Baran Group Meeting Derek H. R. Barton Will Gutekunst Quick Timeline - Born Derek Harold Richard Barton on Sept. 18, 1918 - Father died in 1935 and had to take over the family wood business. - In 1937 decided to leave family business and enrolled at London University. - Entered Imperial College in 1938 after passing entrance exams and graduated two years later. Graduate work focused on the synthesis of vinyl chloride - Completed his Ph.D. 1942 and started working with military intelligence developing nonaqueous secret inks. - At the end of the war he started work with Albright and Wilson, Ltd. on the synthesis of organophosphorus compounds. - In 1946 he took the "most junior position" at Imperial College as an assistant lecturer. - From 1949-1950 he was a visiting lecturer at Harvard - In 1950 he was appointed reader at Birkbeck College, then to professor in 1953. - 1955 he moved to University of Glasgow - In 1957 he moved (yet again) to Imperial College - Received the Nobel Prize with Odd Hassel in 1969 for his development of Conformational Analysis - Knighted in 1972 (but only known as "Sir" in Britain) - Moved to France in 1978 to become director of ICSN - Gif Sur-Yvette - Forced to retire, moved to Texas A&M in 1986 - Died 1998 at the age of 79 Flour Beetle Study Main Areas of Research: 6 days Flour + dead beetle pink (and unpalatable) flour surrounding beetle - Conformational Analysis - Stucture Elucidation - Phenol Oxidation Compound isolation: - Biosynthesis (lignans, phenolic 500-1000 adult beetles (ca. 5 mL) are placed in a distilling flask. A stream of dry air alkaloids, steroids, triterpenes) is passed through the flask for 6 hours. Every 2 hours, cool to 0° C for 20 minutes. - Radical Chemistry The excretion condensed long yellow needles on the cold finger (0.5 mg). Return beetles to flour for 3 days and repeat. Yields reduce with each interation. After 3 or - Photochemistry - Fluorine Chemistry 4 operations the insects were too feeble for further excretion. - Organometallics - Much, much more O Biochem. J. 1943, 37, 463-465 In all of these fields Barton made important contributions, if now start the field altogether. He frequently changed fields stating" O "... I have worked in many fields, but as ethylquinone! soon as these fields became popular, I have moved on. I have made the joke After a battey of tests, Barton determined that the compound was ethylquinone and of saying that if you cannot remember when the paper was submitted the journal's editor initially thought it was a joke. This all the published papers in the field you early study was performed during his free time when he was working for military are working in, then it is time to move intelligence, stating, "I though then, as now, that chemistry is more interesting that on." Gap Jumping, page 111. spare time." Gap Jumping, page 9. Baran Group Meeting Derek H. R. Barton Will Gutekunst Method of Molecular Rotation Differences Vinyl chlorides Me Me Studied the thermal decomposition of various polychlorinated hydrocarbons and found that can J. Chem. Soc. 1945, 813-819 occur through three different pathways. Me Cl ~300–500° C H Cl H cis-elimination + H Cl H Cl Me H H H RO Cl Cl + H Cl cholesterol radical chain Cl H Cl Cl Cl Cl + Cl Cl R R R H H H H R Cl "surface" Me H Me H Me Me H Cl surface catalyzed + H Cl H Cl H H H H H H RO RO RO RO H H H J. Chem. Soc. 1949, 155. R H H R H R Notably, 1,1 dichloroethane cannot participate in radical chain processes Me Me Me H Cl Cl Cl Cl Me + Cl H H H H HCl Me H RO RO RO H H H Established "rules" for the decomposition of any chlorinated hydrocarbon. Cl Later extended to polyunsaturated compounds, hormones and bile acids ! Cl Me Cl + H Cl J. Chem. Soc. 1946, 512 Cl Cl J. Chem. Soc. 1946, 1116 At a given temperature and surface area/volume ratio, all three mechanisms operate at the same rate. This method, while empirical, was accurate. Barton used to correct numerous structures in the literature - even one assigned by Nobel laureate Leopold Ruzicka! "It was perhaps unwise for a young J. Am. Chem. Soc. 1950, 72, 988. man to criticize a distinguished professor at the prestigious ETH... I showed that L. Ruzicka had made an error in the assignment of configuration at the