D. A. Evans SN2 Reaction: Stereoelectronic Effects Chem 206 The reaction under discussion: The use of isotope labels to probe mechanism. i 1 and 2 containing deuterium labels either on the aromatic ring or on the methyl group were prepared. A 1: 1-mixture of 1 and 2 were allowed to react a If the rxn was exclusively intramolecular, the products would only contain only three deuterium atoms a The Nu-C-x bonding interaction is that of a 3-center, 4-electron bond. The frontier orbitals which are involved are the nonbonding orbital from ell as CD3-Ar-Nu- gC-X and o+C-X H3C a If the reaction was exclusively intermolecular, products would only contain I Experiments have been designed to probe inherent requirement for achieving possilbilier'3e №-C--X RCHrx differing amounts of D-label depending on which two partners underwent reaction. The deuterium content might be analyzed by mass spectrometry. Here are the a 180Nu-C-X bond angle: Here both Nu and leaving group are constrained to D3-product 2 CD3-Ar-NL-CH3 be part of the same ring 2+2 D'3-product 2 CH3-Ar-NU--CD 1+2 Do-product 1 CD3-Ar-NU-CD3 №u- Hence, for the strictly intermolecular situation one should see the following ratios Do:D3:D3:D6=1:2:2:1 tethered reactants constrained transition state The product isotope distribution in the Eschenmoser expt was found to b exclusively that derived from the intermolecular pathway The Eschenmoser Experiment(1970): He/v Chim Acta 1970, 53, 2059 Other Cases a The reaction illustrated below proceeds exclusively through bimolecular pathway exclusive rcH~80→(a~s0 in contrast to the apparent availability of the intramolecular path 16‰ intramolecular SO3CH3 84% intermolecular Hence, the Nul-C-x 180 transition state bond angle must be rigidly maintained for the reaction to take placeD. A. Evans SN2 Reaction: Stereoelectronic Effects Chem 206 d– d– ‡ Nu: – X: – The reaction under discussion: ■ The Nu–C–X bonding interaction is that of a 3-center, 4-electron bond. The frontier orbitals which are involved are the nonbonding orbital from Nu as well as sC–X and s*C–X: s *C–X sC–X Nu: – d– d– energy ■ Experiments have been designed to probe inherent requirement for achieving a 180 ° Nu–C–X bond angle: Here both Nu and leaving group are constrained to be part of the same ring. d– d– "tethered reactants" "constrained transition state" Nu: – – – ■ The reaction illustrated below proceeds exclusively through bimolecular pathway in contrast to the apparent availability of the intramolecular path. 1 2 1 and 2 containing deuterium labels either on the aromatic ring or on the methyl group were prepared. A 1:1-mixture of 1 and 2 were allowed to react. ■ If the rxn was exclusively intramolecular, the products would only contain only three deuterium atoms: exclusively intramolecular exclusively intramolecular The use of isotope labels to probe mechanism. ■ If the reaction was exclusively intermolecular, products would only contain differing amounts of D-label depending on which two partners underwent reaction. The deuterium content might be analyzed by mass spectrometry. Here are the possibilities: 1 + 1 D3 -product D'3 2 + 2 -product D6 -product 1 + 2 D0 -product 2 CD3–Ar–Nu–CH3 2 CH3–Ar–Nu–CD3 (CD3–Ar–Nu–CH3 ) (CH3–Ar–Nu– CD3 ) 1 CD3–Ar–Nu–CD3 1 CH3–Ar–Nu–CH3 Hence, for the strictly intermolecular situation one should see the following ratios D0 : D3 : D'3 : D6 = 1 : 2 : 2 : 1. The product isotope distribution in the Eschenmoser expt was found to be exclusively that derived from the intermolecular pathway! + – exclusively intermolecular + – 16% intramolecular 84% intermolecular – – – – Other Cases: The Eschenmoser Experiment (1970): Helv. Chim Acta 1970, 53, 2059 C X R H H C H H R Nu X C H H R Nu Nu C X Nu C X R H H C X R H H Nu: S O CH3 O O Nu CH3 SO3 Nu: S O CH3 O O Nu CH3 SO3 Nu SO3 CD3 S O O O CD3 Nu: (CH3 )2N SO3CH3 SO3 (CH3 )3N SO3CH3 N(CH3 )2 N(CH3 )3 SO3 D3C H3C H3C D3C Hence, the Nu–C–X 180 ° transition state bond angle must be rigidly maintained for the reaction to take place. RCH2–X