Factors affecting the selection of products from a photochemically generated singlet biradical

Abstract

The chemistries of a monoradical of the ultrafast "radical-clock" type and a structurally related singlet biradical, generated by Norrish type II photochemistry, are compared. The monoradical is found to undergo the characteristic ring-opening reaction of its class at about 10(10) s(-1) at room temperature. However, the singlet biradical shows no evidence of the analogous ring-opening reaction. The contrasting chemistry is traced not to a fundamental difference in electronic structure of the two intermediates, but rather to a steric interaction that the biradical alone would have to suffer during the ring opening. Although the magnitude of the steric hindrance is small (estimated 15-20 kJ mol(-1)), it is enough to shut down the reaction, because the biradical has other facile product-forming reactions available.

Cyclooxygenase-1-Selective Inhibitors Based on the (E)-2′-Des-methyl-sulindac Sulfide Scaffold

“…53,56 In contrast to the standard procedures, which employ “activated” zinc and expensive α-haloalkanoyl esters, we reacted the indanone precursors, 8 , with inexpensive ethyl alkanoates at low temperatures using lithium diisopropylamide in tetrahydrofuran. 57 This method generated the intermediate alcohols, 9 , after an acidic quench in a much shorter time (2 h). The quantities of side products detected by HPLC were less than with the lengthy Reformatsky reaction (overnight with Zn 0 catalyst).…”

“…Modifications were made at the carboxyl, benzylidene, and 5′-position of the indene ring (Figure ). The synthetic scheme followed the general approaches previously described for assembly of sulindac analogues with some modifications (Scheme ). , In contrast to the standard procedures, which employ “activated” zinc and expensive α-haloalkanoyl esters, we reacted the indanone precursors, 8 , with inexpensive ethyl alkanoates at low temperatures using lithium diisopropylamide in tetrahydrofuran . This method generated the intermediate alcohols, 9 , after an acidic quench in a much shorter time (2 h).…”

“…59,60 Dehydration of 9a and 9b produced a mixure of exo-and endo-olefins for both 10a and 10b (Table S1 in the Supporting Information). 50,57 Steric hindrance from the exocyclic alkyl chain of the racemic mixture 10c favored conversion to the endo-olefin as indicated by HPLC analysis and by comparison to the UV spectrum of 10d, which cannot exist in the exo-form (Table S1 in the Supporting Information). Unseparated isomeric mixtures of ethyl esters, 10a−c, were employed in the subsequent condensation step.…”

First synthesis of 2‐(2,4,4‐trimethyl‐3,4‐dihydro‐2H‐benzo[h]chromen‐2‐yl)‐1‐naphthol and 3‐(2,4,4‐trimethyl‐3,4‐dihydro‐2H‐benzo[g]chromen‐2‐yl)‐2‐naphthol from 1‐ and 2‐naphthol derivatives

“…3-(1 0 -Hydroxy-1 0 -methyl ethyl)-2-naphthol (10). Grignard reagent was prepared by dropwise addition of methyl iodide (6.2 mL, 14.2 g, 0.1 mol) in ether (10 mL) to a stirred suspension of magnesium metal (2.4 g, 0.1 mol) in ether (10 mL) containing a crystal of I 2 .…”

“…Vol 48 afforded 2-(1 0 -hydroxy-1 0 -methyl ethyl)-1-naphthol 6 [10] as colorless oil in quantitative yield. Heating 6 with maleic anhydride on water bath gave 2-(2,4,4-trimethyl-3,4-dihydro-2H-benzo[h]chromen-2-yl)-1-naphthol 1 as viscous oil, which solidified on standing.…”