D.A. Evans Ambiphilic Functional Groups-2: Sulfur-Based Activating Groups Chem 206 http://www.courses.fasharvardedu/-chem206/ Relevant Background Reading N.s. Sulphones in Organic Synthesis Pergamon Press, New York, 1993 Chemistry 206 General: Magnus, P D. Tetrahedron 1977, 33, 2019 Advanced Organic chemist Julia: Kocienski, P.J. Chem. Ind. London)1981, 548 Electrophilic Properties: Trost, B M. Bull. Chem. Soc. Jpn. 1988, 61, 107. Lecture number 27 So2 Extrusion: Vogtle, F. Rossa, L. ACIEE 1979, 18, 515 Ambiphilic Functional Groups-2 Ramberg-Backlund Rxn: Paquette, L.A. Org. Reactions 1977, 25, 1 Sulfur-Based Activating Groups Triflones: Hendrickson, J B. Org. Prep. Proc. Int. 1977, 175 ■ Sulfur - Ylides Sulfoximides: Johnson C.R. Tetrahedron 1984. 40. 122 Sulfur -Stabilized carbanions: Structure ve construction of trans olefins through carbanion-mediated tion processes has still not been rendered general. One Sulfone-Based Transformations transformation that sed in certain circumstances is the one-step"Julia transformation illustr Provide a mechanism for this transformation Pummerer rearrangement so Rs ARA RACHO Reading Assignment for this Week: H78t025℃ Carey& Sundberg: Part A; Chapter 7 carbanions& Other Nucleophilic Carbon Species Carey Sundberg: Part B: Chapter 2 The cruel mechanistic problems that you should be prepared for in Chem 206 Reactions of Carbon Nucleophiles with Carbonyl Compounds Chemical Chameleons: Organosulfones as Synthetic Building Blocks AC2O/HOAC B M. Trost, Bull. chem. Soc. Japan, 1988, 61, 107-124(handout Meo Meo Matthew d shair Meo November 20. 2002 Padwa et al. Joc 1996. 61. 48
http://www.courses.fas.harvard.edu/~chem206/ N S S O O H RS RACHO MeO MeO N O O S O Et CO2Me RS RA RS RA N CO2Me O O MeO MeO N H S O D. A. Evans Chem 206 Matthew D. Shair Wednesday, November 20, 2002 Reading Assignment for this Week: Ambiphilic Functional Groups–2: Sulfur-Based Activating Groups Chemistry 206 Advanced Organic Chemistry Lecture Number 27 Ambiphilic Functional Groups–2 Sulfur-Based Activating Groups ■ Sulfur-Ylides ■ Sulfur-Stabilized Carbanions: Structure ■ Sulfone-Based Transformations ■ Pummerer Rearrangement Relevant Background Reading General: General: Julia: Electrophilic Properties: SO2 Extrusion: Ramberg-Bäcklund Rxn: Triflones: Sulfoximides: Simpkins, N.S. Sulphones in Organic Synthesis, Pergamon Press, New York, 1993. Magnus, P.D. Tetrahedron 1977, 33, 2019. Kocienski, P.J. Chem. Ind.(London) 1981, 548. Trost, B.M. Bull.Chem. Soc. Jpn. 1988, 61, 107. Vogtle, F.; Rossa, L. ACIEE 1979, 18, 515. Paquette, L.A. Org. Reactions 1977, 25, 1. Hendrickson, J.B. Org. Prep. Proc. Int. 1977, 175. Johnson, C.R. Tetrahedron 1984, 40, 1225 Cume Question, 1998: The stereoselective construction of trans olefins through carbanion-mediated condensation processes has still not been rendered general. One transformation that may be used in certain circumstances is the "one-step" Julia transformation illustrated below. Provide a mechanism for this transformation. 1 LiN(iPr)2 THF -78 to 25 °C + + + SO2 "Chemical Chameleons: Organosulfones as Synthetic Building Blocks" B. M. Trost, Bull. chem. Soc. Japan, 1988, 61, 107-124 (handout) Ac2O/HOAc 70% The cruel mechanistic problems that you should be prepared for in Chem 206 Padwa et al. JOC 1996, 61, 4888 Carey & Sundberg: Part A; Chapter 7 Carbanions & Other Nucleophilic Carbon Species Carey & Sundberg: Part B; Chapter 2 Reactions of Carbon Nucleophiles with Carbonyl Compounds
