What is it about?
SnAP (Sn (tin) amine protocol) hydrazine reagents and aldehydes undergo oxidative, copper mediated coupling to form substituted 1,4,5-oxadiazepanes and 1,2,5-triazepanes. Unlike all prior reactions involving SnAP reagents, the SnAP hydrazine reagents undergo a molecular oxygen-assisted oxidative cyclization. The air- and moisture tolerant transformation accommodates a broad range of groups including electron-rich, electron-poor aromatic, heteroaromatic, and aliphatic aldehydes and is amenable to gram scale synthesis. These unusual, chiral heterocycles have unexpectedly large optical rotations, which may find use in optical materials.
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This page is a summary of: Copper Promoted Oxidative Coupling of SnAP Hydrazines and Aldehydes to Form Chiral 1,4,5-Oxadiazepanes and 1,2,5-Triazepanes, Helvetica Chimica Acta, October 2017, Wiley,
DOI: 10.1002/hlca.201700199.
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SnAP Reagents for a Cross-Coupling Approach to the One-Step Synthesis of Saturated N-Heterocycles
Sigma-Aldrich SnAP reagents highlight (also: http://www.sigmaaldrich.com/technical-documents/articles/technology-spotlights/snap-reagents.html)
2-(((Tributylstannyl)methyl)thio)- ethanamine, 2-((Tributylstannyl)-methoxy)ethanamine, and tert-Butyl (2-aminoethyl)((tributylstannyl)methyl)-carbamate
e-EROS Encyclopedia of Reagents for Organic Synthesis SnAP Reagents Highlight.
SnAP Reagents for the Transformation of Aldehydes into Substituted Thiomorpholines - An Alternative to Cross-Coupling with Saturated Heterocycles
It's a SnAP! The transformation of aldehydes into N-unsubstituted 3-thiomorpholines provides a convenient alternative to metal-catalyzed cross-coupling reactions, which are generally unsuited to the functionalization of saturated N-heterocycles. A copper-mediated radical cyclization is the key to the mild conditions, high functional group tolerance, and broad substrate scope offered by these reagents.
SnAP Reagents for the Synthesis of Piperazines and Morpholines
Substituted piperazines and morpholines are valuable structural motifs in biologically active compounds, but are not easily prepared by contemporary cross-coupling approaches. In this report, we introduce SnAP reagents for the transformation of aldehydes into N-unprotected piperazines and morpholines. This approach offers simple, mild conditions compatible with aromatic, heteroaromatic, aliphatic, and glyoxylic aldehydes and provides mono- and disubstituted N-heterocycles in a single step.
SnAP reagents for the one-step synthesis of medium-ring saturated N-heterocycles from aldehydes
Interest in saturated N-heterocycles as scaffolds for the synthesis of bioactive molecules is increasing. Reliable and predictable synthetic methods for the preparation of these compounds, especially medium-sized rings, are limited. We describe the development of SnAP (Sn amino protocol) reagents for the transformation of aldehydes into seven-, eight- and nine-membered saturated N-heterocycles. This process occurs under mild, room-temperature conditions and offers exceptional substrate scope and functional-group tolerance. Air- and moisture-stable SnAP reagents are prepared on a multigram scale from inexpensive starting materials by simple reaction sequences. These new reagents and processes allow widely available aryl, heteroaryl and aliphatic aldehydes to be converted into diverse N-heterocycles, including diazepanes, oxazepanes, diazocanes, oxazocanes and hexahydrobenzoxazonines, by a single synthetic operation.
Catalytic Synthesis of N-Unprotected Piperazines, Morpholines, and Thiomorpholines from Aldehydes and SnAP Reagents
Commercially available SnAP (stannyl amine protocol) reagents allow the transformation of aldehydes and ketones into a variety of N-unprotected heterocycles. By identifying new ligands and reaction conditions, a robust catalytic variant that expands the substrate scope to previously inaccessible heteroaromatic substrates and new substitution patterns was realized. It also establishes the basis for a catalytic enantioselective process through the use of chiral ligands.
Bespoke SnAP Reagents for the Synthesis of C‑Substituted Spirocyclic and Bicyclic Saturated N‑Heterocycles
The precise placement of C-substituents on bicyclic and spirocyclic N-heterocycles is readily achieved by the combination of aldehydes and new SnAP reagents. The substituted SnAP reagents are readily prepared from simple starting materials and couple with a variety of aromatic and heteroaromatic aldehydes at room temperature under operationally simple conditions to deliver substituted morpholine and piperazine products.
SnAP-eX Reagents for the Synthesis of Exocyclic 3‑Amino- and 3‑Alkoxypyrrolidines and Piperidines from Aldehydes
SnAP-eX (tin amine protocol, exocyclic heteroatoms) reagents allow the single-step transformation of aldehydes and ketones into 2,3-disubstituted pyrrolidines and piperidines containing exocyclic amine or alkoxy groups. These saturated N-heterocycles are of importance in modern drug discovery approaches and are prepared in moderate yields using an operationally simple protocol that is compatible with a range of functional groups and heterocyclic aldehydes.
Silicon Amine Reagents for the Photocatalytic Synthesis of Piperazines from Aldehydes and Ketones
Silicon amine protocol (SLAP) reagents for photocatalytic cross-coupling with aldehydes and ketones to form N-unprotected piperazines have been developed. This blue light promoted process tolerates a wide range of heteroaromatic, aromatic, and aliphatic aldehydes and structurally and stereochemically complex SLAP reagents. It provides a tin-free alternative to SnAP (tin amine protocol) reagents for the synthesis of substituted piperazines.
Continuous Flow Synthesis of Morpholines and Oxazepanes with Silicon Amine Protocol (SLAP) Reagents and Lewis Acid Facilitated Photoredox Catalysis
Photocatalytic coupling of aldehydes and silicon amine protocol (SLAP) reagents enables the simple, scalable synthesis of substituted morpholines, oxazepanes, thiomorpholines, and thiazepanes under continuous flow conditions. Key to the success of this process is the combination of an inexpensive organic photocatalyst (TPP) and a Lewis acid additive, which form an amine radical cation that is easily reduced to complete the catalytic cycle. Di- and trisubstituted SLAP reagents are formed in one step by an iron-catalyzed aminoetherification of olefins.
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