u Acomplete tumover in olefin diastereofacial selectivity is bserved when adding intemal and extemal nucleophiles Hehre's Analysis 人一 Addition product cis trans 95:5 Nu ti99:1 Favored ground. l2 General observation Disfavored a-complex Favored iodonium ion the major diastereomer from electrophile-induced cyclization is opp observed in the analogous intermolecular electrophilic addition. For a review of eletrophilic induced olefin cyclization reactions see Cardillo M. Orena. Tetrahedron 1990. 46. 3321 Chamberlin& Hehre s Rationalization More reactive ground-sta vred-comp杷ex I"Facial preferences in electrophilic addition reactions are not invariant with respect to the location of the transition state along the reac a Change in diastereoselectivity is a consequence of a change in the rate-limiting step O Addition reactions: Formation of an onium ion intermediate sequently trapped by a Nu from the medium) e Cyclization reactions: Intramolecular attack on a t-complex(not an onium ion) I Analysis of the stereoselectivity of electrophilic addition to chiral olefins 1. Relative abundances of conformational minima 2. Relative reactivities of the available form Houk: Argument for the inside alkoxy effect" in T-complex formation 3. Stereoselectivies of the individual conformers I I-complex cyclizes if R contains a Nu and its formation is rate determining Chamberlin& Hehre, J. Am. Chem. Soc. 1987, 109, 672-677.i Onium ion formation is rate determing in the addition reactions Seminar I The presence or absence of an intemal nucleophile acts to determine the Synthetic and Mechanistic Review of Electrophilic Haloge 1992 ereochemical outcome of the reaction by modifying the nature(timing)of ansition state 10A-05-lodolact/Hehre 10/8/00 8: 12 PM■ "The presence or absence of an internal nucleophile acts to determine the stereochemical outcome of the reaction by modifying the nature (timing) of transition state. ■ Onium ion formation is rate determing in the addition reactions ■ π–complex cyclizes if R contains a Nu and its formation is rate determining For a review of the halogenation reaction see: Andy Ratz, Evans Group Seminar, Synthetic and Mechanistic Review of Electrophilic Halogenation, May 7, 1992. For a review of elctrophilic induced olefin cyclization reactions see: G. Cardillo & M. Orena, Tetrahedron 1990, 46, 3321. ■ "Facial preferences in electrophilic addition reactions are not invariant with respect to the location of the transition state along the reaction coordinate." Chamberlin & Hehre, J. Am. Chem. Soc. 1987, 109, 672-677. - I2 I2 OH2 cis : trans 95 : 5 ratio 99 : 1 I2 I2 H2O ■ A complete turnover in olefin diastereofacial selectivity is observed when adding internal and external nucleophiles Chamberlin & Hehre's Rationalization For electrophiles that react via onium intermediates (I2, Br2, Hg(OAc)2, PhSeCl), the major diastereomer from electrophile-induced cyclization is opposite to that observed in the analogous intermolecular electrophilic addition. General Observation: ■ Analysis of the stereoselectivity of electrophilic addition to chiral olefins: 1. Relative abundances of conformational minima 2. Relative reactivities of the available forms 3. Stereoselectivies of the individual conformers ■ Change in diastereoselectivity is a consequence of a change in the rate-limiting step ● Addition reactions: Formation of an onium ion intermediate (subsequently trapped by a Nu from the medium) ● Cyclization reactions: Intramolecular attack on a π–complex (not an onium ion) + + Nu Nu Disfavored π–complex Favored π–complex Disfavored iodonium ion Favored iodonium ion Cyclization product Addition product Favored ground￾state conformer More reactive ground-state conformer Hehre's Analysis Houk: Argument for the "inside alkoxy effect" in π–complex formation O O HO OH Bu Me OH I Me I H I OH Bu Me OH H I Me HO O O Bu H HO OH Bu Me Me OH HO O O O Me OH H I2 H O O H H R H OH Me Me OH H R H I HO Me Me I H OH Bu Me OH I Me H R HO H H H H H H HO R H Me Me H R HO H H H H OH H R Me I I2 10A-05-Iodolact/Hehre 10/8/00 8:12 PM