D.A. Evans Sulfur-Based Functional Groups-1 Chem 206 Relevant Background Reading Reactions of sulfonium ylids m, Prs, New rer k 193. ic Synthesis General: Magnus, P D. Tetrahedron 1977, 33, 2019. Sulfonium Salt: pKa- 18 Julia: Kocienskl, P.J. Chem Ind. London)1981, 548. Electrophilic Properties: Trost, B M. Bul. Chem. Soc. Jpn. 1988, 61, 107. SO2 Extrusion: Vogtle, F Rossa, L. ACIEE 1979, 18, 515 Ramberg- Backlund Rxn: Paquette, LA Org. Reactions 1977, 25, 1 o-P=0 Triflones: Hendrickson, J B. Org. Prep. Proc. Int. 1977, 175. OH OH Sulfoximides: Johnson. C.R. Tetrahedron 1984. 40. 1225 S-Adenosylmethionine Acidities of Sulfur-based Functional Groups a Deprotonation: S-CH2+ Na-H H-H pKa (DMso H4 pKa-18 pKa (-56 H3 Leaving Group Potential: R2S--C(+ Sulfoxide 35pKa(-41) L L-S-CH3 Nu +Me-№u pKa 31 Excellent LG Sulfonium salt Bordwell, F. G. Zhang X.-M. Acc Chem. Res. 1993, 26, 510-17 Good lG
S CH3 CH3 CH3 S CH3 R R S R R S CH3 R R O N N N N NH2 OH OH S HO Me NH2 O S CH2 R R S CH3 R R S R R + + + + + + Me I CH3 S CH3 CH3 S CH3 O S O CH3 CH3 O Na H O NH2 S Me HO OH OH NH2 N N N N O O P R O – O O S O R CH3 O S CH3 L L L R2S C(+) CH4 NH3 HOH SN2 S O O – R L S: L L Me Nu Me Nu H H Me Nu D. A. Evans Chem 206 Relevant Background Reading pKa (~56) pKa 31 pKa (~41) Sulfide Sulfoxide Sulfone Sulfonium Salt pKa (DMSO) ~ 18 ~ 31 (45) ~35 Sulfonium Salt: pKa ~ 18 Reactions of Sulfonium Ylids ■ Synthesis: ●● SN2 + I – S-Adenosylmethionine SN2 + ●● ■ Deprotonation: – pKa ~ 38 pKa ~ 18 Sulfur-Based Functional Groups-1 Bordwell, F. G.; Zhang, X.-M. Acc. Chem. Res. 1993, 26, 510-17. Good LG Excellent LG ●● ●● SN2 + Nu: + + Nu: + SN2 + (+) + Nu: ■ Leaving Group Potential: Acidities of Sulfur-based Functional Groups General: General: Julia: Electrophilic Properties: SO2 Extrusion: Ramberg-Bäcklund Rxn: Triflones: Sulfoximides: Simpkins, N.S. Sulphones in Organic Synthesis, Pergamon Press, New York, 1993. Magnus, P.D. Tetrahedron 1977, 33, 2019. Kocienski, P.J. Chem. Ind.(London) 1981, 548. Trost, B.M. Bull.Chem. Soc. Jpn. 1988, 61, 107. Vogtle, F.; Rossa, L. ACIEE 1979, 18, 515. Paquette, L.A. Org. Reactions 1977, 25, 1. Hendrickson, J.B. Org. Prep. Proc. Int. 1977, 175. Johnson, C.R. Tetrahedron 1984, 40, 1225
D. A. Evans. K. Scheidt X-ray Structures of Metallated Sulfones Sulfoxides Chem 206 Sulfone& Sulfoxide based carbanions. Structure o Me Boche, etal. Angew. Chem. Int Ed 1986, 25, 1101 Sulfone-and sulfoxide-stabilized carbanions are extremely useful carbon nucleophiles in organic synthesis TMEDA A-s—cH E+) Ar-S—cH E(+) However, until recently little information was available on the solid state The Structure of Lithium Coumpounds of Sulfones, Sulfoximides, Sulfoxides, Thioethers, 1, 3 Dithianes, Nitriles, Nitro Compounds, and Hydrazones Boche, G. Angew. Chem., Int. Ed Engl. 1989, 28, 277 Here are several examples taken from the Boche review. CH2-LHTMEDA w. Chem. Int Ed. 1 The Li counterions are not associated with the charged carbon The carbanions are largely trigonal
