SECTION 12. «POT-POURRI» in Organic Synthesis (2018)

Transcription

1 SECTIN 12 «PT-PURRI» in rganic Synthesis (2018) 1

2 Total Synthesis of Erythromycin A via a Spiroketal ERYTRMYCIN A DESLNGCAMPS et al. Can. J. Chem. 1985, 63,

3 Tetrahydropyran Derivative as Starting Material DESLNGCAMPS et al. Can. J. Chem. 1985, 63,

4 Spiroketal Controlling Introduction of Stereogenic Centers PART I 4

5 Spiroketal Controlling Introduction of Stereogenic Centers PART II 5

6 Spiroketal Controlling Introduction of Stereogenic Centers PART III 6

7 Cyclic Carbonate Useful to pen Spiroketal System DESLNGCAMPS et al. Can. J. Chem. 1985, 63,

8 Synthesis of Woodward Carbamate Key Intermediate DESLNGCAMPS et al. Can. J. Chem. 1985, 63,

9 9

10

11 11

12 12

13 13

14 14

15 15

16 Total Synthesis of (+)-Cassaine Utilizing an Anionic Polycyclization Strategy K. Ravindar, P.-Y. Caron, P. Deslongchamps rg. Lett. 2013, 15, J. rg. Chem In Press. 16

17 FIN 17

18 18

19 19

20 20

21 21

22 22

23 23

24 24

25 25

26 26

27 27

28 28

29 29

30 30

31 31

32 32

33 33

34 34

35 35

36 36

37 Representative Examples of Anionic Polycyclization E p-ts, C 6 6 E E Cs 2 C 3, CCl 3, rt reflux % for 2 steps E = C C 2 t-bu 2 Me C 2 t-bu 5 6 Cyclization A E E Cs 2 C 3, C 2 Cl 2, rt 1 + then Si 2, 70% E = C SPh 2 Me Cyclization B (a) Lavallée, J.-F.; Deslongchamps, P. Tetrahedron Lett. 1988, 29, (b) Spino, C.; Deslongchamps, P. Tetrahedron Lett. 1990, 31,

38 Synthetic Analysis of (+)-Cassaine (1) C 2 Me (+)-Carvone (5) N Bn Ph 4 S 3 Bn ( )-Cassaine (1) 2 C 2 Me 38

39 Synthesis of b-keto Ester 4 (+)-Carvone (5) ref Li-liquid N 3 TF, C 3 I, -33 o C 2. NaB 4, Et -40 o 6 C 7 65% (2 steps) Na, BnBr 95% TF, reflux Bn Bn 9 1. mcpba, C 2 Cl 2, quant 2. K 2 C 3, Me, rt, 90% 3. PDC, DMF, 90% s 4 (4% in 2 ) NM, acetone: 2 2. Silica gel-nai Bn 4 C 2 Cl 2, 90% (2 steps) 8 1. Na, K, (Me) 2 C TF, 90% 2. PhSeCl, pyridine C 2 Cl 2, then 2 2, C 2 Cl 2, 94% Bn 4 Me 39

40 Synthesis of Tricycle Ph Me S C 2 Me Bn 4 Cs 2 C 3, EtAc rt, 48 h, 62% Bn 2 NaEt, Et rt, 90% 12 NaB 4 TF:Me (1:1) 12 Bn 12 TBSCl Imodiazole C 2Cl 2 96% 0 o C-rt -78 o C 10 min, 90% Bn 11 TBS TBS Bn Pd/C (10 wt %) EtAc, 2 (15 PSi) rt, 24 h, 90%

41 Plausible Mechanism for the Synthesis of cis-cis decalin Systems Me PhS E PhS E E Me E Me F G Me Me E E Me E I E Me CMe Me Cs 2 C 3 CCl 3 Me (cat) E Me J 8 (E=CMe) 41

42 Synthesis of Ketone Intermediate 19 TBS TBS A MMCl DIPEA 82% C Pd/C (10 wt %) EtAc, 2 (20 PSi) B rt, 48 h, 95% Route-A X-Ray Route-B TBS 1. MMCl DIPEA, 85% 2. NaB 4, Me 0 o C, 90% TBS Li, liquid N 3 TF:tBu(9:1) MM o C, 90% MM 85% 16 Na, PMBBr TF, reflux TBS MM 19 PMB 1. TBAF, TF 85% 2. PDC, DMF 90% MM 18 PMB 42

43 Synthesis of Vinyl Triflate 24 MM MM 1. Na, K dimethylcarbonate PMB 2. NaB 4, Et MM PMB -10 o C % (2 steps) pyridine SCl 2, 95% PMB Me 1. DIBAL-, C 2 Cl 2-78 o C-rt, 86% 2. Dess-Martin periodinane C 2 Cl 2, 90% Mg (powder) Me, rt 96% MM PMB Me Me Tf MM KMDS, TF Comins Triflimide PMB -78 o C, 60% MM PMB 43

44 Synthesis of (+)-Cassaine (1) Tf 1. DDQ C 2 Cl 2 : 2 94% Tf MM 2.DMP oxidation PMB C 2 Cl 2, 90% MM Pd(PPh 3 ) 2 Cl 2, NMP 100 PSi of C, 100 o C N, 90% N N (+)-Cassaine (1) LiBF 4 C 3 CN o C, 75% ref.14 MM 26 44

45 STRATEGY IS A PLAN usually starts with small molecules containing minimum functional groups and stereochemistry A GD PLAN: - MAXIMUM bond formation within a chemical step - MINIMUM functional group transformation activation (in situ) protection deprotection A GD YIELD: - high chemo-, regio-, and stereoselectivity TER ELEMENTS: 1) convergence 2) chronology of appearance of desired functional groups 45

46 46