Chemistry 206 Advanced Organic Chemistry Handout 26B Synthetic Applications of a-Diazocarbony Compounds An Evans group Afternoon Seminar Krista B. goodman January 15, 1999 Matthew d. shair Monday, November 18. 2002
Matthew D. Shair Monday, November 18, 2002 Chemistry 206 Advanced Organic Chemistry Handout 26B Synthetic Applications of -Diazocarbonyl Compounds An Evans Group Afternoon Seminar Krista B. Goodman January 15, 1999
Krista beaver Synthetic Applications of a-Diazocarbonyl Derivatives Chem 206 Synthetic Applications of a-Diazocarbonyl Compounds Synthesis of a-Diazocarbonyl Compounds An Evans Group Afternoon Seminal First synthesized by Curtius in 1883 by diazotization of a-amino acids Krista Beaver January 15, 1999 Arndt-Eistert synthesis(1927) 1.(CICO)2, DMF eading references 2. CH2N2 McKervey and Ye, Chem. Rev. 1994 1091 Dtsch. Chem Doyle, McKervey and Ye, Modern Methods for Organic Synthesis with 1 Diazo Compounds, Wiley, 1998 0c19861282 Diazocarbonyl Compounds. Structure and nomenclator see Danheiser JOC 1990 1960 azocarbonyl Diazonium Acyl Transfer insertion rearrangement Badet, JOC 1993 1641 solomys 26B-011111/017:59PM
Krista Beaver Synthetic Applications of α-Diazocarbonyl Derivatives Chem 206 Synthetic Applications of α-Diazocarbonyl Compounds An Evans Group Afternoon Seminar Krista Beaver January 15, 1999 Leading References: McKervey and Ye, Chem. Rev. 1994 1091 Doyle, McKervey and Ye, Modern Methods for Organic Synthesis with Diazo Compounds, Wiley, 1998 Diazocarbonyl Compounds: Structure and Nomenclature R' R O N N acid R' R O N N ∆, hv or M R' R O cyclopropanation insertion rearrangement ylide formation Diazocarbonyl Diazonium solvolysis rearrangement displacement Synthesis of α-Diazocarbonyl Compounds • First synthesized by Curtius in 1883 by diazotization of α-amino acids R OH O • Arndt-Eistert synthesis (1927) R O N2 1. (ClCO)2, DMF 2. CH2N2 • Diazo Transfer R O R' RSO2N3, base R O R' N2 • Acyl Transfer O O N N2 O O ROH O O R N2 Arndt and Eistert, Ber. Dtsch. Chem. Ges. 1927 60B 1122 Pettit, JOC 1986 1282 Regitz, ACIEE 1967 733 Badet, JOC 1993 1641 For temporary activation of carbonyl compounds prior to diazo transfer, see Danheiser, JOC 1990 1960 R=Me, Ts, etc. 26B-01 11/11/01 7:59 PM
Krista beaver Synthetic Applications of a-Diazocarbonyl Derivatives Chem 206 Some Reactions of a-Diazocarbonyl Compounds Acid Catalyzed Reactions of Diazo compounds H SiR3 R2R Common acids include BF3. 0Et2, HE mechanism of activation is unclear for both Lewis and protic acids: CNs SeR activation may occur by protonation on C or o Aco SeR Acid-Catalyzed Reactions TFA-20°c Mander. Chem. Comm. 1971 773 Having become familiar with the peculiarities of diazoketone chemistry while preparing [other Adapted from McKervey. Chem. Rev. 1994 1090 diazomethane. d cured to s trat we aght be able mo subst ute ae gap grs p for bromine Mander, JACS 1980 6626 26B-021220994:05PM
Krista Beaver Synthetic Applications of α-Diazocarbonyl Derivatives Chem 206 R R1 N2 O R R1 O X X R R1 O H X R R1 O H OR R R1 O R2 OR R R1 O H OTs R R1 O H OCOR2 R R1 O H O2P(OR2)2 R R1 O H SR R R1 O RS SR R R1 O R2 R3 R R1 O H SeR R R1 O R2 H R R1 O AcO SeR R R1 O CNS SeR R R1 O HO OH R R1 O H NR2R3 R R1 O H SiR3 R R1 O H BR2 R R1 O H OH R R1 O H PO(OR)2 Some Reactions of α−Diazocarbonyl Compounds Adapted from McKervey, Chem. Rev. 1994 1090 Acid Catalyzed Reactions of Diazo Compounds Review: Smith, Tet. 1981 2407 H3C CH3 O N N acid H3C CH3 O N N Diazocarbonyl Diazonium Common acids include BF3•OEt2, HBF4, TFA, etc. Mechanism of activation is unclear for both Lewis and protic acids; activation may occur by protonation on C or O Acid-Catalyzed Reactions OMe O N2 O -25°C, 2 min (82%) O TFA Gibberrellic Acid Mander, JACS 1980 6626 Cl3COCO OCOCCl3 HO O N2 TFA, -20°C (96%) O O "Having become familiar with the peculiarities of diazoketone chemistry while preparing [other compounds] (and, I might add, inured to handling uncomfortably large quantites of diazomethane), it occurred to us that we might be able to substitute a diazo group for bromine." Lewis Mander Mander, Chem. Comm. 1971 773 Tet., 1991 134 26B-02 12/20/99 4:05 PM
