Direct Synthesis of Polyfunctionalized Unsaturated δ-Lactones and δ-Lactams from α-Alkenoyl α-Carboxyl/Carbamoyl Ketene S,S-Acetals under Vilsmeier Conditions

Abstract

An efficient method for direct synthesis of polyfunctionalized unsaturated delta-lactones 2 and delta-lactams 4 has been developed from the reaction of the easily available alpha-alkenoyl alpha-carboxyl/carbamoyl ketene S,S-acetals 1/3 and Vilsmeier reagents (DMF/POCl(3) or DMF/PBr(3)) via a cyclization followed by a halovinylation or haloformylation sequence.

Transition-metal mediated carbon–sulfur bond activation and transformations

“…[72][73][74] Organoindium compounds were reported to couple with thioesters. In the presence of Pd(MeCN) 2 Cl 2 as catalyst, the reaction of thioesters (111) with aryl, primary and secondary alkyl organoindium reagents underwent to give aryl-alkyl ketones 112 in 55-95% yields (eqn (43)). 86 This method has two advantages over the crosscoupling of thioesters with organo-boron and -tin reagents: (a) no added copper(I) reagent was required to mediate the reaction, and (b) for the case of alkyl transfer, no added base was required to activate the organoindium reagents for the crosscoupling as is usually required for the coupling of alkylboron reagents with thioesters.…”

“…Dithioacetal functionalities are very useful protecting, stabilizing and promoting groups in organic synthesis, due to their easy deprotection to the corresponding aldehydes and ketones under acidic conditions. [96][97][98][99][100][101][102][103][104][105][106][107][108][109][110][111][112][113][114] Because a strong bond can be easily formed between a catalytic metal and the sulfur atom, it is usually difficult to render the metal-involved reactions of dithioacetals catalytic. In addition, dithioacetals are sensitive to acids, the organic transformations of dithioacetals via C-S bond cleavage are usually carried out by means of strong base catalysts as well as Brønsted acids.…”

Polarity-Reversible Conjugate Addition Tuned by Remote Electronic Effects

“…However, in one case where the enone moiety of N -aryl-cinnamoylacetamide 1 has a β-electron-rich 4-methoxyphenyl group, the intramolecular aza-Michael adduct 2b was produced in 20% yield (Scheme ) . The significant difference in the orientation of the conjugate addition reactions, which has not been defined in the literature, ,,− prompted us to initiate studies on the structural dependence of the cyclization process. In this communication we describe a new concept, polarity-reversible conjugate addition, based on the fact that the polarity of a classical Michael acceptor can be reversed and either intramolecular aza-Michael-adducts 2 (six-membered nitrogen rings) or intramolecular aza-anti-Michael adducts 4 (five-membered nitrogen rings) can be constructed, preferentially, through remote electronic effects.…”

Recent developments of ketene dithioacetal chemistry

“…Under identical conditions, 4-chloro-5-formyl unsaturated d-lactams 156 were produced via a sequential cyclization and haloformylation of a-alkenoyl-aamido cyclic ketene dithioacetals 153 (Scheme 46). 91 A comparison of the reactivity between 154 and 155 showed that unsaturated d-lactams 155 would be more reactive toward Vilsmeier reagents than unsaturated d-lactones 154 since 155 could not be obtained under identical reaction conditions, indicating that 155 undergo further formylation easily under Vilsmeier conditions. 91 A facile synthetic route to pyrido[2,3-d]pyrimidines was developed starting from a-amido acyclic ketene dithioacetals 157 through a double [ 92 A possible mechanism for the formation of pyrido[2,3-d]pyrimidines 160 was proposed and a tandem process of 158 with excessive amounts of Vilsemeier reagent was described (Scheme 48).…”

“…91 A comparison of the reactivity between 154 and 155 showed that unsaturated d-lactams 155 would be more reactive toward Vilsmeier reagents than unsaturated d-lactones 154 since 155 could not be obtained under identical reaction conditions, indicating that 155 undergo further formylation easily under Vilsmeier conditions. 91 A facile synthetic route to pyrido[2,3-d]pyrimidines was developed starting from a-amido acyclic ketene dithioacetals 157 through a double [ 92 A possible mechanism for the formation of pyrido[2,3-d]pyrimidines 160 was proposed and a tandem process of 158 with excessive amounts of Vilsemeier reagent was described (Scheme 48). 92 In addition to the reactions of ketene dithioacetals under Vilsemeier conditions and related transformations as mentioned above, a synthetic strategy for polyfunctionalized bicyclo-[3.3.1]nonanes 169 (61-71% yields) based on a tandem three-component reaction of a-cinnamoyl ketene dithioacetals (167) 47 with oxalyl chloride was developed by Zhao and co-workers.…”