(1R,2R)-N-Tert.-butoxycarbonylcyclohexane-1,2-diamine

• CAS: 146504-07-6
• Catalog Number: ACM146504076
• Category: Main Products
• Molecular Weight: 214.30
• Molecular Formula: C₁₁H₂₂N₂O₂
• Synonyms: trans-2-morpholinocyclohexanol
• IUPAC Name: tert-butylN-[(1R,2R)-2-aminocyclohexyl]carbamate
• Canonical SMILES: CC(C)(C)OC(=O)NC1CCCCC1N
• InChI Key: AKVIZYGPJIWKOS-RKDXNWHRSA-N
• Boiling Point: 322.1ºC at 760 mmHg
• Flash Point: 148.6ºC
• Density: 1.02 g/cm³
• Exact Mass: 214.16800
• Hazard Statements: C: Corrosive
• Safety Description: S26

Case Study

(1R,2R)-trans-N-Boc-1,2-cyclohexanediamine for Asymmetric Catalysis of Prochiral Cyclohexanone Derivatives

Gammack Yamagata, Adam D., et al. Angewandte Chemie International Edition, 2015, 54(16), 4899-4903.

A novel catalytic asymmetric desymmetrization reaction has been established for producing enantioenriched derivatives of 2-azabicyclo[3.3.1]nonane, an important structural feature found in various alkaloids. Utilizing a primary amine organocatalyst derived from cyclohexanediamine, a diverse array of prochiral cyclohexanone derivatives with an α,β-unsaturated ester group at the 4-position were transformed into bicyclic products. These products contain three stereogenic centers and were obtained as single diastereoisomers with high enantioselectivity (83-99 % ee) and in good yields (60-90 %).
A series of commonly used chiral monoenantiomer primary 9 and secondary 10 amine organocatalysts 4a - 4e were screened for the model system at 20 mol % loading in the presence of benzoic acid as a cocatalyst. (1R,2R)-cyclohexanediamine (4e) was the most promising lead compound in terms of reactivity and enantioselectivity, and derivatives were further sought to improve enantioselectivity. Among them, the commercially available (1R,2R)-trans-N-Boc-1,2-cyclohexanediamine (4j) gave similar results to 4e, with a yield of up to 87%, a diastereomeric ratio (d.r.) >98:2, and an ee value of 64%.

(1R,2R)-Trans-N-Boc-1,2-Cyclohexanediamine for The Synthesis of Dimeric Cu(Ⅱ) Catalysts

Jack Devonport, et al. JACS Au, In press, 2021, hal-03375148.

A dimeric Cu(Ⅱ) complex catalyst [Cu(ll)2L2(μ2-Cl)Cl] (1) consisting of an asymmetric tridentate (NNO) ligand and a weakly coordinating anion was synthesized using (1R,2R)-trans-N-Boc-1,2-cyclohexanediamine as a starting material. The catalyst can initiate the C-H bond activation process of alkynes. This unusual C-H activation method is suitable for the efficient synthesis of propargylamines without the need for additives.
Synthesis of dimeric Cu(Ⅱ) complex catalyst
· trans-2-Aminocyclohexyl(imino)methyl)-4,6-di-tert-butylphenol hydrochloride, referred to as HL.HCl, was prepared through a two-step process using commercially available racemic trans-N-Boc-1,2-cyclohexanediamine. The initial step involved the condensation of this compound with 3,5-di-tert-butylsalicylaldehyde, resulting in the formation of the Boc-protected Schiff base, HL-Boc. This intermediate was subsequently deprotected with hydrochloric acid to yield HL as its hydrochloride salt with a quantitative yield. Due to the susceptibility of the HL.HCl ligand to hydrolysis into the corresponding amine and aldehyde, as indicated by 1H-NMR analysis, it was utilized directly in the synthesis of the copper catalyst, 1, without undergoing further purification.
· Considering the monoprotic nature of the ligand, this work opted for the weakly binding chloride anion to inhibit the formation of the CuL2 species. The reaction involving HL.HCl, CuCl2, and Et3N in methanol, maintained at a molar ratio of 1:1:3, resulted in the synthesis of compound 1 with a yield of 43%. This air-stable green crystalline material can be produced on a gram scale.

Synthetic Use

Upstream Synthesis Route 1

• 24424-99-5
• 20439-47-8

• 146504-07-6

Reference: [1] Journal of the Chemical Society, Dalton Transactions, 2001, # 14, p. 2188 - 2198

Upstream Synthesis Route 2

• 315179-47-6

• 146504-07-6

Reference: [1] Journal of Organic Chemistry, 2000, vol. 65, # 23, p. 7807 - 7813

Upstream Synthesis Route 3

• 24424-99-5
• 20439-47-8

• 146504-07-6

Reference: [1] Synlett, 2017, vol. 28, # 11, p. 1278 - 1281

Upstream Synthesis Route 4

• 24424-99-5
• 20439-47-8

• 146504-07-6

Reference: [1]Uppadine; Keene; Beer
[Journal of the Chemical Society, Dalton Transactions, 2001, # 14, p. 2188 - 2198]

Downstream Synthesis Route 1

• 17261-28-8
• 146504-07-6

• 315179-52-3

Reference: [1]Pálvölgyi, Ádám Márk; Schnürch, Michael; Bica-Schröder, Katharina
[Tetrahedron, 2020, vol. 76, # 51]
[2]Liu, Weigang; Pan, Hongjie; Tian, Hua; Shi, Yian
[Organic Letters, 2015, vol. 17, # 16, p. 3956 - 3959]
[3]Current Patent Assignee: Institute of Chemistry (in: CAS); CHINESE ACADEMY OF SCIENCES - CN105017172, 2017, B
Location in patent: Paragraph 0042; 0043; 0045
[4]Kim, Young Kook; Lee, Seok Jong; Ahn, Kyo Han
[Journal of Organic Chemistry, 2000, vol. 65, # 23, p. 7807 - 7813]

Downstream Synthesis Route 2

• 146504-07-6
• 5659-93-8

• 323187-46-8

Reference: [1]Marson; Schwarz
[Tetrahedron Letters, 2000, vol. 41, # 46, p. 8999 - 9003]
[2]Reiersølmoen, Ann Christin; Solvi, Thomas N.; Fiksdahl, Anne
[Beilstein Journal of Organic Chemistry, 2021, vol. 17, p. 186 - 190]

* For details of the synthesis route, please refer to the original source to ensure accuracy.