Chemistry 206 Advanced Organic Chemistry Handout 27A Vicinal elimination reactions: An overview Introduction Overview of e2 Process Dehydration: Burgess Reagent Martin Sulfurane Selenoxide elimination applications Ramberg-Backland related cheletropic rxns Vicinal debromination and related rxns ■ The takai reaction ■ The McMurry reaction ■ The Julia reacti Matthew d, shair Wednesday November 20. 2002
■ Introduction & Overview of E2 Process ■ Dehydration: Burgess Reagent & Martin Sulfurane ■ Selenoxide Elimination & Applications ■ Ramberg-Backland & Related Cheletropic Rxns ■ Vicinal Debromination and Related Rxns ■ The Takai Reaction ■ The McMurry Reaction ■ The Julia Reaction Chemistry 206 Advanced Organic Chemistry Handout 27A Vicinal Elimination Reactions: An Overview Matthew D. Shair Wednesday, November, 20, 2002
D. A. Evans Elimination fragmentation Reactions in C=C Bond Constructions Chem 11 cussion is intended to provide a general overview L Elimination Reactions: The limiting of useful elimination reactions of value in the construction of olefins Trost, Ed, Comprehensive Organic Synthesis 1992, Vol 6, Chapter 5.1 Vicina/ Elimination reactions: One Heteroatom X-) Review. Lowry& Richardson, Mechanism Theory in Org. Chem., 3rd Ed, p 588-620 E1cb family base Organic Synthesis R1 Hoffmann Elimination base Stereochemistry;■The I The E2 process encompasses a range of synchronous geometries ■ Cope Elimination: △Δ Synthesis 53.p1011 X8- El-like ts E1cb-like Ts ■ Sulfoxide elimination A△△ a Why is the anti elimination geometry preferred anic Synthesis 6ch53,p1011 Forπ Bonds Better A Selenoxide Elimination: RI\ -HOSeA Stereochemistry G'C-x Better GC-H 00 than HOM 0 LUMO △△Δ a Acetate/Xanthate Pyrolysis 27A-01-Elimination Rxns 12/7/93 12: 00 PM Anti Geometry
D. A. Evans Elimination & Fragmentation Reactions in C=C Bond Constructions Chem 115 ■ Dehydrohalogenation: base ■ Selenoxide Elimination: Anti Stereochemistry Syn Stereochemistry ∆ –HOSeAr –HX –HONR2 ∆ Syn Stereochemistry ■ Cope Elimination: + – – + Anti Stereochemistry ■ Hoffmann Elimination: + – base –HNR3 Vicinal Elimination reactions: One Heteroatom – + –HOSAr ∆ Syn Stereochemistry ■ Sulfoxide Elimination: ∆ –HOXCR Syn Stereochemistry ■ Acetate/Xanthate Pyrolysis: H(+) X(–) The following discussion is intended to provide a general overview of useful elimination reactions of value in the construction of olefins ∆ ∆ ∆ Review: Lowry & Richardson, Mechanism & Theory in Org. Chem., 3rd Ed, p 588-620 X = O, S ■ Elimination Reactions: The limiting cases + X– +B– E1 family E1cb family –X– (E1 conjugate base) +B – : – –BH –BH rds rds rds E2 family –BH +B– +B– δ – δ – ‡ δ – δ – E1-like TS E2 δ – δ – δ – δ – E1cb-like TS ■ The E2 process encompasses a range of synchronous geometries ■ Why is the anti elimination geometry preferred? For π Bonds: Better than σ C–H HOMO X σ* C–X LUMO σ* C–X LUMO σ C–HY HOMO X H H Better than Anti Geometry Syn Geometry Trost, Ed., Comprehensive Organic Synthesis 1992, Vol 6, Chapter 5.1 Comprehensive Organic