Synthesis of Dihydrothiophenes by an Amino-Directed Thioisomünchnone−Alkene Cycloaddition Reaction

Abstract

Dihydrothiophenes can easily be obtained by a general protocol involving the reaction of 2‐aminothioisomünchnones with electron‐deficient alkenes. The overall process can be interpreted as a sequential [3+2] cycloaddition/ring‐opening cyclization reaction. The structures of the products could be unequivocally assigned by X‐ray diffraction analysis. A theoretical study at a semiempirical level (PM3) with a further single‐point refinement of energies at the B3LYP/6−31G* level also offers mechanistic insights into the stereochemical outcome.

(3+2) Cycloadditions of Thiouronium Ylides: A Room-Temperature, One-Pot Approach to Dihydrothiophenes

“…Examples include desulfurization with Raney nickel to generate acyclic compounds and, in the case of 2-amino-4,5-dihydrothiophenes, further condensation reactions to afford dihydrothiophene-fused nitrogen heterocycles. , A number of syntheses of 4,5-dihydrothiophenes have been developed, mostly relying on classical condensation chemistry. , Such routes often require high temperatures, and/or reagents that limit functional group compatibility. The application of [3+2] cycloadditions to the synthesis of dihydrothiophenes has hitherto restricted to the use of isothiomünchnones as 1,3-dipoles …”

(3+2) Cycloadditions of Thiouronium Ylides: A Room-Temperature, One-Pot Approach to Dihydrothiophenes

“…Examples include desulfurization with Raney nickel to generate acyclic compounds and, in the case of 2-amino-4,5-dihydrothiophenes, further condensation reactions to afford dihydrothiophene-fused nitrogen heterocycles. , A number of syntheses of 4,5-dihydrothiophenes have been developed, mostly relying on classical condensation chemistry. , Such routes often require high temperatures, and/or reagents that limit functional group compatibility. The application of [3+2] cycloadditions to the synthesis of dihydrothiophenes has hitherto restricted to the use of isothiomünchnones as 1,3-dipoles …”

Synthetic Routes to Chiral Nonracemic and Racemic Dihydro- And Tetrahydrothiophenes

“…Model studies indicated that mesoionic compound 23 could react with several electrophilic alkenes, such as trans -β-nitrostyrene, − acrylonitrile, and methyl vinyl ketone, to provide transient cycloadducts progenitors of dihydrothiophene compounds. The asymmetric version of this methodology was achieved by reaction of 23 with chiral nitroalkenes − and 1,2-diaza-1,3-butadienes − derived from carbohydrates.…”

Stepwise Cycloadditions of Mesoionic Systems: Thionation of Thioisomünchnones by Isothiocyanates

“…Compound 1a (Ar 1 = Ph) was chosen as the parent thioisomünchnone; this is a stable, inherently chiral mesoionic structure that can be easily generated from a carbohydrate precursor . Moreover, previous studies have proven the versatility of this substance toward diverse dipolarophiles en route to other polycyclic systems derived from α-pyridones, chiral thiiranes, 1,2,4-triazines, and 4-oxopyrimidinium-6-olates (e.g., 4 ) …”

(3+2) Cycloadditions of Thiouronium Ylides: A Room-Temperature, One-Pot Approach to Dihydrothiophenes

“…Examples include desulfurization with Raney nickel to generate acyclic compounds and, in the case of 2-amino-4,5-dihydrothiophenes, further condensation reactions to afford dihydrothiophene-fused nitrogen heterocycles. , A number of syntheses of 4,5-dihydrothiophenes have been developed, mostly relying on classical condensation chemistry. , Such routes often require high temperatures, and/or reagents that limit functional group compatibility. The application of [3+2] cycloadditions to the synthesis of dihydrothiophenes has hitherto restricted to the use of isothiomünchnones as 1,3-dipoles …”

Synthetic Routes to Chiral Nonracemic and Racemic Dihydro- And Tetrahydrothiophenes

“…Model studies indicated that mesoionic compound 23 could react with several electrophilic alkenes, such as trans -β-nitrostyrene, − acrylonitrile, and methyl vinyl ketone, to provide transient cycloadducts progenitors of dihydrothiophene compounds. The asymmetric version of this methodology was achieved by reaction of 23 with chiral nitroalkenes − and 1,2-diaza-1,3-butadienes − derived from carbohydrates.…”

Stepwise Cycloadditions of Mesoionic Systems: Thionation of Thioisomünchnones by Isothiocyanates

“…Compound 1a (Ar 1 = Ph) was chosen as the parent thioisomünchnone; this is a stable, inherently chiral mesoionic structure that can be easily generated from a carbohydrate precursor . Moreover, previous studies have proven the versatility of this substance toward diverse dipolarophiles en route to other polycyclic systems derived from α-pyridones, chiral thiiranes, 1,2,4-triazines, and 4-oxopyrimidinium-6-olates (e.g., 4 ) …”

(3+2) Cycloadditions of Thiouronium Ylides: A Room-Temperature, One-Pot Approach to Dihydrothiophenes

“…Examples include desulfurization with Raney nickel to generate acyclic compounds and, in the case of 2-amino-4,5-dihydrothiophenes, further condensation reactions to afford dihydrothiophene-fused nitrogen heterocycles. , A number of syntheses of 4,5-dihydrothiophenes have been developed, mostly relying on classical condensation chemistry. , Such routes often require high temperatures, and/or reagents that limit functional group compatibility. The application of [3+2] cycloadditions to the synthesis of dihydrothiophenes has hitherto restricted to the use of isothiomünchnones as 1,3-dipoles …”

Synthetic Routes to Chiral Nonracemic and Racemic Dihydro- And Tetrahydrothiophenes

“…Model studies indicated that mesoionic compound 23 could react with several electrophilic alkenes, such as trans -β-nitrostyrene, − acrylonitrile, and methyl vinyl ketone, to provide transient cycloadducts progenitors of dihydrothiophene compounds. The asymmetric version of this methodology was achieved by reaction of 23 with chiral nitroalkenes − and 1,2-diaza-1,3-butadienes − derived from carbohydrates.…”

Stepwise Cycloadditions of Mesoionic Systems: Thionation of Thioisomünchnones by Isothiocyanates

“…Compound 1a (Ar 1 = Ph) was chosen as the parent thioisomünchnone; this is a stable, inherently chiral mesoionic structure that can be easily generated from a carbohydrate precursor . Moreover, previous studies have proven the versatility of this substance toward diverse dipolarophiles en route to other polycyclic systems derived from α-pyridones, chiral thiiranes, 1,2,4-triazines, and 4-oxopyrimidinium-6-olates (e.g., 4 ) …”