Chiral Quaternary Phosphonium Salts

K. Manabe, Asymmetric Phase-Transfer Alkylation Catalyzed by a Chiral Quaternary Phosphonium Salt with a Multiple Hydrogen-Bonding Site , Tetrahedron Lett. 1998, 39, 5807-5810. 

K. Manabe, Synthesis of Nobel Chiral Quaternary Phosphonium Salts with a Multiple Hydrogen-Bonding Site, and Their Application to Asymmetric Phase-Transfer Alkylation , