Ambident Reactivity of Nitroso Compounds for Direct Amination and Hydroxylation of Carbonyls

Abstract

Functionalization of carbonyls, particularly with a heteroatom subunit, is an important synthetic transformation. Utilization of ambident electrophiles for such a strategy is advantageous because two different heteroatom units can be installed from a single source under judicial reaction conditions. Recently, there have been increased examples for the construction of C–O and C–N bonds using nitroso compounds, a prototype of ambident electrophiles. In this short review, we discuss the advantages and challenges of exploiting nitroso compounds in organic synthesis with specific focus on nitroso aldol type processes for the direct hydroxylation and amination of carbonyl compounds.1 Introduction2 Prime Challenges in Nitroso Aldol Reactions3 Direct Hydroxylation Reactions4 Direct Amination Reactions5 Conclusion and Outlook

Direct N–O bond formation via oxidation of amines with benzoyl peroxide

“…Meanwhile, it is well known that hydroxyl amine is the best source of reactive nitroso (N–O bond) intermediates8 and for a decade we have used these intermediates to synthesize various new types of N-selective (C–N–O) as well as O-selective (C–O–N) bond-containing synthetically useful chiral compounds as well as bioactive compounds 9. We are eager to investigate if N–O bond formation could be achieved by choosing suitable reaction conditions using amines and benzoyl peroxide.…”

Generating Skeletal Diversity and Complexity from Boron‐Substituted 1,3‐Dienes and Enophiles

“…For example, we previously reported the reactivity of these versatile building blocks as dienes towards aryl nitroso compounds and showed that they are valuable precursors of important heterocycles such as pyrroles, furans, nitrones and oxazines (Scheme ) . The polarization of the nitrogen–oxygen bond of nitroso derivatives confers them high reactivity . For this reason, besides [4+2] cycloadditions, they can also be involved in a large number of other processes, whether metal‐catalyzed or not, with enolizable carbonyl compounds,[4a], [4b], [4e], [4f], [4h], Grignard reagents, amines[4b], or can be used for scavenging radicals.…”

“…The polarization of the nitrogen–oxygen bond of nitroso derivatives confers them high reactivity . For this reason, besides [4+2] cycloadditions, they can also be involved in a large number of other processes, whether metal‐catalyzed or not, with enolizable carbonyl compounds,[4a], [4b], [4e], [4f], [4h], Grignard reagents, amines[4b], or can be used for scavenging radicals. [4b], [4f], Activated by an electron‐withdrawing group, they are also excellent partners for participating in ene reactions.…”

“…For this reason, besides [4+2] cycloadditions, they can also be involved in a large number of other processes, whether metal‐catalyzed or not, with enolizable carbonyl compounds,[4a], [4b], [4e], [4f], [4h], Grignard reagents, amines[4b], or can be used for scavenging radicals. [4b], [4f], Activated by an electron‐withdrawing group, they are also excellent partners for participating in ene reactions. [4b], [4c], [4j], Unlike nitroso arenes, acyl nitroso species have not been isolated, except in exceptional cases, and have mostly been generated in situ by oxidation of hydroxamic acid derivatives .…”

“…[4b], [4f], Activated by an electron‐withdrawing group, they are also excellent partners for participating in ene reactions. [4b], [4c], [4j], Unlike nitroso arenes, acyl nitroso species have not been isolated, except in exceptional cases, and have mostly been generated in situ by oxidation of hydroxamic acid derivatives . Through reaction with 1,3 dienes, they mainly provide the corresponding 3,6‐dihydro‐2 H ‐1,2‐oxazines via a Diels Alder [4+2]‐cycloaddition.…”