Free Amino Group Transfer via α‐Amination of Native Carbonyls

Abstract

We report herein a straightforward transfer of a free amino group (NH 2 ) from a commercially available nitrogen source to unfunctionalized, native carbonyls (amides and ketones) resulting in direct α-amination. Primary α-amino carbonyls are readily produced under mild conditions, further enabling diverse in situ functionalization reactions-including peptide coupling and Pictet-Spengler cyclization-that capitalize on the presence of the unprotected primary amine.

Enantioselective Formation of α-Amino Acid Derivatives via [2,3]-Sigmatropic Rearrangement of N-Acyl Iminosulfinamides

“…In summary, we have developed [2,3]-sigmatropic rearrangement of N -acyl iminosulfinamides with excellent 1,4-chirality transfer. The nitrogen analogue of the aza-Mislow–Evans rearrangement allows construction of α-amino secondary amides with high enantiopurity, which complements the previously reported nitrogen analogue of oxy-Mislow–Evans rearrangement that provides asymmetric access to α-amino tertiary amides . Our rearrangement currently requires multistep preparation of enantioenriched primary N - tert -butyliminosulfinamide 5 (Scheme ).…”

“…Enantioselective introduction of an amino group at the α-position of carboxylic acid derivatives is one of the most important transformations to access chiral α-amino acid derivatives and is achieved mainly through asymmetric α-amination involving polar or radical intermediates. In contrast, we are aware of only two approaches based on [2,3]-sigmatropic rearrangement. , In the first approach, chemoselective electrophilic amide activation is followed by attack from the oxygen atom of sulfinamides to produce amino-vinyloxy-sulfonium intermediates that undergo [2,3]-sigmatropic rearrangement and subsequent cleavage of the S–N bond (Scheme a) . This process can aminate α-alkyl-substituted tertiary amides with high enantioselectivity, but whether it works well with α-aryl-substituted amides is unclear.…”

Synthesis of α-heterofunctionalized carbonyl compounds via Brønsted acid-catalyzed oxygenative coupling of ynamides

“…6 c The second approach involves electrophilic amide activation by Tf 2 O/2-I-pyr, followed by oxidation with 2,6-lutidine- N -oxide (Scheme 1C). 7 The resulting enolonium equivalent B undergoes cyclization into the epoxide C , capable of alkylating a diverse range of nucleophiles, including alcohols and thiols. However, the amide activation protocol requires tertiary amides derived from basic amines, and the product amides cannot be readily transformed through acyl transfer.…”

Acid-Catalyzed Highly Enantioselective Synthesis of α-Amino Acid Derivatives from Sulfinamides and Alkynes

“…However, the substrate scope and enantioselectivity were unsatisfactory. In a complementary approach by the same group, treatment of chiral sulfinamides with similar reaction intermediates generated in situ from amide activation yielded the UAA derivatives with an inverted configuration and improved enantioselectivity . An intramolecular rearrangement reaction of chiral iminosulfinamides recently also resulted in similar products …”

“…A proposed catalytic cycle is depicted in Figure . − , The ynamide reacted with HNTf 2 to form a keteniminium species, which was subsequently captured by sulfinamide through O -addition. The kinetically favored ( E )-enolonium intermediate underwent rapid [2,3]-rearrangement to give an α-amino acid skeleton, thereby releasing a proton as catalyst for further catalytic cycle.…”