Synthesis, 6, Ch 5.1, p 949 Comprehensive Organic Synthesis, 6, Ch 5.1, p 949 Comprehensive Organic Synthesis, 6, Ch 5.3, p 1011 Comprehensive Organic Synthesis, 6, Ch 5.3, p 1011 Comprehensive Organic Synthesis, 6, Ch 5.3, p 1011 Comprehensive Organic Synthesis, 6, Ch 5.3, p 1011 ∆ C H C R2 X C C C C H C C C C C H C X C H C C C X X C X C H B H B C X C C H C X B H B C X R2 R1 R2 H Se R1 R1 R2 O Ar N R O H X R1 R2 R2 R1 R1 H R2 R N R R2 R2 R1 R1 H R R S Ar O R2 R1 R1 H R2 H R R2 R1 R1 X O R2 R1 R2 R1 X H C A B A B C C C C 27A-01-Elimination Rxns 12/7/93 12:00 PM
D. A. Evans Elimination Reactions The e2 Process Chem 11 a Syn E2 elimination can be promoted by steric or torsional factors Some of the Practical Dehydrating Agents ■ The Burgess Reagent Burgess JAcs,1970,92,52245226 NEt3 98:2 Org. Synth. Coll. Vol. VI. 788-791 Brown JACS 1970. 92. 200 ■ The basic process: NMe. Eto <5 ally proceeds via a cis -elim base sunders JACS 1983. 105 3183 Burgess:Acs,1970.92,52245226 a Direction of E2 elimination can be controlled by leaving group Nonbonding interactions disfavor X=Br72:28 X=C|67:33 a Dehydration of 2 and 3 alcohols: Crabbe, JOC, 1970, 35, 2594-2596 X=NMe305:95 1.PhH.25°C 75% 1. MeCN Duncan,JACs,1990,112,8433-8442 27A-02-E2 elimination 12/ 6/93 10: 26 AM
25 → 75 °C exothermic D. A. Evans Elimination Reactions: The E2 Process Chem 115 ■ Syn E2 elimination can be promoted by steric or torsional factors 98 : 2 Brown JACS 1970, 92, 200 RONa + + anti syn base base R1 R2 base % syn Ph Me2CH HO– 69 HO 25 – Ph Me Ph D EtO– <5 Saunders JACS 1983, 105, 3183 ■ Direction of E2 elimination can be controlled by leaving group MeO– X = I 81:19 X Ratio X =Br 72:28 X =Cl 67:33 X =F 30:60 X =NMe3 05:95 + + + HO– HO– Nonbonding interactions disfavor internal elimination (Hoffmann) Some of the Practical Dehydrating Agents ■ The Burgess Reagent: Burgess: JACS, 1970, 92, 5224-5226. Burgess: JOC, 1973, 38, 26-31. Burgess: Org. Synth. Coll. Vol. VI. 788-791 (preparation of the reagent). - + 1 ■ The Basic Process: 1 - + HNEt3 ■ Dehydration usually proceeds via a cis -elimination: - 1 1 - Burgess: JACS, 1970, 92, 5224-5226. ■ Dehydration of 2° and 3° alcohols: Crabbé, JOC, 1970, 35, 2594-2596. 1, PhH, 25 °C 75% 1, MeCN 66% Duncan, JACS, 1990, 112, 8433-8442 Ph Ph H H OH H O S O O Ph Ph N CO2Me Ph D Ph R R H OH H O S O O R R MeO N S NEt3 O O O H Ph Ph D OH D O S O O Ph Ph N CO2Me Ph H H Ph D H D H D H OTs H H D H C C H NMe3 D H R1 R2 C R1 R2 C H D NMe3 H C R2 H C R1 D C R2 C D R1 H X Me Me Me Me Me C H H9C4 C H Me N H Me Me C C H NMe3 C4H9 H H H Me Me Me Me Me Me H HO N CO2Me R H H R Me Me H O O OH Me Me 27A-02-E2 elimination 12/6/93 10:26 AM
D A Evans&D. Bames Elimination Reactions The Burgess Reagent Chem 11 a Primary alcohols are displaced to form the urethane Other uses of the Burgess Reagent a Dehydration of primary amides to form nitriles Burgess: Org. Synth. Coll. Vol. VI. 788-791 a Cationic behavior noted in some instances 3 equiv 1 or Claremont,TL,1988,29,21552158 ue, JCS PT1,1987,1011-1015 I Allylic alcohols can undergo a [3, 3 s opic rearrangement a Cyclodehydration to form oxazolines 1, triglyme, 75 OMe ring closure occurs with inversion 1. THF then 94% JAcs,1992,114,1097510978 P. Wipf JoC,193,58,1575-1578 Tet.Let,1992,33,907 This allylic rearrangement has not been exploited 27A-03-Burgess reagent-2 12/6/93 10: 33 AM
