JOC YEAR IN REVIEW 1972

Transcription

1 JC YEAR IN REVIEW 1972 ALEXANDRS ZGRAFS TE BARAN GRUP MEETING 08/20/2003

2 The difficult decision Some statistics!number of articles 1225!!Full articles 480!More than 25 total synthesis!isolation and characterization of 52 molecules!several novel methods

3 Total synthesis C C (-)-Seychellene Mirestrol Prostagladins C Cubane derivatives Guaiol N Dehydrojoubertiamine Cinobufacin (-)-Patchouli alcohol Jasmone

4 Total Synthesis of cis-jasmone! Isolated from flower oils of Jasminum! Indispensable in the reproduction of jasmine fragrance! Several preparations have been reported First synthesis at 1952 by arper! Two total synthesis in Crombie, L.; arper, S.; J. Chem Soc.; 1952, 869; arper, S; Smith, J.; J. Chem. Soc.; 1955, 1512; Buchi, G.; Egger, B.; J. rg. Chem.; 1971, 36, 2021; Mc Murry, J.; Melton, J.; J. Am. Chem. Soc.; 1971, 93, 5309.

5 Two Efficient Methods for the Construction of cis-jasmone Berkowitz, W.; J. rg. Chem., 1972, 37, 341; Grieco, P.; J. rg. Chem., 1972, 37, Cl Cl C Corey, E.; Tetr. Lett., 1970, Cl Cl Et 3 N, 0 0 C hexanes Cl Cl Zn, Acetic acid 2 2 Acetic acid DIBAL Toluene C Cl Ph 3 P=CC 2 C 3 DMS 1.MeLi 2.Cr 3 Na/ C Jones Reagent Jasmone Berkowitz, W.;J. rg. Chem. 1971, 36, C glass wool -Et, C Cl Na Benzene cyclopropyloxopropanoate

6 ighlights Baeyer-Villiger Ring Expansion 2 2 acetic acid A Thermal Two Carbon Ring-Expansion + C C -Et Glass catalysed Si Si + C Et

7 Total Synthesis of Patchouli Alcohol!A tricyclic sesquiterpene isolated from patchouli oil!an important raw material for the composition of perfumes!first total synthesis by Buchi at 1956 Buchi, G.; Erickson, R.; J. Am. Chem. Soc., 1956, 78, 1262; Buchi, G.; Erickson, R.; J. Am. Chem. Soc., 1961, 927; Buchi, G.; McLeod, W.; J. Am. Chem. Soc., 1962, 84, 3205; Buchi, G.; McLeod, W.; Padilla,.; J. Am. Chem. Soc., 1964, 86, 4438.

8 A Synthetic Route to Racemic Patchouli Alcohol Mirrington, R.; Schmalzl, K.; J. rg. Chem., 1972, 37, Diels Alder Zn 1.B 2 6, TF 2.Cr 3 pyridine Tr TrCl Et 3 N + Li,N 3 Et + PCl pyridine AcCl DMA Na, MeI Tr Ratio 4:1 Both E and Z regioisomers EtNa Tr 3 steps I Na sealed tube C Mirrington, R.;Tetr.Lett., 1969, Danishefsky, D.; Chem.Commun., 1968, (-)-Patchouli alcohol

9 ighlights + maybe by carbocation AcCl :B Base elimination Both E and Z regioisomers Assisted cleavage Li, N 3 Et Selective dehydration 4 1 Proton attacks from the less hindered side Stereochemistry of the reduction

10 Synthesis f Cubane Derivatives C! Interesting molecular structure! riginal work by Eaton et al. at 1964 reporting several derivatives of cubane skeleton! First synthesis of homocubane from 2- cyclopentanone in less than 10% yield

11 A Facile Synthesis of omocubane Paquette, L.; Ward, J.; J. rg. Chem., 1972, 37, 3569 Se 2 Jones Reagent Et 3 N First synthesis of cubane derivatives hv C C 1.K 2. 3 hv C 1.K NBS, CCl , pent-dcm Et 2 N, C Spontaneous dimerization Favorskii type rearrangement Eaton, P.; Cole, T.; J. Am. Chem. Soc., 1964, 86, 962

12 ighlights Spontaneous cyclization of bromo-cyclopentanones Anintermolecular Diels-Alder Reaction Favorable intermediate Favorskii type rearrangement - C

