A Computational Study of Radical Haloacetal Cyclizations Controlled by the Acetal Center

Abstract

The stereochemical outcome of the radical haloacetal cyclization reaction (Ueno-Stork reaction) has been examined by ab initio and other molecular orbital techniques. It was found that the stereochemistry of 5-exo- and 6-exo trig cyclizations can be accurately predicted from calculations using moderate levels of theory (UHF/6-311G** or B3LYP/6-311G**). A simplified computational procedure, easily run on a standard desktop computer, has been developed that provides excellent predictive ability for the stereochemical outcome for the reactions in question. Interestingly, a novel twist transition state has been identified for the first time in 5-exo-trig radical cyclization reactions.

Diastereoselective Radical‐Mediated Hydrogen‐Atom Abstraction

“…The stereochemistry of the hydrogen‐atom abstraction is best explained by the chairlike model F depicted in Scheme . This model closely parallels model G , which has been proposed based on experimental results and ab initio calculations for the Ueno–Stork cyclization reaction 12. The 2‐methoxy group occupies an axial position as a result of the anomeric effect, and the nonreacting group at C5 is in a pseudoequatorial position.…”

Ni‐Catalyzed Cascade Cyclization–Kumada Alkyl–Alkyl Cross‐Coupling

“…Regarding the cascade cyclization–coupling reaction, we calculated the activation and reaction energy for the cyclization of the secondary radical resulting from a model iodoketal ( V , Figure 2)15 and compared it with the coordination of this radical with Ni II complex II . We were pleased to find that 5‐exo radical cyclization is both faster and more favorable compared with radical coordination to form complex VI .…”

Synthesis of enantiopure (2R)-configured muscarine alkaloids via selective alkoxyl radical ring-closure reactions

“…35 A similar arrangement has recently been located as lowest energy transition structure in ab initio calculations dealing with 5-exo-trig cyclizations of anomeric carbon radicals. 39 Geometry twist-I, which probably reflects substituent effects onto the conformational behavior of such energetically favored transition structures more adequately, transposes the benzoyloxy and the methyl group into equatorial positions whereas the methylene end of the radical chain resides in the bisectional 40 location that has the largest distance from the C-1 C-2 bond (hereafter exo-bisectional). Both models favor an attack of the O-radical onto the Si face of C-4 thus leading to allo-muscarine precursor 8b as major bromocyclization product.…”