N-Boc-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester
[CAS# 286961-14-6]

Identification

• Classification: Chemical reagent >> Organic reagent >> Borate
• Name: N-Boc-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester
• Synonyms: 3,6-Dihydro-2H-pyridine-1-tert-butoxycarbonyl-4-boronic acid pinacol ester; N-Boc-1,2,5,6-tetrahydropyridine-4-(pinacolato)boronate
• Molecular Formula: C₁₆H₂₈BNO₄
• Molecular Weight: 309.21
• CAS Registry Number: 286961-14-6
• EC Number: 689-148-0
• SMILES: B1(OC(C(O1)(C)C)(C)C)C2=CCN(CC2)C(=O)OC(C)(C)C

Properties

• Density: 1.1±0.1 g/cm³, Calc.^*
• Melting point: 100-114 °C (Expl.)
• Index of Refraction: 1.488, Calc.^*
• Boiling Point: 348.0±52.0 °C (760 mmHg), Calc.^*
• Flash Point: 164.3±30.7 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2A	H319
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	4	H302

Discovery and Applications

N-Boc-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester is a chemical compound that plays an important role in synthetic organic chemistry, particularly in the field of medicinal chemistry and drug discovery. This compound is a boronic acid derivative, which contains both a boronic acid group and a pinacol ester, as well as a tetrahydropyridine moiety that is protected by a Boc (tert-butoxycarbonyl) group. The functional groups in this structure make it a useful reagent in a variety of reactions, including Suzuki coupling reactions, which are widely used to form carbon-carbon bonds in organic synthesis.

The discovery of N-Boc-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester can be traced to the development of new methodologies for the preparation of boronic acid derivatives with increased stability and reactivity. Boronic acids, and in particular their pinacol esters, are important intermediates in many organic transformations. The Boc protection of the amine group provides additional stability to the molecule by preventing unwanted reactions with nucleophiles and allowing for selective reactions at the boronic acid site. This protection strategy is commonly used in the synthesis of various bioactive compounds, including potential drug candidates.

N-Boc-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester has found significant applications in the synthesis of complex organic molecules, particularly in the context of the Suzuki-Miyaura coupling reaction. This reaction is one of the most important methods for forming carbon-carbon bonds and is commonly employed to synthesize biaryl compounds, which are widely used as intermediates in the pharmaceutical and agrochemical industries. By incorporating this compound into the Suzuki reaction, chemists can efficiently synthesize a variety of biaryl derivatives with potential biological activity.

The tetrahydropyridine structure is often associated with biologically active molecules, and the incorporation of a boronic acid group at the 4-position provides a versatile handle for further functionalization and derivatization. The Boc group is used in this compound to protect the amine group during the synthetic process, and it can be easily removed under mild conditions when the amine functionality is needed for subsequent reactions. The pinacol ester of the boronic acid moiety enhances the stability of the compound, allowing it to be stored and handled under standard laboratory conditions without significant decomposition.

In addition to its role in Suzuki reactions, N-Boc-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester has also been used in the development of more complex molecules, including potential drug candidates and agrochemicals. The functionalized tetrahydropyridine ring is an important scaffold in medicinal chemistry, and its incorporation into boronic acid derivatives allows for the development of compounds with diverse biological activities. The use of boronic acids in drug discovery is well-established, as they can interact with various biomolecules, including enzymes and receptors, by forming reversible covalent bonds.

This compound’s applications are not limited to the pharmaceutical and agrochemical industries. Its utility extends to the preparation of functional materials, such as organic semiconductors and polymers, where boronic acids play an important role in the formation of strong covalent bonds in materials chemistry. The versatility and stability of N-Boc-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester make it an essential building block in synthetic organic chemistry, enabling the creation of a wide range of valuable compounds.

In summary, N-Boc-1,2,5,6-tetrahydropyridine-4-boronic acid pinacol ester is a valuable reagent in organic synthesis, particularly for Suzuki coupling reactions and the preparation of biologically active molecules. The use of the Boc protection strategy and the stability provided by the pinacol ester group enhance its utility in synthetic chemistry, making it a key intermediate in the development of pharmaceuticals, agrochemicals, and functional materials. Its ability to participate in carbon-carbon bond formation reactions, combined with its compatibility in various synthetic routes, solidifies its place as an important tool in modern organic chemistry.

References

Kim, E. Y., Kang, S. T., Jung, H. et al. (2016). Discovery of substituted pyrazol-4-yl pyridazinone derivatives as novel c-Met kinase inhibitors. Archives of Pharmacal Research, 39, 453-464.
DOI: https://doi.org/10.1007/s12272-015-0703-7

Sidduri, A., Tilley, J. W. and Fotouhi, N. (2014). Functionalized Organozinc Reagents in Medicinal Chemistry: Discovery of Novel Drug Candidates. Synthesis, 46(4), 430-444.
DOI: https://doi.org/10.1055/s-0033-1338589

Verner, E. V., Vashchenko, B. V., Sosunovych, B. et al. (2023). Novel approach to saturated amino acid derivatives with isolated (hetero)cyclic rings via the hydrogenation of dienes. Chemistry of Heterocyclic Compounds, 59, 442-448.
DOI: https://doi.org/10.1007/s10593-023-03214-x