70 °C, 2 h P. Wipf ring closure occurs with inversion ■ Cyclodehydrations to form oxazolines: Westellamide JACS, 1992, 114, 10975-10978 JOC, 1993, 58, 1575-1578 Tet. Let, 1992, 33, 907 ■ Dehydration of primary amides to form nitriles: Other uses of the Burgess Reagent: - + 1 3 equiv 1 82% no dehydration of 2° alcohols observed Claremon, TL, 1988, 29, 2155-2158. This allylic rearrangement has not been exploited McCague, JCS PT1, 1987, 1011-1015 2.8 : 1 1 or ■ Cationic behavior noted in some instances Burgess: JOC, 1973, 38, 26-31. 1) 1, THF then 2) NaH, RT 94% 1, triglyme, 75 °C 73% ■ Allylic alcohols can undergo a [3,3] sigmatropic rearrangement: Burgess: Org. Synth. Coll. Vol. VI. 788-791. 1, 95° 80% ■ Primary alcohols are displaced to form the urethane: D. A. Evans & D. Barnes Elimination Reactions: The Burgess Reagent Chem 115 Me OH Me N H OMe O Me Me OH Me Me Me Ph Me NHCO2Me Ph H HO Et OMe Ph Ph OH Et H MeO Ph Ph OMe Et Ph Et OMe Ph Me O Me S MeO N O O O M Me O Me H OH CONH2 HO Me Me O Me O Me H OH CN HO Me Me O MeO N S NEt3 O O O R H N OMe O O HO Me O R N O OMe Me O N O N H Me Me N O HN Me Me N O NH O Me Me Me Me Me O 27A-03-Burgess reagent-2 12/6/93 10:33 AM
D. A Evans. D M. Bames Elimination Reactions: The martin Sulfurane Chem 11 I Preparation of the Martin Sulfurane OTIPS Martin: Org. Synth. Coll. Vol. VI. 163-166 OC(CF3)2Ph JAcs,1972,94,50035010 0°45 a Dehydrations to form alkenes MsCl, SOCl2, p-chlorobenzoyi chloride, CSA, Burgess Reagent, TFAA/ base Tf2o/ pyridine all ineffective in the dehydration However, 1 alcohols react to give the ether. Evans. Black JACS. 1993. 115. 4497 Meo oMe I Mechanism: Reagent provides both good leaviNg group and moderate base OC(CF3hPh fast NMe NMe HOC(CF3)2Ph Evans,JACs,1978,100,15481557 (±) Cheryline 置 a Rxns with diols generate cyclic ethers: Martin, JACS, 1974, 96, 4604-4611 ZOC(CF3)2Ph ■ Applications i Rxns with amides result in transesterification: Martin, JACS, 1974, 97, 6137 Martin Sulfuran Only product (92%6 Burgess Reagent Snieckus,T,1982,23,1343-1346 27A-04-Martin Sulfurane 12/6/93 10: 20 AM
25°C 98% 1 ■ Rxns with amides result in transesterification: Martin, JACS, 1974, 97, 6137 Elimination Reactions: The Martin Sulfurane 1 ■ Rxns with diols generate cyclic ethers: Martin, JACS, 1974, 96, 4604-4611 1 Evans, JACS, 1978, 100, 1548-1557 1 (±)-Cherylline ■ Applications: 1 Martin Sulfurane: Only product (92%) Burgess Reagent: 1 : 4 Snieckus, TL, 1982, 23, 1343-1346 –OC(CF3)2Ph + + HOC(CF3)2Ph ■ Mechanism: Reagent provides both good leavilng group and moderate base 82% 0 °C 45 min Martin, JACS, 1971, 93, 4327-4329 JACS, 1972, 94, 5003-5010 However, 1° alcohols react to give the ether: 1 1 ■ Dehydrations to form alkenes: Martin: