Primary tert‐ and sec‐Allylamines via Palladium‐Catalyzed Hydroamination and Allylic Substitution with Hydrazine and Hydroxylamine Derivatives

Abstract

Keywords allylic substitution; homogeneous catalysis; hydroamination; palladiumThe challenge of controlling the regiochemistry of palladium-catalyzed allylic substitution by choice of ancillary ligand has a long history. Much attention has been focused on controlling regiochemistry because formation of the more substituted product could be developed into a mild route to sec-and even tert-alkylamines (Scheme 1). Åkermark and co-workers reported that attack can occur at the more substituted position of a prenyl complex, but that the reversibility of this attack ultimately leads to formation of the less substituted amine in many cases.[1] More recently, Hou and co-workers reported a ligand for palladium that causes benzylamine to add irreversibly to form secondary and tertiary N-alkyl sec-butylamines, [2] and Yudin and co-workers have shown that the attack by aziridine is irreversible and that tert-alkyl-substituted aziridines can be prepared by allylic substitution. [3,4] During studies to develop the scope of the hydroamination of dienes, [5][6][7] we found that the reactions of hydrazine and hydroxylamine derivatives occur irreversibly at the more substituted position of both prenyl and crotyl palladium intermediates. We explored this transformation further because, unlike the products from additions of aziridines, [3,4] the products from addition of hydrazine and hydroxylamine derivatives could be readily transformed into primary tert-alkylamines or sec-alkylamines. The synthesis of primary amines containing tertiary alkyl groups is challenging because many of the conventional methods, such as nucleophilic substitution and additions to imines, are difficult to conduct at tertiary electrophiles and at ketimines, [8,9] and few catalytic reactions have been developed that form tert-alkylsubstituted amines. [10,11] Herein we report our studies on the reactions of hydrazine and hydroxylamine derivatives to form allylamine products from reaction at the more hindered site of aliphatic dienes or allylic ** We are grateful to the NIH (NIGMS GM-55382) for support of this work and Johnson-Matthey for palladium.

Intermolecular Cope‐Type Hydroamination of Alkenes and Alkynes

“…The hydroamination of unactivated alkenes and alkynes is an attractive approach for the synthesis of such molecules, but it is underdeveloped and remains challenging, especially for intermolecular reactions. Most recent progress has been accomplished using transition-metal catalysis, [1,2] or strong acids with less basic nitrogen nucleophiles, [3] but often procedures are limited to specific substrate classes and functional-group compatibility is either limited or yet undefined. [4] A conceptually different approach to the functionalization of alkenes and alkynes in intramolecular reactions is the Cope-type hydroamination (also referred to as reverse-Cope cyclization).…”

3‐Rhoda‐1,2‐diazacyclopentanes: A Series of Novel Metallacycle Complexes Derived From CN Functionalization of Ethylene

“…In an attempt to further validate the proposed structures for [3-7] + , ESI(+)-tandem MS/MS was performed to gain insight from characteristic fragment losses. For example, bombardment of [5] + (m/z 651) provided several daughter ions includ-ing m/z 595 for the h 2 -azo compound and m/z 551 and 451 for the mono-and bisdeprotected rhodacycles, respectively. A signal at m/z 421 was also observed for the h 2 -ethylene fragment [1] + .…”

“…This reaction has been used to readily assemble alkyl hydrazines for example, which are relevant precursors to heterocycles. [2] In terms of metal catalysts, late transition metals: Co, [3] Rh, [4] Ir, [4a] Pt, [5] Au, [6] and Zn [7] as well as early metal systems containing Ti [8] have all been used to good effect. Notably, Carreira recently reported the use of a Co III Schiff base complex which facilitates the hydrohydrazination of olefins, dienes, and enynes using azodicarboxylates (RO 2 CN=NCO 2 R) as the N source and PhSiH 3 as the terminal reductant.…”

Tertiary Carbinamine Synthesis by Rhodium‐Catalyzed [3+2] Annulation of N‐Unsubstituted Aromatic Ketimines and Alkynes

“…This formal [3 + 2] annulation would provide a convenient and waste-free complement to current synthetic routes towards tertiary carbinamines. [4] A key step in our design is the generation of a nucleophilic transition-metal-alkenyl intermediate B that is reactive towards intramolecular ketimine addition. Analogous latetransition-metal-alkenyl and aryl nucleophiles have been successfully accessed in catalytic tandem sequences initiated by other types of elementary reactions.…”