Tetrahydro-1,3-oxazepines via Intramolecular Amination of Cyclopropylmethyl Cation

Abstract

An efficient synthesis of tetrahydro-1,3-oxazepines was developed involving the regioselective intramolecular amination of cyclopropylmethyl cation. The cation was generated by the abstraction of one imidate group in bis-imidate bearing a carbocation-stabilizing substituent. Using 1,1,2,3-tetrasubstituted cyclopropane substrates, highly diastereoselective intramolecular amination to trans-tetrahydro-1,3-oxazepines was achieved. The resulting tetrahydro-1,3-oxazepines were transformed to the homoallylamine derivatives in high yields.

Synthesis of two 2,3,4,5‐tetrahydrooxepin‐7‐ylamino)benzoate derivatives as antibacterial agents against Escherichia coli and Staphylococcus aureus

“…In the literature there are several protocols for synthesis of different oxepine analogs; however, these methods these techniques involve expensive reagents which are difficult to handle. [5][6][7][8][9][10][11][12] The objective of this investigation was to prepare two oxepine-analogs using some chemical tools as follows:…”

“…[10] In addition, a report display the preparation of an oxazepine analog via intramolecular amination of cyclopropylmethyl cation. [11] Recently, an oxazepine-steroid analog was synthesized from a steroid derivative, 4-Nitro-phenyl-acetonitrile and 5-hexyn-1-ol. [12] These data show the synthesis of some oxazepine-analogs using different methods; nevertheless, some of these techniques involve expensive reagents which are difficult to handle.…”

Annulative Allylic Alkylation Reactions between Dual Electrophiles and Dual Nucleophiles: Applications in Complex Molecule Synthesis

“…[14] While this transformation at first seems trivial, it is worth nothingt hat the analogous Knoevenagel condensation between cinnamaldehyde and dimethyl malonate is much lower-yielding due to an unfavorable equilibrium betweent he product and startingm aterials (Scheme 5b). [15] Additionally,i n the presence of ab identate nucleophile such as tetraester 13, acylal 11 is converted to ac yclopropane (14;S cheme 5a)-a transformation that would be difficult to envision startingf rom cinnamaldehyde directly. [14] Barry M. Trost In their effortst od evelop as hort synthesis of 4,6-O-protected glycals, Holzapfela nd van Heerden also found allylic alkylation of a gem-diacetate to be preferable to condensation with the corresponding aldehyde.…”

“…Trost was the first to report the double substitution of an allylic gem ‐diacetate, when he demonstrated that cinnamaldehyde‐derived acylal 11 condensed with dimethyl malonate in the presence of catalytic palladium to generate diene 12 (Scheme a) . While this transformation at first seems trivial, it is worth nothing that the analogous Knoevenagel condensation between cinnamaldehyde and dimethyl malonate is much lower‐yielding due to an unfavorable equilibrium between the product and starting materials (Scheme b) . Additionally, in the presence of a bidentate nucleophile such as tetraester 13 , acylal 11 is converted to a cyclopropane ( 14 ; Scheme a)—a transformation that would be difficult to envision starting from cinnamaldehyde directly …”

Brookhart's Acid‐Catalyzed Switchable RegioselectiveN‐Alkylation of Arylamines/Heterocyclic Amines with Cyclopropylcarbinols by Temperature Regulation

“…The substituents attached to cyclopropylcarbinol play a significant role in determining which route will be favoured, given their direct effect on the stabilization/destabilization of the resultant carbocation. Very few procedures have been established [10][11][12][13] for amination of cyclopropylcarbinyl carbocation due to a limited array of amine nucleophiles compatible with acidic conditions employed to initiate the reaction.…”