tert-Butyl tetraisopropylphosphorodiamidite

• CAS: 137348-88-0
• Catalog Number: ACM137348880
• Category: Main Products
• Molecular Weight: 304.45
• Molecular Formula: C₁₆H₃₇N₂OP
• Synonyms: Phosphorodiamidousacid,N,N,N,N-tetrakis(1-methylethyl)-,1,1-dimethylethyl ester; [tert-butyloxy]bis(N,N-diisopropylamino)phosphane; tert-butyl N,N,N,N-tetraisopropylphosphorodiamidite; tert-butyl tetraisopropylphosphordiamidite; Phosphorodiamidousacid,tetrakis(1-methylethyl)-,1,1-dimethylethyl ester (9CI); tert-Butyl tetraisopropylphosphorodiamidite; (tert-Butoxy)bis(diisopropylamino)phosphine
• IUPAC Name: N-[[di(propan-2-yl)amino]-[(2-methylpropan-2-yl)oxy]phosphanyl]-N-propan-2-ylpropan-2-amine
• Canonical SMILES: CC(C)N(C(C)C)P(N(C(C)C)C(C)C)OC(C)(C)C
• InChI Key: PSFUFSJCFKUIIG-UHFFFAOYSA-N
• Boiling Point: 330.1ºC at 760mmHg
• Melting Point: 67-74ºC(lit.)
• Flash Point: 153.4ºC
• Appearance: Light yellow solid
• Exact Mass: 304.26400
• Hazard Statements: Xi

Case Study

Tert-Butyl Tetraisopropylphosphorodiamidite as an Excellent Ligand for Pd-Catalyzed Aminations

Roiban, Gheorghe-Doru, et al. European Journal of Organic Chemistry, 2014, 10, 2070-2076.

The tert-Butyl tetraisopropylphosphorodiamidite is an excellent ligand for the palladium-catalyzed Buchwald-Hartwig amination of aryl and heteroaryl chlorides and bromides. This amination protocol is a practical approach to the synthesis of industrially important aryl and heteroaryl amines due to its easy accessibility and air stability.
· Catalyst Preparation
A stock solution of the catalyst was prepared under an inert atmosphere. Pd(dba)2 was introduced into a dried Schlenk tube, followed by tert-butyl tetraisopropylphosphorodiamidite (tBuP(iPr)2N). After purging with argon, dry toluene was added. The mixture was homogenized and stirred under an argon atmosphere.
· Amination Reaction
The reaction was conducted in a Schlenk tube. Sodium tert-butoxide (NaOtBu) and aryl halide were added, followed by purging with argon. Dry toluene, the calculated amount of catalyst, and amine were then added. The tube was sealed, homogenized, and heated in a preheated oil bath. The reaction progress was monitored using gas chromatography (GC). Upon completion, the reaction mixture was cooled, and then quenched with diethyl ether and saturated sodium chloride solution. The organic layer was separated, washed, dried, and concentrated. The crude product was purified by column chromatography.

Tert-Butyl Tetraisopropylphosphorodiamidite for 5'-Bis-Conjugation of Oligonucleotides

Meyer, Albert, et al. The Journal of Organic Chemistry, 2010, 75(19), 6689-6692.

Pent-4-ynyl tert-butyl N,N-diisopropyl phosphoramidite was synthesized quickly and easily using pent-4-yn-1-ol and tert-butyl tetraisopropylphosphorodiamidite as starting material and diisopropylammonium tetrazolide as activator. Subsequently, pent-4-ynyl tert-butyl N,N-diisopropyl phosphoramidite was attached to the 5'-terminus of the oligonucleotides to create a phosphite triester bond. This bond converts into an H-phosphonate diester linkage when treated with dichloroacetic acid. Following this, a reaction involving amidative oxidation using CCl4 in the presence of an amine, along with a 1,3-dipolar cycloaddition with an azide catalyzed by copper(I), resulted in the efficient synthesis of bis-conjugated oligonucleotides.
Synthesis of pent-4-ynyl tert-butyl N,N-diisopropyl phosphoramidite
A solution of pent-4-yn-1-ol (168 mg, 2.0 mmol) and tert-butyl tetraisopropylphosphorodiamidite (731 mg, 2.4 mmol) in anhydrous dichloromethane (10 mL) was treated with diisopropylammonium tetrazolide (172 mg, 1.0 mmol). The mixture was stirred at room temperature overnight, then diluted with ethyl acetate (50 mL) and washed with brine (2100 mL). The organic phase was dried over Na2SO4, filtered, and concentrated to dryness. The resulting residue was purified using flash column chromatography (on silica gel with isocratic elution of cyclohexane containing 5% Et3N), yielding phosphoramidite product 1 (430 mg, 75% yield) as a colorless oil.