D A Evans, J. Johnson Rules for Ring closure: SP Carbon Related Systems Chem 206 Endo Digonal versus Endo Trigonal Cyclizations Indole synthesis CHaR 5-endo-trig R=Me, Bu, CO, Me LiTMP Out-of-plane approach nucleophile lone pair is nucleophile lone pair can't Saegusa, J. Am. Chem. Soc. 1977, 99, 3532 rthogonal to t achieve Burgi-Dunitz angle 5-endo-dig I Spiro dihydrofuranones Allowed due to in-plane pi orbitals KOBu For an opposing viewpoint to Baldwin's view of nucleophile trajectories, see Developing negative charge on the central allenic carbon is Menger's article on directionality in solution organic chemist in the same plane as the oMe group Tetrahedron 1983. 39. 1013 Magnus, J Am. Chem. Soc. 1978, 100, 7746 MeOH 5-endo-dig NaOMe 5-endo-trig however, the acid catalyzed version does cyclize 4-endo-dig win. J. Chem. Soc. Chem. Commun. 1976. 736 4928:909236D. A. Evans, J. Johnson Rules for Ring Closure: SP Carbon & Related Systems Chem 206 Endo Digonal versus Endo Trigonal Cyclizations 5-endo-trig In-plane approach; nucleophile lone pair is Out-of-plane approach; nucleophile lone pair can't achieve Bürgi-Dunitz angle X: Y orthogonal to p* Y :X Allowed due to in-plane pi orbitals For an opposing viewpoint to Baldwin's view of nucleophile trajectories, see Menger's article on directionality in solution organic chemistry: Tetrahedron 1983, 39, 1013. 5-endo-dig OH O R O O R 5-endo-trig R = H, OMe 5-endo-dig HO O Ph Me Me O Me Me Ph O NaOMe MeOH however, the acid catalyzed version does cyclize Baldwin, J. Chem. Soc., Chem. Commun., 1976, 736. Johnson, Can. J. Chem. 1990, 68, 1780 J. Am. Chem. Soc. 1983, 105, 5090 J. Chem. Soc., Chem. Commun. 1982, 36. CH3 N + C - CH2R N + C - N R 2 equiv. LDA 2 equiv. RX -78 oC R = Me, Bu, CO2Me LiTMP O _ HO OMe O OMe Saegusa, J. Am. Chem. Soc. 1977, 99, 3532. ■ Indole synthesis: ■ Spiro dihydrofuranones: n n Li MeO n KOtBu Developing negative charge on the central allenic carbon is in the same plane as the OMe group Magnus, J. Am. Chem. Soc. 1978, 100, 7746. n = 1,2 4-endo-dig 5-exo-dig Li Ph Ph Li Li Ph Li Ph X X X NaOMe Li+