Org. Synth. Coll. Vol. VI. 163-166. ■ Preparation of the Martin Sulfurane: D. A. Evans, D. M. Barnes Chem 115 1 MsCl, SOCl2, p -chlorobenzoyl chloride, CSA, Burgess Reagent, TFAA / base, Tf2O / pyridine all ineffective in the dehydration. Evans, Black, JACS, 1993, 115, 4497 fast 100% 1 25 °C seconds 90:10 R R S OC(CF3)2Ph OH OC(CF3)2Ph Ph Ph R R Me OH Me Me Me Me OH Me CH2 OH R R S Ph Ph OC(CF3)2Ph OC(CF3)2Ph R R O S Ph OR S Ph H O Ph Ph R R R R HO Me Me Me Me CONMe2 Me Me Me Me CONMe2 Me CONMe2 Me Me NMe OH MeO OMe MeO O BnO OH NMe MeO OMe MeO O BnO NMe MeO HO Ph N H Me O O Ph CF O 3 CF3Ph Me Me HO Cl R OH Me O Cl Me Me OH O Et HO H O H H H OTBS OTIPS Me O OH H H O Et O O H H H OTBS OTIPS Me O H H Me Me O CF3 CF3 Ph 27A-04-MartinSulfurane 12/6/93 10:20 AM
D H Ripin& D A. Evans Elimination reactions of selenoxides Chem 115 The selenoxide elimination reaction The first example: Jones, Chem. Commun 1970, 86. General Selenium References elenium in Natural Products Synthesis, K C Nicolaou, N. A Petasis Organoselenium Chemistry, D. Liotta, 1987 Wiley-Interscience Selenium Reagents and Intermediates in Organic Synthesis, C. Paulmier @1986 Pergamon Press Functionalization of olefins 20°C→40°C PhSe-X -PhSeoH By comparison X=OAC OH. CN. CL Br 80c→130°c Sharpless, J. Org. Chem. 1974, 39, 429 州H| PhSOH The selenoxide elimination is usually two ste A. Selinide formation Nucleophilic Selenium Reagents RSeCN or RSe SeR and NaBH4, RSeM, RSeH (with Lewis Acid) Chapter 4, Organoselenium Chemistry, D. Liotta, 1987 Wiley-Interscience Electrophilic Selenium Reagents Tomoda. Chem. Commun 1982, 871; Tet. Lett 1982, 23, 1361 RSeCl, RSeBr, RSe(O)Cl, RSeSeR, alkyl selenium succinimide, RSeSO2Ar Chapter 1, Organoselenium Chemistry, D. Liotta, 1987 Wiley-Interscience Epoxide Ring Opening-Refunctionalization a Some useful oxidizing agents H202, MCPBA, RCOOOH, NaIO4, O3,(t-BuO)2, Th" Nitrate, NCS or NBS/H20 PhSe-SePh Chapter 5, Selenium Reagents and Intermediates in Organic Synthesis, C Paulmier, 1986 Pergamon Press 27A-05-Selenoxide elim-1 12/6/93 11: 00 AM Both of the above reactions have been heavily exploited in synthesis
Tomoda, Chem. Commun 1982, 871; Tet. Lett 1982, 23, 1361 PhSeCN ∆ [Ox] ■ Functionalization of Olefins: Sharpless, J. Org. Chem. 1974, 39, 429. 3 <1 2 49 97 99 98 51 OAc OH OMe Cl Chapter 5, Selenium Reagents and Intermediates in Organic Synthesis, C. Paulmier,1986 Pergamon Press. Chapter 4, Organoselenium Chemistry, D. Liotta, 1987 Wiley-Interscience. RSeCN or RSeSeR and NaBH4, RSe-M+, RSeH (with Lewis Acid) Chapter 1, Organoselenium Chemistry, D. Liotta, 1987 Wiley-Interscience. RSeCl, RSeBr, RSe(O)Cl, RSeSeR, alkyl selenium succinimide, RSeSO2Ar, ... H2O2, MCPBA, RCOOOH, NaIO4,, O3, (t-BuO)2, ThIIINitrate, NCS or NBS/H2O ■ Some useful oxidizing agents: ■ Electrophilic Selenium Reagents: ■ Nucleophilic Selenium Reagents: The selenoxide elimination is usually two steps: A. Selinide formation B. Oxidation & elimination. Selenium in Natural Products Synthesis, K. C. Nicolaou, N. A. Petasis