBu CO2R Ti O FavoredDisfavored OXIDATIONS 26 Asymmetric Epoxidation tBuOOH, Ti(OiPr), (+) or (-) Diethyl Tartrate, 3Å molecular sieves Empirical Rule R1 R2 R3 OH (+)- DET epoxidation from the bottom (-)- DET epoxidation from the top Catalytic system: addition of molecular sieves to "soak" up any water with 3A sieves, 5-10 mol % catalyst is used. Preparation of Allylic Alcohols: R CHO R CO2R' R CO2R' [(CH3)2CHCH2]2AlH R OH [(CH3)2CHCH2]2AlH R OH R C C CH2OH Na (MeOCH2CH2O)2AlH2 H2, Lindlar's Catalyst (REDAL) (DIBAL) "In situ" derivatization of water soluble epoxy-alcohol OH (-)-DIPT (+)-DIPT OH OH O O (R)-glycidol (S)-glycidol water soluble OH O O O S O O NO2 organic soluble Alkoxide opening of epoxy-alcohol product reduced by use of Ti(OtBu)4 and catalytic conditions OH O R O - from Ti(OiPr)4 OH OH R O Stoicheometric vs Catalytic epoxidation: OH OH O (+)-DET Ti(OiPr)4 tBuOOH stoicheometric: 85% ee catalytic (6-7 mol %) 47% yield >95% ee in situ deriv. with PNB 78% yield 92 % ee >98 %ee after 1 recrystallization OH OH O (+)-DET Ti(OiPr)4 tBuOOH R R yields: 50 - 100 % ee: > 95%