Aza-Oxyallyl Cation Driven 3-Amido Oxetane Rearrangement to 2-Oxazolines: Access to Oxazoline Amide Ethers

Abstract

Herein, we report a highly facile and unprecedented activation of 3-amido oxetanes to synthesize 2-oxazoline amide ethers using a transient electrophilic aza-oxyallyl cation as an activating as well as an alkylating agent under mild reaction conditions. The aza-oxyallyl cation driven intramolecular rearrangement of 3-amido oxetanes to 2-oxazolines is the hallmark of this transformation and is a new addition to the reactivity profile of aza-oxyallyl cations.

Aza‐oxyallyl Cations and Their Applications in (3+m) Cycloaddition Reactions

“…Reaction processed through base mediated generation of aza‐oxyallyl cation followed by rearrangement in oxetane to deliver final product (Scheme 42). [58] …”

“…Reaction processed through base mediated generation of azaoxyallyl cation followed by rearrangement in oxetane to deliver final product (Scheme 42). [58] Recently, Suryavanshi and group developed a method to synthesize hindered N-alkyl sulfoximines derivatives 141 via in situ generated aza-oxyallyl cation and sulfoximines 140 with Na 2 CO 3 in DCM using HFIP as a co-solvent. Product showed good tolerance of functional group.…”

Synthesis and Reactivity of Fluorinated Dithiocarboxylates to Prepare Thioamides—Effective Access to a 4-Styrenylthioamide-Cinchona Alkaloid Monomer

“…In peptide chemistry, the thioamide function is a promising isostere of the amide group leading to interesting biological activities [4][5][6]. In organic chemistry, thioamide is particularly effective for the preparation of thiazoles or thiazolines and leads to higher yields compared to oxygen analogues [7][8][9]. In asymmetric synthesis, several groups including ours have described an improvement in the efficiency of thioamide organocatalysts in terms of yield and stereoselectivity compared to the amide analogues.…”

“…Nevertheless, the aminolysis with primary or secondary amines in the presence of DMAP was not possible for these compounds. To improve the reactivity of such aliphatic dithioesters (methyl or ethyl), various activating moieties have been tested (Figure 2) [24][25][26][27][28], mention should be made of benzothiazolyl [24], sulfinyl bisthiobenzoyl [25,26], or thioglycolic acid [7,8,27]. Among these, S-thiobenzoylglycolic acid represents an interesting choice.…”