Organoselenium Chemistry, D. Liotta, 1987 Wiley-Interscience. Selenium Reagents and Intermediates in Organic Synthesis, C. Paulmier, © 1986 Pergamon Press. General Selenium References: -20˚C → 40˚C D. H. Ripin & D. A. Evans Elimination Reactions of Selenoxides Chem 115 + The Selenoxide Elimination Reaction + ‡ By comparison: ‡ + + 80 ˚C → 130˚C -PhSeOH -PhSOH 20˚C The first example: Jones, Chem. Commun 1970, 86. O3 + PhSe–X [Ox] ∆ X Ratio X = OAc, OH, CN, Cl, Br, + X– ■ Epoxide Ring Opening-Refunctionalization: PhSe–SePh NaBH4 [Ox] Both of the above reactions have been heavily exploited in synthesis SePh CN Me Se H H Se Me Se–Ph Me H Ph–Se H R R H H O– R H H R X X Ph H H Ph OXSePh O SePh OH OH Se O H H R R H Ph S Ph H O R R H H R H H R Ph–S O– H H R R H CN 27A-05-Selenoxide elim-1 12/6/93 11:00 AM
D H Ripin& D A. Evans Elimination reactions of selenoxides Chem 115 Synthetic Applications Functionalization of olefins. Ph PhSecl 0°C OTBS i Phse cf(omer Raucher Tet. Lett. 1979. 3057 Me Seph cI H202 OTBS This is kinetic product at BF3oEt2 Aco PhseOH NaHco CoH13 SePh [Ox Raucher. Tet Lett 1977. 3909 PhSe-sO2Ph SOpH Rollin Synthesis 1984, 134 SePh These ns are quite valuable in setting up Claisen rearrangements Mooch OTBDPS 25℃c DBU, xylene,↑↓ EtO2C OTBDP Metz. Tet Lett 1982. 23. 4067 (+)-Laurencin Holmes j Am. chem. soc. 1993. 115 10400 27A-06-Selenoxide elim-2 127/93 12: 02 PM
free radical addn Rollin Synthesis 1984, 134. ∆ NaIO4 NaHCO3 83% 85% BF3OEt2 55% [Ox] Raucher Tet. Lett. 1979, 3057. H+ steps 25 °C DBU, xylene, ↑↓ Holmes J. Am. Chem. Soc. 1993, 115, 10400. NaIO4 NaHCO3 73% (+)-Laurencin Metz, Tet. Lett 1982, 23, 4067 [Ox] ∆ PhSeBr CH2=CHOEt hν PhSe-SO2Ph ∆ [Ox] Kice, Tet. Lett 1980, 21, 4155 Raucher, Tet. Lett 1977, 3909 [Ox] ∆ PhSeBr MeCN This is kinetic product at lower temperatures Beau, JACS, 1983, 105, 621 pyr H2O2 Cl– 0 °C PhSeCl ■ Functionalization of Olefins: + Synthetic Applications D. H. Ripin & D. A. Evans Elimination Reactions of Selenoxides Chem 115 These rxns are quite valuable in setting up Claisen rearrangements O O OTBDPS SePh O O OTBDPS H OAc O Et Br H OTBDPS O O OH Me CO2Me Me PhSe C(OMe)3 SePh Me Me Me OTBS OTBS Me CO2Me O OAc AcO AcO PhSe OH AcO AcO O O SePh O O AcO AcO AcO AcO O Me SePh Cl SePh Me OTBS Me Me OTBS Me Br Cl SePh C6H13 C6H13 C6H13 SePh Br SO2Ph Ph Ph Ph SO2Ph OH H MeOCH2 Br OEt PhSe MeOCH2 H O OEt SePh EtO2C CHO H MeOCH2 27A-06-Selenoxide elim-2 12/7/93 12:02 PM
D H Ripin& D A. Evans Elimination reactions of selenoxides Chem 115 Epoxide Cleavage/Refunctionalization H2O2 THPO THPO Seph Reich J. Am. Chem. Soc. 1973. 95. 5813 Grieco J. Org. Chem. 1975, 40, 542 lycoricidine Ohta. Tet. Lett 1975. 2279 H202 PhaSe Sharpless, Tet. Lett. 1973, 1979 b)H202, THF, 0'C Medoc Grieco J. Org. Chem. 1975, 40, 1450 Ph2Se2l MCPBA OTMS steps SePh different mechanism for elimination H Kowakski JACS 1980. 102. 7950 Clive joc1982,47,1632 27A-07-Selenoxide elim-3 12/6/93 1: 10 PM Tsuda. Chem. Commun 1975. 933
