Baran Group Meeting Chemische Berichte 1960 Niklas Schöne Origin of Papers Li/Hg – very most paper from Germany, from recognised Universities and Ni(CO)4 Cl recognized Professors 50 % Cl nearly – but also from Ahmadabad, Patna (India), Tokyo (Japan), Bucharest quant. (Romania), Warsaw (Poland), Sao Paulo (Brazil) – not from the US 1. O 3 1. O3 2. H , MeOH, Main Topics 2 2. H2, MeOH, Pd/CaCO 3 Pd/CaCO3 – sugars, lignin structural evidence: – all kinds of standard heterocycle syntheses with N, S – IR-spectra – steroids (no total syntheses) MeOC – UV-spectra – Stetter: Adamantane Chemistry MeOC COMe – elemental analyses O O COMe – melting point O Miscellaneous – NMR spectra O – reactions done on a very big scale (big apparati) Criegee: Chem. Ber. 1960, 93, 1553. – chiral products are derived from chiral starting material (no total synthesis) – paper chromatography to purify compounds AcOH/H+ OAc preparatively + HO CH2O AcO OAc Important Names and their Chemistry – p. 689: Criegee: First Isolation of a primary ozonide natural product synthesis 1. MeOH/HCl, !, 97 % – p. 775: Rosenmund: Contribution to the structure of strychnine 2. PhCHO, H+, 60 % – p. 809: Alder: Diels-Alder-reactions – p. 909: Hünig: acylation of 1-Morpholino cyclopentene Ph Ph – p. 1206: Bredereck: amendment of the structure of a purine base 1. TsCl O O – p. 1374: Treibs: allylic oxidation with Hg(OAc)2 in AcOH O O 2. NaI, 83 % 3. PPh , 88 % HO Ph3P 3 4. BuLi excess (CH2)n (CH2)n base (CH2)n structural evidence: HN Me N Me CHO – IR-spectra N 1. H Me – UV-spectra Cl 2. p-TsOH, MeOH, H2O 3. Ac2O AcO base: PhLi or NaNEt2 or NaNH2 or NaH yield: 88 % (n=2), 50 % (n=3), 67 % (n=5) OAc Centaur X Huisgen: Aryne chemistry: Chem. Ber. 1960, 93, 1496. Bohlmann: Chem. Ber. 1960, 93, 1945. 2 Baran Group Meeting Chemische Berichte 1960 Niklas Schöne Improvement of the Natural product synthesis of Khellin: Preparation of 1,3-dicarbonyl compounds: O O O O O 1. ClCH CO H – CO, –HBr 2 2 + Br POCl3 R'' Br Br R'' HO OH CCl4 O Ac O O R' OH 2. CaCO3 OH 2 R' OH NaOAc ROH – HBr AcOH Treibs: Chem. Ber. 1960, 93, 551. RNH2 AcO – HBr H2, PtO2, EtOAc, 90 % O O O O O OAc O OAc RO R'' RHN R'' OAc OAc R' R' Cl CO2Me CCl4 + N2 Dioxan Me acetone 15 % 35 % a) MeOH, K2CO3, acetone, b) EtOH, aq. NaOH, 82 % methyl ethyl ketone 17 % – cyclopentanone 22 % 55 % cyclohexanone 15 % 42 % HO C O 2 cycloheptanone (suberone) 10 % – 1. AcCl, HClO4, 85 % O O 2. aq. HBr, 94 % O O R'' R'' O OH H2O, HClO4 + H2O2 ON(SO K) R''' HO C 3 2 2 DMF/H O R' O R''' R' O H 2 O O buffer, 75 % ClO4 ClO4 H OMe O O O Balaban: Chem. Ber. 1960, 93, 599. – H2O 1. SO2, EtOH, 91 % O 2. Me SO , acetone O 2 4 O O R'' 70 % R'' R'' OMe O H R''' – H+ Khellin R''' R''' O O 48 % R' O R' O Dann: Chem. Ber. 1960, 93, 2829. R' O O Baran Group Meeting Chemische Berichte 1965 Niklas Schöne Origin of Papers Recovering tertiary Phosphines from their Oxides with Silanes: – most paper again from Germany R PO + Ph3SiH R3P + Ph SiOH – but also from