C-3 position in ring A of triterpenoid alcohols. Ruzicka, one of the greatest organic chemists of the day, had received the Nobel Prize just before the war. He was a passionate and fiery man. Our relations for some years were confied to print and somewhat strained" Baran Group Meeting Derek H. R. Barton Will Gutekunst cis-Elimination Me Me Δ H AcO OBz AcO H H Originally reported by Plattner (ETH), refuted by MMRD Me Me Δ H H AcO OBz AcO H H Inspired by previous work, realizes it is requisite cis-elimination! J. Chem. Soc. 1949, 2174. J. Chem. Soc. 1949, 2459. Me Me Me Δ + Using this analysis, he was able to rationalize the relative rates of esterification of Cl unimolecular equatorial and axial (polar) alcohols, thermodynamic isomerizations, anti-periplanar geometries for elimination, neighboring group participation, etc. Me Me Me Me Me Me "Conformational Analysis for the sutdy of the stability and reactivity of saturate or partly saturated cyclic systems promises to have the same degree of importance as Further support with menthyl chloride pyrolysis J. Chem. Soc. 1953, 453. the use of resonance in aromatic systems." – Arthur J. Birch, 1951 Conformational Analysis "Conformational Transmission" Insprired by Odd Hassl's paper on decalin conformation, Barton became interested in calculating Remote conformational effects drastically change the relative rates of aldol reaction. the preferred conformations using force field calculations (logarithmic tables and slide rule!) Nature 1946, 157, 765. J. Chem. Soc. 1948, 340. Me H Me Me H H H H H H H H H H H or ? or H H ? O O O H H H H 4 H H H H 1 645 preferred! J. Chem. Soc. 1960, 1297. This eventually led to the application of these concepts to steroid conformation Experientia 1950, 6, 316. Baran Group Meeting Derek H. R. Barton Will Gutekunst Structure Elucidation O Me O Me O Me O Me Me O Me Me H Me O Me O O O O Me O O Me Me Me Me H glauconic acid byssochlamic acid H Me caryophyllene J. Chem. Soc. 1965, 1769. H Me Me J. Chem. Soc. 1951, 2988. J. Chem. Soc. 1952, 2210. !-amyrin J. Chem. Soc. 1953, 1027. OMe Cl Me O Me Me O Me Me Me Cl Me Me Me RO2C O OH H H OH OH Me Me Me H R = Me; geodin Me Me culmorin R = H; erdin Me Me J. Chem. Soc. (C) 1968, 1148. J. Chem. Soc. 1958, 1767. HO HO H H Me Me Me Me cycloartenol lanosterol O J. Chem. Soc. 1951, 1444. H O J. Chem. Soc. 1953, 576. O H O H Me H Me O Me O Me Me Me H O Me HO O O H O Me Me O OAc H AcO Me H OH H AcO O Me N Me HO Me clerodin limonin O OAc OH HO Me H J. Chem. Soc. 1961, 5061. J. Chem. Soc. 1961, 255. HO OH Me Me OH Me H Me OH Me O H OH Me HO Me H HO Me Me H VO5, HNO3 OH MeO H meso compound onocerin cevine "good yield" fusicoccin H J. Chem. Soc. 1955, 2639. J. Chem. Soc. 1954,3950. ` HO2C Me J. Chem. Soc. 1971, 1259; 1265. abietic acid Baran Group Meeting Derek H. R. Barton Will Gutekunst Structure Elucidation O Me O Me O Me O Me Me O Me Me H Me O Me O O O O Me O O Me Me Me Me H glauconic acid byssochlamic acid H Me caryophyllene J. Chem. Soc. 1965, 1769. H Me Me J. Chem. Soc. 1951, 2988. J. Chem. Soc. 1952, 2210. !-amyrin J. Chem. Soc. 1953, 1027. OMe Cl Me O Me Me O Me Me Me Cl Me Me Me RO2C O OH H H OH OH Me Me Me H R = Me; geodin Me Me culmorin R = H; erdin Me Me J. Chem. Soc. (C) 1968, 1148. J. Chem. Soc. 1958, 1767. HO HO H H Me Me Me Me cycloartenol lanosterol O J. Chem. Soc. 1951, 1444. H O J. Chem. Soc. 1953, 576. O H O H Me H Me O Me O Me Me Me H O Me HO O O H O Me Me O OAc H AcO Me H OH H AcO O Me N Me HO Me clerodin limonin O OAc OH HO Me H J. Chem. Soc. 1961, 5061. J. Chem. Soc. 1961, 255. HO OH Me Me OH Me H Me OH Me O H OH Me HO Me CO H H HO 2 Me Me H VO5, HNO3 Me OH MeO H onocerin cevine "good yield" fusicoccin CO2H ` HO C H J. Chem. Soc. 1955, 2639. J. Chem. Soc. 1954,3950. 2 Me HO2C Me J. Chem. Soc. 1971, 1259; 1265. abietic acid Baran Group Meeting Derek H. R. Barton Will Gutekunst Oxidative Phenol Couping and Biosynthetic Implications These studies were initiated by a disbelief of the proposed structure of "Pummerer's ketone," despite being commonly held as true for 25 years. OH O OH J. Chem. Soc. 1956, 530. K3[Fe(CN)6] Me Me NMe high dilution LAH NMe H O NMe O K [Fe(CN) ] O OH 3 6 HO O 1.4% Me O O MeO MeO MeO Me Me narwedine galanthamine "Pummer's ketone" J.