Sarah Siska. C. A. Morales Felkin-2 Chem 206 Felkin: Accounting for Less Selective Reactions Weaknesses in Felkins Argument 1)The t-butyl ketone case 1)Polar effect with a-branching, in any staggered conformation, syn-pentane is impossible to avoid main repulsion to minimize between Nu and electronegative group X le xre no justification given Rs 2)Breakdown for aldehydes 2) Transition states for minor products(does not consider conformers without ketone R, important steric interaction removed with Rl next to R) would predict RM to be next to H rather than carbonyl Rs possible for wrong prediction when RM is+Ry small sma Anh's Solutions RL 1)Antiperiplanar effect 3)2-methylcyclohexanone best acceptor o* orbital aligned parallel to t and*c=0+0c-x cannot adopt Felkin-type conformation; still considered as a reactant-like orbitals of carbonyl n地ucx transition state stabilization of incoming selectivity based on competition between torsional strain and steric 2)Non-perpendicular attack ation of the bur Anh. N. T: Eisenstein. O Nouv. J. Chim. 1977. 1. 61 Burgi, H.B∴Dunt,J.D (CH steric strain (small Nur 1973,955065 igi, H. B; Dunitz, J. D Tetrahedron 1974. 30. 1563 Cherest, M. Felkin, H. Prudent, N. Tetrahedron Lett. 1968. 18, 2199: 2205 favored disfavoredRL RS RM M O R RM RL RS M O R (CH2)4 (CH2)4 O Me H Nu: Nu: O Cy t-Bu Me O Me LAH LiAlH4 Me t-Bu Cy OH 1.6 Me OH t-Bu Cy Me OH 1 Me OH H O Me RL RS RM Me Me Me O Felkin: Accounting for Less Selective Reactions 1) The t-butyl ketone case • cannot adopt Felkin-type conformation; still considered as a reactant-like transition state • selectivity based on competition between torsional strain and steric strain possible when RM is relatively small torsional strain (large Nu:) steric strain (small Nu:) + : Sarah Siska, C. A. Morales Felkin-2 Chem 206 major Nu: • with a-branching, in any staggered conformation, syn-pentane is impossible to avoid 2) Transition states for minor products (does not consider conformers with RL next to R) 3) 2-methylcyclohexanone possible for small nucleophiles + Chérest, M.; Felkin, H.; Prudent, N. Tetrahedron Lett. 1968, 18, 2199; 2205 RL RS RM M O H RL RS RM M O H RL RS RM H O M Nu: Nu: Nu: X RS RM/L R O M O X RM/L RS H M Anh, N. T.; Eisenstein, O. Nouv. J. Chim. 1977, 1, 61 Bürgi, H. B.; Dunitz, J. D.; Shefter, E. J. Am. Chem. Soc. 1973, 95, 5065 Bürgi, H. B.; Dunitz, J. D.; Lehn, J. M.; Wipff, G. Tetrahedron 1974, 30, 1563 Weaknesses in Felkin's Argument Nu: • main repulsion to minimize between Nu and electronegative group X -- no justification given 1) Polar effect 2) Breakdown for aldehydes wrong prediction Anh's Solutions 1) Antiperiplanar effect • best acceptor s* orbital aligned parallel to p and p* orbitals of carbonyl; stabilization of incoming anion pC=O ↔ s*C-X nNu ↔ s*C-X • without ketone R, important steric interaction removed: would predict RM to be next to H rather than carbonyl 2) Non-perpendicular attack • incorporation of the Bürgi-Dunitz trajectory favored disfavored Nu