Clive JOC 1982, 47, 1632. Kowakski JACS 1980, 102, 7950. Note the different mechanism for elimination in this case MsCl/Et ZnCl2 3N b) H2O2, THF, 0˚C o-O2NC6H4SeCN NaBH4, 20˚C 59% Grieco J. Org. Chem. 1975, 40, 1450. H2O2 3 : 1 Sharpless, Tet. Lett. 1973, 1979. H2O2 69% H2O2 4 : 1 Reich J. Am. Chem. Soc. 1973, 95, 5813. 9 : 1 Grieco J. Org. Chem. 1975, 40, 542. D. H. Ripin & D. A. Evans Elimination Reactions of Selenoxides Chem 115 ■ Epoxide Cleavage/Refunctionalization: Ph2Se2 NaBH4 H2O2 63% steps lycoricidine Ohta, Tet. Lett 1975, 2279 NaBH4 Ph2Se2 NaIO4 70% Ac2O Ph2Se2 MCPBA NaBH4 NaIO4 steps lycorine Tsuda, Chem. Commun 1975, 933 NH O O O THPO THPO OH SePh O O NH NH O O OH THPO OH O O Me O Me SePh Me O Me NH OH O O OH O O N H H H H N Me O O Me H SePh H O O H O O H H O Me Me PhSe H Me Ph Me H Ph Me Ph Me Me OMe MeOOC MsO MeOOC OMe OTMS Me SePh O H O O O O HO SePh H HO O O O N H H H N O O O AcO O OH H AcO O O O N H N O O HO OH Me SePh OH Me O 27A-07-Selenoxide elim-3 12/6/93 1:10 PM
D. A. Evans Cheletropic Elimination Reactions Chem 11 The Ramburg-Backluind Reaction I Acyclic Olefin Synthesis (B(2)>97:3 DMSO HO2C、C X= halogen, tosylate, triflate ag naOH HC (B:(z=21:79 Reviews Scholz, Liebigs Ann. Chem. 1984, 264 Paquette, Organic Reactions 1977, 25, 1 0 Olefin geometry dependent upon reaction conditions Magnus, Tetrahedron 1977, 33, 2019 o Strong base(tBuOK) equilibrates episulfone intermediate to Vedejs Tetrahedron 1982, 38, 285 thermodynamically favored trans configuration giving(Er-olefir Trost, Ed, Comprehensive Organic Synthesis 1992, Vol 3, Ch 3.8. General Reaction Protocol a Vinylogous Ramberg- Backlund Reaction Effects the transformation of alkenes to 1.3-dienes 丫冷 NaoMe 0H.△ BrCH2SO, Br CH2 Ch, hv Meyers' Modification alkene BUOH.A- PhPh Meyers, JACS,91, 7510 Modified procedure allows one-pot conversion of sulfone to olefin eaction of ing olefin with dichlorocarbene generated in strongly (E(z)=1783 (E(z)=10:1 basic chlorinating medium can sometimes complicate reaction KOH, CCl4 61% 日x(z=946 65% Block,JACS1983,105,6164,6165 27A-08-Ramberg-Backlund Rxn 12/6/93 1: 11 PM
Effects the transformation of alkenes to 1,3-dienes. (E):(Z) = 94:6 tBuOK tBuOH, ∆ 1,3-diene alkene (E):(Z) = 17:83 tBuOH, ∆ tBuOK DBU CH2Cl2, hν BrCH2SO2Br (E):(Z) = 10:1 ■ Vinylogous Ramberg-Backlünd Reaction ■ Reviews Modified procedure allows one-pot conversion of sulfone to olefin. Reaction of resulting olefin with dichlorocarbene generated in strongly basic chlorinating medium can sometimes complicate reaction: tBuOH, ∆ KOH, CCl4 D. A. Evans Cheletropic Elimination Reactions Chem 115 Block, JACS 1983, 105, 6164, 6165. ■ Acyclic Olefin Synthesis t-BuOK DMSO (E):(Z) > 97:3 (E):(Z) = 21:79 aq NaOH ∆ ❐ Olefin geometry dependent upon reaction conditions. The Ramburg-Backlünd Reaction Base ■ General Reaction Protocol NaH NCS or C2Cl6 NaOMe MeOH, ∆ Meyers' Modification: X = halogen, tosylate, triflate Paquette, Organic Reactions 1977, 25, 1. Magnus, Tetrahedron 1977, 33, 2019. Vedejs, Tetrahedron 1982, 38, 2857. Trost, Ed., Comprehensive Organic Synthesis 1992, Vol 3, Ch 