(aR,3aS,4S,6S,7aR)-Hexahydro-3a,8,8-trimethyl-alpha-(2-methylpropyl)-4,6-methano-1,3,2-benzodioxaborole-2-methanamine 2,2,2-trifluoroacetate
[CAS# 179324-87-9]

Identification

• Classification: Pharmaceutical intermediate >> API intermediate
• Name: (aR,3aS,4S,6S,7aR)-Hexahydro-3a,8,8-trimethyl-alpha-(2-methylpropyl)-4,6-methano-1,3,2-benzodioxaborole-2-methanamine 2,2,2-trifluoroacetate
• Synonyms: (1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butan-1-amine;2,2,2-trifluoroacetic acid
• Molecular Formula: C₁₅H₂₈BNO₂.C₂HF₃O₂
• Molecular Weight: 379.23
• CAS Registry Number: 179324-87-9
• SMILES: B1(O[C@@H]2C[C@@H]3C[C@H]([C@@]2(O1)C)C3(C)C)[C@H](CC(C)C)N.C(=O)(C(F)(F)F)O

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H332-H335
• Safety Statements: P261-P280-P305+P351+P338

Discovery and Applications

(aR,3aS,4S,6S,7aR)-Hexahydro-3a,8,8-trimethyl-α-(2-methylpropyl)-4,6-methano-1,3,2-benzodioxaborole-2-methanamine 2,2,2-trifluoroacetate is a chiral boron-containing compound notable for its complex bicyclic structure and multifunctional groups. The molecular formula is generally represented as C₁₅H₂₄BNO₄·C₂HF₃O₂, combining the boronate core with the trifluoroacetate counterion.

This compound features a benzodioxaborole ring system, which is a bicyclic structure incorporating a boron atom coordinated with oxygen atoms forming a heterocyclic ring fused to a benzene moiety. The hexahydro descriptor indicates saturation of the ring system, with multiple chiral centers designated by the stereochemical configuration (aR,3aS,4S,6S,7aR). The molecule includes three methyl groups at positions 3a and 8, as well as an α-substituted 2-methylpropyl (isobutyl) side chain, contributing to steric bulk and lipophilicity.

The methanamine group attached to the borole ring at position 2 is protonated and forms a salt with trifluoroacetic acid, resulting in the trifluoroacetate counterion. This salt form improves the compound’s solubility and stability for practical handling.

Benzodioxaborole derivatives are widely studied in organic synthesis and medicinal chemistry, notably as intermediates or catalysts in Suzuki-Miyaura cross-coupling reactions, where boron species act as transmetallation agents facilitating carbon-carbon bond formation. The chiral nature of this compound makes it valuable in asymmetric synthesis, serving as a chiral boron source or ligand for enantioselective transformations.

The trifluoroacetate salt enhances the compound’s chemical robustness and is often preferred in synthetic procedures where solubility in polar organic solvents is necessary. The presence of fluorinated counterions can also influence crystallinity and purification properties.

Physically, this compound is generally a crystalline solid, stable under standard laboratory conditions but sensitive to moisture due to the boron-oxygen bonds, which can hydrolyze. It is soluble in polar aprotic solvents such as acetonitrile, dimethylformamide, and methanol.

Chiral benzodioxaborole compounds with defined stereochemistry like this one are employed in the synthesis of pharmaceuticals, agrochemicals, and advanced materials. Their ability to transfer chiral information in catalytic cycles is crucial in the preparation of enantiomerically pure molecules.

In summary, (aR,3aS,4S,6S,7aR)-hexahydro-3a,8,8-trimethyl-α-(2-methylpropyl)-4,6-methano-1,3,2-benzodioxaborole-2-methanamine 2,2,2-trifluoroacetate is a chiral boronate salt used in asymmetric organic synthesis. Its bicyclic boron-containing core and trifluoroacetate counterion confer unique chemical properties that facilitate its role as a reagent or catalyst in enantioselective transformations.

References

2006. Bortezomib. Pharmaceutical Substances.
URL: https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-02-0106