D. A. Evans reland Enolate Claisen Rearrangement Chem 206 Ireland-Enolate Claisen Substituted enolates afford an additional stereocenter a Reviews Pereira. Aldrichimica Acta 1993. 26.17-29 Ireland. Aldrichimica Acta 1988. 21 59-69 Ireland, R. E: Mueller, R. H: Willard, A. K.J. Am. Chem. Soc. 1976. 98, 2868 OTBS OTBS conditions(E)-( z control 12(320c)=35h LDA. TBSCI LDA, TBSCI 94: 6 kinetic 7 93 thermo Enolization: Amide bases R2 Stereoelectronic Requirements: The a-CH bond must be able to erlap withπ*C-O OTB key study: Ireland, JOC 1991, 56, 650 and earlier cited papers 兀*C-0 Hc\hb R Double Claisen Rearrangements are also possible Paterson, Tet Lett 1991, 32, 7601 avored 日 LDA TMSC LM-Nr, disfavored 1,2 1, 5 syn relationship via The Ireland model 976,98,286 a、(地地了8y 981.22,4119 more recent study. 0c1991,56,650Me R2 R1 OTBS O O OTBS R2 R1 Me O O R2 R1 Me O Et OEt N R R H H R Li O Me N R R H Me R Li O H ✽ ✽ ✽ O O Me O OTMS R O Me Hc Hb Ha R C O Hc Hb R O – OLi R Me R Me OLi OH O O Me Me OH OH Me Me Me Me Me Me O RO OR Me Me O O Me H OTBS H H R1 O R2 R2 H O R1 H OTBS Me H Me Me O O Me Me O Me Me O O R2 R1 OTBS O Me Me O OTBS R2 R1 OTBS OTBS Me O Me O O Me Me Me Me Ireland-Enolate Claisen Ireland, R. E.; Mueller, R. H.; Willard, A. K. J. Am. Chem. Soc. 1976, 98, 2868 LDA Me3SiCl t1/2 (32oC) = 3.5 h 66% ■ Reviews Pereira, Aldrichimica Acta 1993, 26, 17-29 (Ireland-Claisen) Ireland, Aldrichimica Acta 1988, 21, 59-69 (Claisen-related) D. A. Evans Ireland Enolate Claisen Rearrangement Chem 206 ■ Enolization: Amide Bases LM–NR2 ‡ (E) Geometry (Z) Geometry The Ireland Model (JACS 1976, 98, 2868) Narula, Tetrahedron Lett. 1981, 22, 4119 more recent study: Ireland, JOC 1991, 56, 650 Substituted enolates afford an additional stereocenter LDA, TBSCl LDA, TBSCl DMPU ✽ (E) (Z) conditions (E):(Z) LDA, TBSCl LDA, TBSCl DMPU 94:6 7:93 key study: Ireland, JOC 1991, 56, 650 and earlier cited papers Stereoelectronic Requirements: The a-C-H bond must be able to overlap with p* C–O – Ha + base p* C–O Paterson, Tet Lett 1991, 32, 7601 LDA, TMSCl Et3N 20-60 °C 1,2 syn aldol relation permuted into 1,5 syn relationship via Claisen rearrangement 63% yield (diastereoselection 86%) Double Claisen Rearrangements are also possible ‡ ‡ favored disfavored control kinetic thermo