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