Nucleophilic Additions to Fused Bicyclic Five-Membered Ring Oxocarbenium Ions:  Evidence for Preferential Attack on the Inside Face

• Published in: Journal of the American Chemical Society Vol. 125; no. 46; pp. 14149 - 14152
• Main Authors: Smith, Deborah M, Tran, Michelle B, Woerpel, K. A
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 19.11.2003; Amer Chemical Soc
• Subjects: Acetals - chemistry; Bridged Bicyclo Compounds, Heterocyclic - chemistry; Chemical reactivity; Chemistry; Chemistry, Multidisciplinary; Ethers, Cyclic - chemistry; Exact sciences and technology; Furans - chemistry; Molecular Conformation; Organic chemistry; Physical Sciences; Reactivity and mechanisms; Science & Technology; SUBSTITUTION; DISUBSTITUTED TETRAHYDROFURAN DERIVATIVES; ETHERS; EXTENSIONS; STEREOCHEMISTRY; CONSTRUCTION; GAMMA-LACTOLS; ACETALS; ALLYLSILANES; MOIETIES; Stereoselectivity; Five membered ring; Carbenium compounds; Furan derivatives; Experimental study; Oxygen heterocycle; Nucleophilic substitution; Nucleophilic addition
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja0375176

Evidence is provided that nucleophilic attack on five-membered ring oxocarbenium ions occurs from the inside face of the envelope. An eight-five fused-bicyclic system in which two substituents are constrained to pseudoequatorial positions underwent nucleophilic addition with selectivity that was comparable to an unconstrained monocyclic system. On the other hand, a bicyclic six-five analogue underwent reaction with low selectivity. This observation indicates that minimization of eclipsing interactions by attacking inside the envelope is not enough to control selectivity, but that the changes in the overall three-dimensional structure of the ring must be favorable as well. In the bicyclic six-five series, the six-membered ring is accommodated in the cation, but it destabilizes the transition state structure leading to the first-formed product of inside attack.