Transition Metal-Catalyzed Asymmetric Reactions Using P-Chirogenic Diaminophosphine Oxides: DIAPHOXs

Abstract

This review describes the development of a new class of chiral phosphorus ligands: amino acid-derived Pchirogenic diaminophosphine oxides, DIAPHOXs, and their application to several transition metal-catalyzed asymmetric allylic substitution reactions. Pd-catalyzed asymmetric allylic alkylation with cyclic b b-keto esters as prochiral nucleophiles was initially examined using P-chirogenic diaminophosphine oxide 1a, resulting in highly enantioselective construction of quaternary stereocenters. Mechanistic investigations revealed that 1a is activated by N,O-bis(trimethylsilyl)acetamide-induced tautomerization to afford a trivalent diamidophosphite species 13, which functions as the actual ligand. Pd-catalyzed asymmetric allylic substitutions of both acyclic and cyclic substrates were also examined using various nucleophiles such as malonate derivatives, nitromethane, aliphatic amines, and aromatic amines, providing a variety of chiral compounds with good to excellent enantioselectivity. In addition, Ir-catalyzed asymmetric allylic amination and alkylation of terminal allylic carbonates were examined using structurally optimized P-chirogenic diaminophosphine oxides, and the corresponding branched products were obtained in a highly regio-and enantioselective manner. Furthermore, the developed catalytic asymmetric process was successfully applied to the catalytic enantioselective synthesis of biologically active compounds, (R)-preclamol, (R)-baclofen hydrochloride, and (؊)-paroxetine.

Coordination chemistry and catalysis with secondary phosphine oxides

“…An elegant synthesis of a HASPO with an stereogenic phosphorus atom was reported by Hamada and co-workers (Scheme 11). 10,[43][44][45] In this methodology, L-aspartic acid was converted in a few steps into a chiral triamine. A diastereoselective formation of the corresponding triaminophosphine using PCl3, followed by the subsequent hydrolysis yielded the desired diaminophosphine oxide (DIAPHOX).…”

Straightforward Diastereoselective Synthesis of P-Chirogenic (1R)-1,8,8-Trimethyl-2,4-diaza-3-phosphabicyclo[3.2.1]octane 3-Oxides: Application as Chiral NMR Solvating Agents

“…The principal investigation was performed with symmetric secondary substituted compound 16 and the addition of 4 equiv BSA to toluene‐D 8 . The experiment was controlled at different times; however, the best result was obtained after 24 h. The reaction was much slower compared to five‐membered ring diaminophosphine oxides like DIAPHOX 5 . The 31 P NMR showed that pentavalent ligand 16 (chemical shift: 8.1 ppm, toluene‐D 8 ) reacted with BSA to provide the formation of a trivalent phosphorus species (chemical shift: 117.4 ppm, toluene‐D 8 ) (Fig.…”

“…15 , 1H, H-1 ), 3.78 -3.74 (m, 2H, H-1 , H-3 21 (m, 2H, H-4), 1.81 -1.72 (m, 2H, H-5), 1.38 (s, 3H, H-8), 1.14 (s, 3H, H-6), 1.05 (s, 3H, H-7) ppm. 13 (14). Prepared from monoarylated diamine (0.30 g, 1.02 mmol), triethylamine (0.17 mL, 1.22 mmol) and 2,4,6-trimethylbenzyl chloride (0.19 g, 1.12 mmol) in acetonitrile (10 mL).…”

“…One relevant class of P‐stereogenic diaminophosphine oxides was discovered by Hamada and co‐workers. They synthesized a new class of P‐chirogenic phosphine oxides based on a chiral asymmetric diamine framework, called P‐stereogenic diaminophosphine oxides: DIAPHOXs 5 . These chiral ligands with a stereogenic center on a phosphorus atom have been prepared from ( S )‐aspartic acid .…”

The Synthesis of Chiral Phosphorus Ligands for use in Homogeneous Metal Catalysis

“…[112] Pioneering work came from Nemoto, who reviewed recently the main aspects of diaminophosphine oxides (DIAPHOX, Figure 8) in transition metal-catalyzed asymmetric reactions. [113] The groups of Pugin and Pfaltz synthesized mixed secondary phosphine oxides/phosphines called JoSPOphos, owing to their similarity to the well established family of JosiPhos ligands (Schemes 45 and 54). [114] In the first step Ugi-amine was brominated.…”