Organic Superbases in Annulation with Propargylic Alcohols: Straightforward Synthesis of the Functionalized Oxazolopyrrolohexahydropyrimidine and Oxazolohexahydropyrimidoazepine Scaffolds
Abstract:The popular organic superbases 1,5‐diazabicyclo[4.3.0]non‐5‐ene (DBN) and 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) underwent annulation with electron‐deficient propargylic alcohols [EWG = CN, C(O)Ph, CO2Me] to afford functionalized condensed hexahydropyrimidine systems, [1,3]oxazolo[3,2‐a]pyrrolo[2,1‐b]hexahydropyrimidines and [1,3]oxazolo[3′,2′:3,4] hexahydropyrimido[1,2‐a]azepines, in good to high yields. The reactions proceeded regioselectively and, in most cases, stereoselectively under mild conditions (wi… Show more
“…A large excess of water was required for the amidation of alkyl 4hydroxybut-2-ynoates (Scheme 22a), low amounts leading to addition/cyclization reactions (see Chapter 5, Scheme 32). [50] In 1996, Dolphin and Ma disclosed the synthesis of the amidolactame depicted in Scheme 23a from TMSOTf-promoted reaction of DBU with pheophorbide a. [51] A plausible mechanism which somewhat differs from that proposed by the authors involves activation of the β-ketoester unit with TMSOTf to mediate addition of DBU, leading to 23A (Scheme 23b).…”
Section: Estersmentioning
confidence: 99%
“…[49] Similar annulation reactions occurred from the corresponding keto-and cyano-compounds (Scheme 32a). [50,60] The products would arise via Michael-type addition intermediates 32A (Scheme 32b). As depicted in Chapter 3, Shi and co-workers reported a different addition/cyclization process from -methyl alkynoates (Scheme 18a).…”
Section: Addition To C=c and C�c Bondsmentioning
confidence: 99%
“…Indeed, DBN display properties similar to those of DBU, [8] and reports describing similar results are already available. [13,18,20,30,34,40,43,44,46,49,50,51,55,62,70,73,[75][76][77][78]…”
DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) is traditionally considered to be a non-nucleophilic base. Nevertheless, DBU possesses nucleophilic properties which mediate organic reactions and may lead to the formation of compounds containing the DBU scaffold. Participation of water to the processes affords there-component products. The review covers the reactions leading to DBU derivatives showing that the interest of this sterically hindered amidine is not limited to its basic role. Proposed mechanisms are described with, in some cases, personal comments.
“…A large excess of water was required for the amidation of alkyl 4hydroxybut-2-ynoates (Scheme 22a), low amounts leading to addition/cyclization reactions (see Chapter 5, Scheme 32). [50] In 1996, Dolphin and Ma disclosed the synthesis of the amidolactame depicted in Scheme 23a from TMSOTf-promoted reaction of DBU with pheophorbide a. [51] A plausible mechanism which somewhat differs from that proposed by the authors involves activation of the β-ketoester unit with TMSOTf to mediate addition of DBU, leading to 23A (Scheme 23b).…”
Section: Estersmentioning
confidence: 99%
“…[49] Similar annulation reactions occurred from the corresponding keto-and cyano-compounds (Scheme 32a). [50,60] The products would arise via Michael-type addition intermediates 32A (Scheme 32b). As depicted in Chapter 3, Shi and co-workers reported a different addition/cyclization process from -methyl alkynoates (Scheme 18a).…”
Section: Addition To C=c and C�c Bondsmentioning
confidence: 99%
“…Indeed, DBN display properties similar to those of DBU, [8] and reports describing similar results are already available. [13,18,20,30,34,40,43,44,46,49,50,51,55,62,70,73,[75][76][77][78]…”
DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) is traditionally considered to be a non-nucleophilic base. Nevertheless, DBU possesses nucleophilic properties which mediate organic reactions and may lead to the formation of compounds containing the DBU scaffold. Participation of water to the processes affords there-component products. The review covers the reactions leading to DBU derivatives showing that the interest of this sterically hindered amidine is not limited to its basic role. Proposed mechanisms are described with, in some cases, personal comments.
“…In this decade, R 2 N–E substrates were frequently applied in cyclization reactions. The electrophilic moiety could be ketone, or imine etc. Usually, the mechanism included a conjugate addition and an intramolecular nucleophilic addition (Scheme ).…”
“…Commercial reagents like 1,5‐diazabicyclo[4.3.0]non‐5‐ene (DBN) and 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) can be applied in the R 2 N–E strategy [Eq. (27‐1)].…”
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