Budapest (Hungary), Cluj (Romania), Sofia (Bulgaria), 3 3 + Ph3SiH Helsinki (Finland), Sao Paulo (Brazil), Rajasthan (India), Brussels H2 + Ph Si O SiPh (Belgium), Strasbourg (France), Tempe (Arizona, USA!!!), Stanford 3 3 (California, USA!!!), but both articles from German postdocs! :-) R3PO + Cl3SiH R3P + Cl3SiOH Main Topics – a little more inorganic chemistry: metal carbonyls, sandwich H2 " + SiCl4 HCl + (Cl2Si–O–)n ! complexes Cl3SiH – still all kinds of aromatic compounds, especially heterocycles Et3N – still sugars and steroids (no total synthesis) Et3N-method: yield: – dyes Ph3P 85 % Et3NHCl ! – Isolation of natural products and evidence of structure (p-MeO-C6H4)3P 65 % – Synthesis of peptides (with special protecting groups) and (C6H11)3P 75 % Fritzsche: Chem. Ber. 1965, 98, 171. nucleotides (n-C4H9)3P 93 % Miscellaneous A Very Special Cycloaddition: – once tlc plates were printed for the control of a column chromatography O O O – in some cases still the same names and the same chemistry as in h# 1960 O + + Benzophenone O O Important Names and their Chemistry O 50 % O ~ 9 % – p. 451: Wittig: Question of Intermediary Appearance of Cyclobutyne O – p. 516: Beckmann: A New Ring Opening Reaction in the Bicyclo- Tetracyclooctane is not reacting with O3 or OsO4. [2.2.1] heptane series H – p. 650: Eistert: Convenient Synthesis of Cycloundecanon – p. 1081: Bredereck/Effenberger: Heterocycle synthesis CO2Me 300 ºC CO2Me – p. 1138: Huisgen: Click-Chemistry – p. 1246: Horner: New Mono- and Dihydronaphthochinones CO2Me CO2Me – p. 2221: Schöllkopf: Synthesis of Alkoxycyclopropanes Probably NOT a stepwise cyclo- – p. 2339: Criegee/Seebach: Valence Isomerizations of Cyclobutenes The following structure was not found as shown by spectral data: addition, because the author – p. 2701: Vögtle: Valence Isomerisations of double Schiff bases of didn't find intermediates like: 1,2-diamines O O – p. 2906: Schill: synthesis of catena compounds – p. 3170: Wanzlick: formation and reactivity of Bis[1,3-diphenyl- imidazolidin-2-ylidenes] O O – p. 3854: Schenk: four-membered ring synthesis through photo cyclo Askani: Chem. Ber. 1965, 98, 3618. addition of maleinic anhydrate and halogenated olefins O O Baran Group Meeting Chemische Berichte 1965 Niklas Schöne (Total) Synthesis of Retamin H H H NC Br N N N BrCN Me3N NC Cyclic Diazo Compounds: N N N N Br H N N N H H N CHCl EtOH/ 3 acetone Very different in physical and Diazomethane Diazirine 7.32 g Lupanine often in chemical properties, but: both want to get rid of N2. O 6.8 g 8 g 1. MeOH/HCl Maybe with the loss of N2 the linear diazo compound is formed transiently. 2. basic ion Bohlmann/Winterfeld: MeOH/NH3, – 15 ºC H Chem. Ber. 1965, 98, 653. exchange resin O N N H2NOSO3H, 45 % AgNO , H O, aq. column filtration NH 3 2 N 3. 