Stereoselective Synthesis of Tri- and Tetrasubstituted Olefins via 1,6-Additions of Diazo Compounds and Their Precursors to p-Quinone Methides

Abstract

Reactions of para-quinone methides (p-QMs) with α-diazo-β-ketosulfones and their corresponding esters as well as simple β-dicarbonyl compounds and β-ketosulfones have been carried out under basic conditions. While the reaction of diazosulfone with p-QMs afforded trisubstituted olefins via deacylative 1,6-addition and elimination, α-diazo-β-ketoesters and various active methylene compounds such as 1,3-dicarbonyls and β-ketosulfones afforded tetrasubstituted olefins via 1,6-addition and aerial oxidation. These simple, environmentally benign, and mechanistically diverse protocols provided the products in moderate to excellent yields and selectivities.

Figure 1

Importance of tri- and tetrasubstituted olefins.

Scheme 1. Reactivity of Diazoesters, Diazophosphonates, and Diazosulfones with p-QMs

Scheme 2. Scope of p-QM in the Synthesis of Trisubstituted Olefins^,,,

Reaction scale: p-QM 1 (0.2 mmol), diazosulfone 2 (0.3 mmol, 1.5 equiv), and NaOH (0.8 mmol, 4 equiv) in EtOH (3 mL). Isolated yields after silica gel column chromatography. Z/E ratio was determined by ¹H NMR. In all of the cases, 5–10% of the ethoxide addition product was observed as a side product.

Scheme 3. Plausible Mechanism for the Formation of Trisubstituted Olefins from Diazosulfone and p-QM

Scheme 4. KOH-Mediated Reaction of p-QM with Diazoester in EtOH

Scheme 5. Scope of p-QM in the Synthesis of Tetrasubstituted Olefins Using Diazoester (Method A)^,,

Reaction scale: p-QM 1 (0.2 mmol), diazoketoester 6 (0.24 mmol, 1.2 equiv), and KOH (0.8 mmol, 4 equiv) in CH₃CN (3 mL). Isolated yields after silica gel column chromatography, 5–10% of di-tert-butylquinone was isolated in all of the cases (see Scheme 8). E/Z ratio was determined by ¹H NMR. After recrystallization of 75:25 mixture from chloroform.

Scheme 6. Plausible Mechanism for the Formation of Tetrasubstituted Olefins from Diazoester and p-QM

Scheme 7. Scope of p-QM in the Synthesis of Tetrasubstituted Olefins Using Active Methylene Compounds (Method B)^,,

Reaction scale: 0.3 mmol each of p-QM 1 and active methylene compound 9 and 1.2 mmol of KOH. Isolated yields after silica gel column chromatography. E/Z ratio was determined by ¹H NMR. After recrystallization of original the 80:20 mixtures from ethyl alcohol/petroleum ether (20:80).

Scheme 8. Control Experiments

Scheme 9. Plausible Mechanism for the Formation of Tetrasubstituted Olefins from Active Methylene Compounds and p-QM

Scheme 10. Reaction of Diazosulfone, Diazoester, and a 1,3-Dicarbonyl with N-Methyl Isatin Derived p-QM