Figure 13 PTC Route to Isobenzofuranones 4. C—H ALKYLATION
Related Figures (20)
The production rate of these reactions has been increased up 138 to 700 times by the proper choice of the microreactor.”' 139 2.3. Oxygen. The solvent free autoxidation of methyl- 140 benzenes 9 to benzoic acids 10 has been obtained with high 141 conversion in the presence of CoCl,-6H,O, N-hydroxyph- 142 thalimide (NHPI), and didecyl dimethylammonium bromide 143 (DDAB) by sparging oxygen through the solution at 80 °C 144 (Scheme 4).”” 145, Scheme 5. Hydroxylation of 6-Keto Esters Photooxygenation of #-keto esters 11 through air oxidation 153 in the presence of tetraphenyl porphine (TPP) as a sensitizer 154 afforded hydroxylated compounds 12 in high yields and good 155 ee’s under LL-PTC conditions, with a cinchonine based 156 ammonium salt 13 (Scheme S).* The authors provided 157 s: evidence for the involvement of 'O, in the hydroxylation 158 reaction. 159 Scheme 7. Permanganate Promoted Asymmetric Dihydroxylation Scheme 9. PTC Route to 2-Hydroxy-3-oxoesters 2.5. Potassium Peroxomonosulfate. Potassium perox- omonosulfate KHSO,*° is an inorganic, stable, water-soluble, and environmentally safe oxidant. It is also commercially available and inexpensive; therefore, it has been used under PTC biphasic conditions for various oxidations such as the alkene epoxidation through in situ dimethyl dioxirane generation.” Aiaen vaoranti«cr craviainca nhannle DL bhava haan rantvartad 197 198 199 200 201 202 203 ars. In the case of trisubstituted enoates 23 (Z,E mixture), it was found that the best results could be obtained under acidic conditions affording 2-hydroxy-3-oxo derivatives 24 in good to excellent yields and ee’s (Scheme 9). The stereoselectivity obtained points out that both Z- and E- substrates were transformed to the same enantiomer. 191 192 193 194 s§ 195 196 229 One of the most remarkable features of PTC is the possibility 230 to perform reactions in an aqueous/organic biphasic mixture 231 without hydrolysis of sensitive organic reagents or products. In 232 fact, water phase serves as reservoir of inorganic reagents to be 233 extracted in the organic phase by the PT catalyst. However, the 234 interphase protects the hydrolysis-sensitive organic compounds 235 from hydrolysis. For example ¢€-caprolactone 31 has been 236 prepared by oxidation of cyclohexanone 30 with oxone under 237 LL-PTC (Scheme 12).** 422 Tha wascetan “hee. haaw narlacmad he hasting at 420 OC a Scheme 10. Regioselective Oxidation of Phenols to 1,2- Quinones 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 amounts of hypervalent iodine(V) compounds and dipolar aprotic solvents such as DMF. Therefore, this PTC procedure represents a more practical and efficient method to generate these useful intermediates for the synthesis of biologically important compounds. The regioselectivity observed has been tentatively ascribed (Scheme 10) to the formation of a iodine(V)—phenol complex 27 from 2-iodoxy benzenesulfonic acid (IBS), formed in situ by oxidation of proIBS with Bu,N*HSO,.. After oxygen transfer and o-quinone 26 formation, the catalytic cycle can proceed by successive oxidations by Bu,N*HSO, . It is worth noting that the same reaction afforded mainly p-quinones when carried out in aqueous acetonitrile. The oxidation of benzylic methylene compounds 28 to ketones 29 was realized with good-to- excellent yields through a 1 #4 aaX% 22 4 =~ £,f-Disubstituted enones proved to be quite recalcitrant 257 substrates toward epoxidation. In particular, /,f-disubstituted 258 enones 37 bearing a trifluoromethyl group could not be 259 converted to the corresponding epoxides 39 until the 260 asymmetric aerobic oxidation, induced by H,N-NHMe and 261 catalyzed by the cinchonidinium salt 38, was recently 262 discovered (Scheme 15).*° The authors proposed that this 263 s1 epoxidation proceeds through the in situ generation of highly 204 reactive and pure H,O). In fact, when 50% H,O, was used 26s instead of the air/base/methylhydrazine system, the same 266 stereoselectivity was observed, although in a lower 66% yield. 267 A new type of bis-quaternary cinchonidine based ammonium 253 bromides 35 has been used for the oxidation of a variety of 254 chalcones 34 to the corresponding epoxides 36 with excellent 255 yield and enantioselectivity (Scheme 14).°” 256 s! Scheme 16. Asymmetric Enone Epoxidation Scheme 15. Aerobic Epoxidation of £-Trifluoromethyl-f,f- disubstituted Enones 270 quinidine-derived ammonium salt 40 (Scheme 16).°? Also this 271 simplified protocol, that does not use an hazardous compound formations toward the synthesis of various chiral compounds bearing a quaternary carbon center. More versatile a,a- dialkylmalonates 63 have been obtained through double PTC alkylation of 4-bromo benzylideneamino tert-butyl a-methyl- malonate (61) since the intermediate 4-bromobenzyloxime ester 62 could be selectively hydrolyzed by IN NaOH (Scheme 21). 399 results have been obtained with a tailored bifunctional catalyst 400 bearing a Bronsted acid site capable to activate the isonitrile, 401 thus favoring a preorganized transition state along with the 402 chiral cation.°” Scheme 23. Ring Opening of Aziridines Scheme 22. Use of Co(III) Complexes as PT Catalysts The enantioselective nucleophilic aromatic arylation (SyAr) 403 of f-keto ester $5c with activated aromatic fluorides has been 404 realized under PTC conditions with the benzoylated 40s cinchonidinium salt 75 (Scheme 25).°° 406 82 Moreover, the SyAr of 3-aryloxindoles 76 on aryl fluorides 407 with the binaphthyl bifunctional quaternary phosphonium 40s bromide 77 (Scheme 26) as PT catalyst, afforded triaryl- 409 s26 methanes 78 with good to high enantioselectivities.“* 410 Scheme 24. Enantioselective Synthesis of Indolines Scheme 25. SyAr Arylation of #-Keto Esters Scheme 28. Alkylation of 5H-Oxazol-4-ones Scheme 29. Stereoselective Base-Free PTC Reactions that some reactive substrates may react under aqueous—organic 49 biphasic systems without the need of any added base. 49) Scheme 30. PTC Reaction under Dilute Aqueous Conditions