13 Total Synthesis of Prostaglandins F 1a and E 1 Prostaglandin F 1a Prostaglandin E 1! Prostaglandins are discovered by von Euler in 1932! Carbocyclic oxygenated C-20 molecules are hormones that elicit an unusually diverse array of physiological response! Several preparations have been reported

14 A New Method for the Preparation of Prostaglandins Schaaf, T.; Corey, E.; J. rg. Chem., 1972, 37, 2921 TP C 2 Ph 1.TP, Ts 2.DIBAL C TP P(Me) 2 Na, DME TP C 2 Ph Ph 3 P Corey, E.; J. Am. Chem. Soc., 1968, 90, 3247 DMS, Na TP Corey, E.; J. Am. Chem. Soc., 1969, 91, 5675 Collins Reagent, DCM 0 0 C TP C 2 Ph 1.C 2 N 2, ether 2.Ac 2, pyridine 50 0 C 3. 2, Pd/C 1atm 5%Acetic acid Ethanol NaB 4 DME, 25 0 C 1.Acetic acid/ 2, 40 0 C 2.separation of epimers 3.K, Me, TF, 25 0 C TP Prostaglandin F 1a Prostaglandin E 1

15 ighlights Synthesis of Corey s lactone Na, TF BnC 2 Cl C Ph 2 C Ph 2 C Cl CN Cu(BF 4 ) 2, 0 0 C Cl CN K, 2 DMS Ph 2 C mcpba NaC 3 DCM 1.Ac 2, pyr. 2.n-Bu 3 Sn AIBN, Ph I KI 3, NaC 3 2, 0 0 C Na, 2 Ph 2 C Ac C 2 Ph C 2 Ph C 2 Ph C 2

16 Novel Methods! Thallium chemistry in organic synthesis! Novel etherification of alcohols! Palladium-Catalyzed Vinylic ydrogen Substitution (eck reaction)

17 Novel Etherification of Alcohols Kashman Y.; J. rg. Chem., 1972, 37, 912 Dialkyl phosphites react with alcohols to give the corresponding ether in the presence of catalytic amount of acid R P(C 3 ) 2 P R: C 8 17 P(C 3 ) 2 + R: P R protonated dimethyl phospite P RC 3

18 Paladium-catalyzed Vinylic ydrogen Substitution Background before the discovery of eck Reaction RMX + M' R M'X R + M'X M: g, Sn, etc example: gac + Pd(Ac) 2 + g(ac) 2 Transmetaletion Easy to isolate PdAc PdAc + PdAc + PdAc PdAc PdAc β-elimination + + +

19 Disadvantages! There is often a problem obtaining the organomercury, lead or tin compounds! Thick slurries of salts difficult to manipulate if the reaction is carried out catalytically in palladium

20 A New Method for the Arylation and Benzylation of Vinylic ydrogen eck R.; Nolley, J.; J. rg. Chem., 1972, 37, 2320 Mechanism of eck Reaction RX + Pd RPdX RPdX + R PdX Use of a base is essential in order to neutralize the hydrogen halide from the reaction Tolerate a number of functional groups Iodides react rapidly. Benzyl halides are less reactive Loss of stereochemistry. Both cis and trans products R PdX

21 Thalium Chemistry in rganic Synthesis Background! Thalium acetate was first described at 1903 by Meyer and Goldschmidt! Among its applications are oxidative cleavage of cyclopropanes, the conversion of chalcones into isoflavones and the hydration of acetylenes Year 1972! Direct synthesis of allenic esters from β- ketoesters! xidation of cyclohexanones to adipoins

22 A New Synthesis of Allenic Esters Taylor, E.; Robey, R.; McKillop, A.; J. rg. Chem., 1972, 37, 2797 R 1 R 2 R 3 R 2 N-N 2 R 1 R R 3 2 N N TTN Me R 1 R 3 R 2 C C C R 1, R 2, R 3 =alkyl Mechanism R 1 R 2 R 3 R 1 R 2 R 3 TTN R 1 R R 3 2 Tl(N 3 ) 2 N N N N N N - 2 R 1 R 3 R 2 C C C R 1 R R 3 2 Tl(N 3 ) 2 N N TTN R 1 R R 3 2 Tl(N 3 ) 2 N N Me

23 xidation of Cyclohexane to Adipoins McKillop, A.; und, J.; J. rg. Chem., 1972, 37, 3381 McKillop, A. et al. J. Am. Chem. Soc., 1971, 93, 4919 Tl Y Y C +