Krista beaver Synthetic Applications of a-Diazocarbonyl Derivatives Chem 206 More Acid Catalysis B-Ketoester synthesis Olefins as nucleophiles Roskamp, JOC 1989 3258 Yields are good when R is aliphatic: moderate when aromatic Smith's cyclopentenone annulation: Ring expansion N2 BF3 OE 2 Me COE ars ca Eto2 CCHN2 Smith.T19754225 Ghosh. Chem. Comm. 19881421 Aplysin Rearrangement Substitution: BF3OEt2 ROH, BF3. 0Et2 Mander. Aust. J. Chem. 1979 1975 Thiols also work well John and thomastl 1978 995 Polyene cyclizations Tetrahydrofuran Synthesis BnO- CCHN2 Smith. JACS 1981 2009 Diastereoselectivity increases with size of independent of Lewis acid or protecting group TL 1998 8195 26B-031220994:14PM
Krista Beaver Synthetic Applications of α-Diazocarbonyl Derivatives Chem 206 Smith, TL 1975 4225 Me Me O N2 BF3•OEt2 O Me Me (40 - 65%) O Me Me Lindlar's cat. (100%) Smith's cyclopentenone annulation: More Acid Catalysis Olefins as nucleophiles: Me O N2 Me O Me Me Cl HCl (100%) Mander Jasmone O R N2 O R O OBF3 N2 O O R BF3•OEt2 Mander, Aust. J. Chem. 1979 1975 N2 O Rearrangement: Polyene cyclizations: O Me Me O Me Me 46% 12% + Smith, JACS 1981 2009 BF3•OEt2 EtO H O N2 SnCl2 EtO O R' O Me O Me Me O Me O Me Me O CO2Et R H O BF3•OEt2 Roskamp, JOC 1989 3258 Ghosh, Chem. Comm. 1988 1421 + EtO2CCHN2 (81%) Me O Me Me Me Br Aplysin (50 - 90%) β-Ketoester synthesis: Ring expansion: Yields are good when R is aliphatic; moderate when aromatic TESO O R H BF3•OEt2 BnO2CCHN2 (53 - 87%) O R OH CO2Et Angle, TL 1998 3119 N S N2 O O O Me Me CO2CH2CCl3 H N S O O O Me Me CO2CH2CCl3 H John and ThomasTL 1978 995 ROH, BF3•OEt2 RO ">60%" Thiols also work well TL 1998 8195 Diastereoselectivity increases with size of R; independent of Lewis acid or protecting group diastereoselection 3:1 - 20:1 Substitution: Tetrahydrofuran Synthesis: 26B-03 12/20/99 4:14 PM
Krista beaver Synthetic Applications of a-Diazocarbonyl Derivatives Chem 206 Substitution reactions Base-nduced reactions Kapur and Fasel, TL 1985 3875 DA is the optimal base for lithiation Pellicciari JCS Perkins /1985 493 Synthesis of a-substituted chiral acids: Ester alkylation Displacement occurs with Ingold, Nature 1950 179 tention of stereochemistry Rapoport, JOC 1985 5223 other examples, see McKervey Reaction with boranes Seyferth, JOC 1971 1379 EtO2 CCHN2, then D2O ilbert. JOC 1982 1837 (97%,100%d) Hooz, JACS 1969 6195 OBB Mechanism? n-Buli. the (61%) Wojtkowski, JOC 1971 1790 26B-041220994:24PM
Krista Beaver Synthetic Applications of α-Diazocarbonyl Derivatives Chem 206 Substitution Reactions N S H2N O O O Me Me COOH H NaNO2, Br2 N S O O O Me Me COOH H Br Br Kapur and Fasel, TL 1985 3875 Synthesis of α-substituted chiral acids: Me COOH H2N H Me N2 H O OH O Me H O NuMe COOH Nu H Ingold, Nature 1950 179 (90%) Nu = Br, Cl, F Displacement occurs with retention of stereochemistry For other examples, see McKervey, Chem. Rev. 1994 1091 Deamination: N S O O O Me Me COOH H Mg Reaction with Boranes BH3 B 3 EtO2CCHN2, then D2O CO2Et D H (97%, 100% d1) O N2 Bu3B OBBu2 Bu n-BuLi, then MeI O Bu Me Hooz, JACS 1969 6195 Wojtkowski, JOC 1971 1790 (61%) Base-Induced Reactions R Li O N2 R O N2 R2 OH R1 R1 R2 O Pellicciari, JCS Perkins I 1985 493 Rapoport, JOC 1985 5223 N2 Li CO2Et CO2Et N2 O + O O O CO2Et O Rh2(OAc)4 100% + Aldol-type reactions: Ester alkylation: Gilbert-Seyferth Reagent: N2 (MeO)2OP H R1 R2 O KOt-Bu R1 R2 + Seyferth, JOC 1971 1379 Gilbert, JOC 1982 1837 LDA is the optimal base for lithiation HO N2 O MeO O CF3COOH O Mechanism? 26B-04 12/20/99 4:24 PM