3.8. Meyers, JACS 1969, 91, 7510 KOH, CCl4 tBuOH, ∆ + 35% 65% 97% 66% Scholz, Liebigs Ann. Chem. 1984, 264. ❐ Strong base (tBuOK) equilibrates episulfone intermediate to thermodynamically favored trans configuration giving (E)-olefins. (Z)-vinylogous sulfones yield opposite olefin geometry (trans): 59% 61% base X Ph S R O O O S O O O R Ph Cl Ph O R1 S R2 R O O Ph Ph S Ph O O Ph nC5H11 nC4H9 S Br O O Br S R1 R2 O O R1 R2 HO Cl 2C S Et O O Et S O O Br HO2C HO2C Et nC4H9 nC4H9 nC4H9 S Br O O nC4H9 S O O Cl Cl S O O R1 R2 R1 R2 27A-08-Ramberg-Backlund Rxn 12/6/93 1:11 PM
D. A. Evans. S. Nelson Cheletropic Elimination Reactions Chem 11 Applications to Synthesis I Enediyne Synthesis: Calicheamicin /Esperamicin Models I Strained Ring Systems Intraannular Ramberg-Backlund reactions succeed where many annulation procedures fail in producing highly strained tBuOK 35-49% 32-52% 75° C to rt Nicolaou, JACS 1992, 114. 7360 Becker. Hel. Chim. Acta 1983. 66. 1090 Neocarzinostatin Chromophore: A Related Reaction =>= mCPB Wender. Tet. Lett. 1988. 29 909 t BuOK Cheletropic elimination occurs with o rather than t-bond formation E20,0°c ■ Eremantholide a Gassman. JACS 1983. 105. 667. ■ Deuterated olefins NaoD HMPA. DME 85% 81% Acidity of a-methylene groups provides ready access to deuterated olefins via the Ramberg- Backlund reaction Boeckman, JACS 1991. 113 9682. If cheletropic elimination is sufficiently slow, dehydrohalogenation can compete variety of annulation procedures for direct 9-member ring formation eidlein, Leibigs Ann. Chim. 1980, 1 27A-09-Ramberg Applications 12/7/93 12: 04 PM
A wide variety of annulation procedures for direct 9-member ring formation were unsuccessful. Boeckman, JACS 1991, 113, 9682. 85% 82% Eremantholide A ■ Eremantholide A 9-15% Wender, Tet. Lett. 1988, 29, 909. Cheletropic elimination occurs with σ rather than π-bond formation. PhH/CH3CN Ph2CO, hν ■ Neocarzinostatin Chromophore: A Related Reaction Nicolaou, JACS 1992, 114, 7360. 32-52% Neidlein, Leibigs Ann. Chim. 1980,1540. If cheletropic elimination is sufficiently slow, dehydrohalogenation can compete. Base Paquette, JACS 1974, 96, 5801. 81% ■ Deuterated Olefins 18% Gassman, JACS 1983, 105, 667. 35-49% Intraannular Ramberg-Backlünd reactions succeed where many annulation procedures fail in producing highly strained ring systems. D. A. Evans, S. Nelson Cheletropic Elimination Reactions Chem 115 Becker, Helv. Chim. Acta 1983, 66, 1090. ■ Enediyne Synthesis: Calicheamicin/Esperamicin Models Applications to Synthesis ■ Strained Ring Systems tBuOK, THF -75 °C to rt NaOD D2O ∆ tBuOK, THF Acidity of α-methylene groups provides ready access to deuterated olefins via the Ramberg-Backlünd reaction. Na2S 1) NCS, CCl4 2) mCPBA tBuOK Et2O, 0 °C n tBuOK THF, -78 °C n n = 3-8 Et3COK HMPA, DME ∆ H3O+ S O O Br SO2 O2S (CH2) Cl Cl (CH2) O O O2S O Me H O Me Me O Me Cl O Me Me O H Me D D Cl SO2 D D D H H S OTs TsO H H H H O2S Cl H H O Me O O O O Me O Me H O Me Me O OH SO2 SO2 H H Cl HO SO2 Me HO Me 27A-09-Ramberg Applications 12/7/93 12:04 PM