Lewis Base Activation of Lewis Acids: Development of a Lewis Base Catalyzed Selenolactonization

Transcription

1 Lewis Base Activation of Lewis Acids: Development of a Lewis Base Catalyzed Selenolactonization Denmark, S.E. and Collins, W.R. rg. Lett. 2007, 9, C 2 H + Se Lewis Base CH 2 Cl 2 Se Presented by: Melissa Sprachman ctober 27, 2007 Melissa Wipf Group 1 10/29/2007

2 Lactonization Reactions Halolactonization: Corey s Prostaglandin Synthesis J. Am. Chem. Soc. 1970, 92, 397. H H CH 3 KI 3 1. Ac 2, pyr, 2. Bu 3 SnH, H H 2, 20 h 97% I (99%, two steps) H CH 3 H CH 3 Mechanism-- Markovnikov Addn: (CH 2 ) 3 C 2 H - - H C 2 H C 2 + H C 2 - H 3 C CH 3 H H n-c 5 H 11 J. rg. Chem. 1975, 40, major Selenolactonization: icolaou s Prostaglandin Synthesis J. Am. Chem. Soc. 1981, 103, H CCH 3 SeCl, CH 2 Cl 2 CCH 3 Se H H H H Melissa Wipf Group 2 10/29/2007

3 Development of rganoselenium Chemistry Sharpless: Preparation of Allylic Alcohols: + SeX Se X RH Se R H 2 2 THF R J. rg. Chem. 1974, 39, 429. Campos, Clive: Cyclofunctionalization: H + SeCl Se J. Chem. Soc. Chem. Commun. 1977, 725. Clive, icolaou: Selenolactonization: C 2 H SeCl, Et 3 CH 2 Cl 2, -78 o C, quant. Se H 2 2, THF Raney i, THF J. Am. Chem. 1977, 99, Melissa Wipf Group 3 10/29/2007

4 Recent Developments in Selenium Chemistry Selenium catalyzed halolactonization: H + cat, SeSe CH 3 C R SeSe Se Se SeSe R R H H J. rg. Chem. 2004, 69, Melissa Wipf Group 4 10/29/2007

5 Developments in Selenium Chemistry Use of Enantiopure Selenium Reagents: Se + Tf - C 2 H SeAr * Tetrahedron Lett. 1997, 38, % de, 62% yield Catalytic Use of Selenium Electrophiles: R C 2 H 5 mol % SeSe I(CCF 3 ) 2 CH 3 C, rt (70%) R C 2 H rg. Lett. 2007, 9, Melissa Wipf Group 5 10/29/2007

6 Initial Studies on the Mechanism of Selenolactonization R 1 R 2 Proposed Mechanism of Selenocyclization: Se X R1 R 2 + SeX R 1 R 2 Se X - R 1 X R 2 Se --Based on initial observation of stereospecific anti-addition of benzenesleneyl halides to alkenes --Both the episelenurane and the seleniranium ion have been isolated and characterized Denmark et al. J. rg. Chem. 2006, 71, 7293 Melissa Wipf Group 6 10/29/2007

7 Lewis Base Activation of Lewis Acids P(Me 2 ) 3 SiCl + Cl 4 P Cl Si Me 2 Me 2 Me2 Cl P(Me 2 ) 3 Cl SnBu 3 + CH Me P Me Me SiCl 4 (1.1 equiv), CH 2 Cl 2, -78 o C CH 2 2 (5 mol %) H Via LB LB Cl Si Cl Cl H Cl Denmark, S. E. in Modern Aldol Reactions; Marhwalk, R., Ed.: Wiley- VCH: Weinheim, 2004 Activation of a Selenium Electrophile? Se X L L D L δ + L δ - δ + δ - L D Se X L L L L D Se X + X - Melissa Wipf Group 7 10/29/2007

8 Development of a Lewis Base Promoted Selenolactonization Initially studied reaction: C 2 H SeCl CH 2 Cl 2 Se C 2 H R 2 -Se CH 2 Cl 2, 23 o C, 3h Se --Benzeneselenyl chloride reacts with olefins spontaneously at cryogenic temperatures --Competitive pathways of seleniranium ion trapping and reversible formation of seleniranium ion exist ---> Choice of Leaving Group is Critical Selenamide Yield of Selenolactone (%) Se 87 Se 79 Se 18 Se 8 Melissa Wipf Group 8 10/29/2007

9 Finding a Feasible Lewis Base Activator **Use of softer chalcogens enhanced reaction efficiency: Reaction times ranged from 3 h with HMPA to 10 min with thiophosphoramide to < 5 min with selenophosphoramide! Melissa Wipf Group 9 10/29/2007

10 Survey of Lewis Bases --> Isolated ~10% Selenol ester Se Melissa Wipf Group 10 10/29/2007

11 Mechanistic Insight: bservation of an HMPT-Selenium Adduct Se + CD 2 Cl 2 P 23 o C, 30s Me 2 Me 2 Me2 Me 2 Me 2 P Me 2 Se Prior to lefin Coordination Either 1.) Ionization of the -Se bond to form a contact ion pair or 2) Activation of the succinimide LG to form a selenium cation Role of the Carboxylate Proton: Melissa Wipf Group 11 10/29/2007

12 Postulated Catalytic Cycle Based on Collective Data Melissa Wipf Group 12 10/29/2007

13 Recent Developments in Electrophile-Promoted Cyclizations t-bu Co t-bu 1. I 2, CH 2 Cl 2-78 o C 2. H I t-bu t-bu J. Am. Chem. Soc. 2003, 125, u* = Si 3 P H Si 3 ature, 2007, 445, 900. Melissa Wipf Group 13 10/29/2007

14 Summary and utlook -- Lewis base catalyzed selenolactonization was performed, and viable proof for reaction intermediates was established. --The successful suppression of the background reaction and rapid turnover rate make asymmetric modifications a possibility. -- The inherent toxicity of selenium may prove a barrier in the overall utility of these transformations; however, the concept of Lewis base activation of electrophiles is worthwhile. Melissa Wipf Group 14 10/29/2007

15 Development of a Lewis Base Promoted Selenolactonization C 2 H SeCl CH 2 Cl 2 Se --Benzeneselenyl chloride reacts with olefins spontaneously at cryogenic temperatures --Competitive pathways of seleniranium ion trapping and reversible formation of seleniranium ion exist ---> Choice of Leaving Group is Critical Melissa Wipf Group 15 10/29/2007