Ar S O CH3 Ar S O O CH3 S O O CH2–Li–[TMEDA] Ar S O CH2–Li Ar S O O CH2–Li Li Li Ar S O CH2 El Ar S O O CH2 El S O C–Li Me Li Li Li Chem 206 Sulfone- & Sulfoxide Based Carbanions: Structure X-ray Structures of Metallated Sulfones & Sulfoxides LDA El(+) ■ Sulfone- and sulfoxide-stabilized carbanions are extremely useful carbon nucleophiles in organic synthesis. However, until recently little information was available on the solid state structures of these species: LDA El(+) "The Structure of Lithium Coumpounds of Sulfones, Sulfoximides, Sulfoxides, Thioethers, 1,3 Dithianes, Nitriles, Nitro Compounds, and Hydrazones." Boche, G. Angew. Chem., Int. Ed. Engl. 1989, 28, 277. Here are several examples taken from the Boche review: Gais, etal. Angew. Chem. Int. Ed. 1985, 24, 859 Boche, etal. Angew. Chem. Int. Ed. 1986, 25, 1101 + TMEDA ■ The Li counterions are not associated with the charged carbon. ■ The carbanions are largely trigonal. D. A. Evans, K. Scheidt
D. A Evans. K scheidt X-ray Structures of Phenylsulfinyl Carbanions Chem 206 TMEDA TMEDA Boche, etal. Angew. Chem. Int. Ed. 1986, 25, 1101 Boche, etal. Angew. Chem. Int. Ed. 1985, 24, 573
S O C–Li Me Li Li Li S O O CH–Li Li Li D. A. Evans, K. Scheidt X-ray Structures of Phenylsulfinyl Carbanions Chem 206 Boche, etal. Angew. Chem. Int. Ed. 1986, 25, 1101 Boche, etal. Angew. Chem. Int. Ed. 1985, 24, 573 + TMEDA + TMEDA
D A. Evans Sulfur-Based Functional Groups-2 Chem 206 Reactions with ketones (王) Reactions of sulfones R2s--C Reactivity Pattern: Nonaltemate Synthesis: 0 H2O2 R2S R2S Good review article: Magnus, Tetrahedron 1977, 33, 2019-2045. Twenty-five Years of Dimethylsulfoxonium Methylide(Corey's Reagent) Gololobov, Y. G. Lysenko, V P ; Boldeskul, L. E. Tetrahedron 1987, 43, 2609 Reactions of sulfone Reactions of Sulfonium Ylids: Conjugate Addition more nucleophilic (-) R2SO2--C S-CH3 R2s- Cn pogue tang R2SO2-C Nonaltemate reactivity pattem revealed in (+) consecutive reactions R2S--C ? 1, 2-vS 1.4-addition ? Will function as lG ?
CH2 O – S Me Me S Me Me CH2 O – C H H S Me Me C H H S Me Me S Me Me O – S Me Me S Me Me O – S CH2 Me Me S CH2 R R S CH3 R R + + + + – + + + + + O O R2S C CH2 O R2S C Me Br Me Me Me Br :S Ph O O – H2O2 S Ph Me Me O O Me Me S Ph O CH2 R2S C O O R2S C R2S C Li O S Ph Me Me O O S O O Me Me Ph Li S O O Me Me Ph S Ph Me Me O O R2SO2 C BuLi H2O2 HIO4 R2SO2 C S Ph Me Me O O S Me Me O Ph D. A. Evans Sulfur-Based Functional Groups-2 Chem 206 – (+) (–) Reactivity Pattern: Nonalternate ■ Reactions with ketones: (±) "Twenty-five Years of Dimethylsulfoxonium Methylide (Corey's Reagent).", Gololobov, Y. G.; Lysenko, V. P.; Boldeskul, I. E. Tetrahedron 1987, 43, 2609. Nonalternate reactivity pattern revealed in consecutive reactions (+) (+) (–) Reactions of Sulfonium Ylids: Conjugate Addition ●● – Sulfinate ester not observed (Sulfinate anion) PhS: – Synthesis: Reactions of Sulfones Good review article: Magnus, Tetrahedron 1977, 33, 2019-2045. Will function as LG ?? 1,2- vs 1,4-addition ?? ?? (+) poorer leaving group than: ●● – more nucleophilic than: pKa ~ 25 Reactions of Sulfones (+) (+) (–) +