5‐exo versus 6‐endo Thiyl‐Radical Cyclizations in Organic Synthesis

Abstract

Since the discovery of the radical mediated thiol‐ene and thiol‐yne reactions, these reactions have been employed in an intramolecular manner for the synthesis of sulfur‐containing heterocycles. Although closely related on a mechanistic basis, the thiol‐ene and thiol‐yne cyclization can differ greatly in regioselectivity and product distribution, with the thiol‐ene process being more predictable and thus attracting greater utilization. Herein, we review intramolecular thiyl‐radical addition reactions and the factors leading to the observed regioselectivity in examples in which both the 5‐exo and 6‐endo mode of cyclization are feasible. We highlight the applications of these important reactions for organic synthesis in the recent literature.

Atmospheric Oxygen Mediated Radical Hydrothiolation of Alkenes

“…Recognizing that by incorporation of a thioester, we are introducing a thiol in protected form, we were able to transform A13 to 5‐mercaptopentanoic acid ( F1 ) by subjecting the product of the hydrothiolation reaction to an acidic workup and affording the free thiol in 92 % yield (Scheme 4 A). This thiol can then easily be converted to a δ‐thiolactone by Steglich thiolactonization, delivering a class of compound important in numerous fields [17, 18, 69–75] . In addition to this, we also attempted the hydrothiolation of an alkyne (thiol‐yne reaction) [76, 77] .…”

CsPbBr3 Perovskite Photocatalyst in Chemodivergent Functionalization of N-Methylalkanamides Using CBr4

“…A plausible mechanism for the reaction is proposed based on literature reports − and control experiments (Figure a) . The redox potentials of CBr 4 and CsPbBr 3 NCs were also helpful in understanding the reaction .…”

6‐Endo‐dig versus 5‐exo‐dig: Exploring Radical Cyclization Preference with First‐, Second‐, and Third‐row Linkers using High‐level Quantum Chemical Methods

“…For example, although pre-dicted to be unfavorable (Table 1), 5-endo-trig cyclization readily occurs in systems bearing thiyl and silyl radicals (Figure 1). [14][15][16] To the best of our knowledge, there is no thorough study available in literature that sheds light on the stereoelectronic effects of large atoms on cyclization reactions. Inclusive studies on such systems that are believed to defy the known cyclization preference can eventually become complementary to Baldwin rules.…”

“…findings and theoretical predictions of similar systems 5,15. Using Marcus equation shown below (equation 1), the intrinsic barriers (DG � o ) are calculated for thermoneutral cyclization process.…”