Redox-Neutral α-C–H Bond Functionalization of Secondary Amines with Concurrent C–P Bond Formation/N-Alkylation

Abstract

Redox-neutral formation of C–P bonds in the α-position of amines was achieved via a process that features a combination of an oxidative α-C–H bond functionalization and a reductive N-alkylation. Benzoic acid functions as an efficient catalyst in this three-component reaction of cyclic secondary amines, aldehydes and phosphine oxides to provide rapid access to α-amino phosphine oxides not easily accessible by classic Kabachnik-Fields reactions.

The Azomethine Ylide Route to Amine C–H Functionalization: Redox-Versions of Classic Reactions and a Pathway to New Transformations

“…We subsequently developed a redox variant of the Kabachnik–Fields reaction (Scheme 8 ). 35 This transformation is best conducted as a three-component process. The optimized conditions differ slightly from those developed for the redox-Strecker reaction in that 2-EHA acid is replaced with benzoic acid.…”

A Straightforward Synthesis of Six‐Membered‐Ring Heterocyclic α‐Aminophosphonic Acids from N‐Acyliminium Ions

“…Additionally, these cyclic amino acids have also been used as precursors for the preparation of more complex scaffolds exhibiting pharmacological activities or acting as organocatalysts . The preparation of their phosphonic analogues 5 – 8 has not been explored sufficiently with scarce reports being published so far , despite the acknowledgement of the importance of α‐aminophosphonic acids and their derivatives in organic and medicinal chemistry . Hence, there is still strong need to develop new procedures for the preparation of this class of compounds .…”

Redox‐Neutral C1 Functionalization of Unprotected Tetrahydroisoquinolines with Diazo Carbonyl Compounds

“…In the past years, the redox-neutral a-CÀHb ond functionalizations of secondary amines involving exo/endo-iminiumi somerization have been reportedb yS eidel and other research groups. [8][9][10][11][12][13][14][15] The transition of exo-iminium ion 4 into endo-iminiumi on 6 is proposed to be accomplished by iminium deprotonation/reprotonation via an azomethine ylide intermediate. Carboxylica cids [11][12][13][14][15] and transition-metals such as Cu, [9a-c] Ag, [9e, 12a] and Au, [9d] have been developedt op romote this process.…”

“…[8][9][10][11][12][13][14][15] The transition of exo-iminium ion 4 into endo-iminiumi on 6 is proposed to be accomplished by iminium deprotonation/reprotonation via an azomethine ylide intermediate. Carboxylica cids [11][12][13][14][15] and transition-metals such as Cu, [9a-c] Ag, [9e, 12a] and Au, [9d] have been developedt op romote this process. Another efficient method to suppress the formation of exo-functionalizedp roducts is to increaset he steric hindrance of benzaldehyde,a sd emonstrated by Seidel in the Cu-catalyzed redox-neutral a-alkynylation of secondary amines.…”

“…Another efficient method to suppress the formation of exo-functionalizedp roducts is to increaset he steric hindrance of benzaldehyde,a sd emonstrated by Seidel in the Cu-catalyzed redox-neutral a-alkynylation of secondary amines. [9a] Althoughavariety of redox-neutral CÀ Hf unctionalizations,i ncluding alkynylation, [9] arylation, [10] alkylation, [11] phosphonylation, [12] amination, [13] oxygenation, [14] and sulfenylation [15] have been developed, the introductiono f ad iazo unit to the a-positiono fs econdary amines via redox-neutralC ÀHf unctionalization has not been reporteds of ar. [16] With these considerations in mind, we started to test the feasibility of proposed three-component reactionb yu sing un-protectedT HIQ 1,2 ,6-dimethylbenzaldehyde 2,a nd ethyl diazoacetate 3 (EDA) as the substrates.…”