160 ºC, vacuum 1. O3, CHCl3, OH aq. H SO , – H NNH NaOH (Ag2O) CO Bn 2 4 2 2 OH OH 2 –58 ºC, 34 % CO2Bn PhNO2 ! HO CN ClCO2Bn NH N N 2. KCN, MeOH, dioxane/H2O Schmitz: Chem. Ber. 1965, 98, 2509. O + + AcOH, 95 % Na2CO3 97 % 2.7 g OH 1. aq. HCl, reflux OH O 5 % 21 % 73 % (100 % through 2. Pd, H2, AcOH/MeOH CCl acidic decomposition) 3. CH2N2 N 4 N pyridine O 4. !, 21 % O N N rt RNH2 LiAlH4, THF, OH C O OH N tBuOCl N OH O NH 36 % N R N N O separable, but both dia- RNHNH2 MeOH O stereomers are not Retamine N + O N MeOH aq. H2SO4 OH HN 0 ºC, 2 d 29 % 21 % OH OAc CN OAc CO2Et R 29 % 1. aq. NaOH, H2CO 1. EtOH, HCl 2. Ac O, 74 % 2. Ac O, 3. KCN 2 C-H-activation: Müller: Chem. Ber. 1965, 98, 3493. N 2 N (over last N 10 g Cl 3 steps) 2 H O H + h" OH NOCl C NO C N C N H O 1. Raney-Nickel, H2, 3.1 g 1. Ac O + Cl – HCl N 2 OH C H 2. 200 ºC OH CO2Et kat. HCl + H OH vacuum (cycl.) N NOH 1.4 g N EtO C N 2 NOH NOH N 10 g NOH N 3. LiAlH4, 0.5 g 4. separation, 4 g 80 % NOH O 2. EtOH, HCl 60 % (2:1) 37 % (1:1) (±)-Retamin (IR) chromatography, 30 mg Baran Group Meeting Chemische Berichte 1970 Niklas Schöne Origin of Papers Synthesis of Aromatic Erythrina Alkaloids: – even fewer papers from outside germany O CO2Et CO2Et 1. H2O/MeOH – although some e. g. from Budapest (Hungary), Cluj (Romania), benzene, p-TsOH O O NaOH, 80 % Sofia (Bulgaria), Sheffield (England), Rehovot (Israel), Milan (Italy), Brussels (Belgium), Tsu (Japan) OH O 2. Xylenes, – H O HO 95 % 2 – again no contributions from the USA! :-( OH 67 % O Mondon: Chem. Ber. 1970, 103, 1512. MeO Main Topics O MeO H2N – still sugars, heterocycles, steroids, nucleosids 85 % H3PO4 H – still all kinds of aromatic compounds, especially heterocycles O O N 78 % N O O – a little bit more peptide synthesis: activation of carboxylic groups of O HCO2H amino acids, protecting groups, determinaton of racemization in H MeO DMF peptide synthesis O 76 % O – phenylenes, benzannulenes OM N MeO O e OMe Miscellaneous MeO for proof of identity they used: cis-15,16-Dimethoxy- IR, NMR, UV, mp, elemental – Bohlmann still isolates and synthesizes only natural products with the MeO erythrinane-1,8-dione analysis, mass spectra, same unsaturated side chains, isolated for example from bellis perennis L. (daisy), also Criegee and Stetter still do the same as well Clarification of results from Belleu and from Boekelheide by Mondon: – less interesting papers, less fun to get through – still no enantioselective or metal catalyzed reactions H H – one paper was only about a crystal structure to figure out the structure Cl O HN O + and relative configuration of a really boring molecule O H+ N N N O 100 ºC Important Names and their Chemistry – p. 339: Eicher: Reaction of Cyclopropenes with Diazoalkanes Why is the product not consistent with the one obtained by Mondons route? – p. 369: Dürr: Photochemistry with Small Rings Mondon repeated Belleus route and found the following: – p. 389: Simchen: A New Pyridine Synthesis H H – p. 426: Roth: Stereochemistry of Sigmatropic 1,5-H Shifts – p. 573: Viehe: Ynamine Addition to Imines: Ring Expansion of HN O O + Heterocycles by Two Carbon Atoms H N LiAlH4 N O – p.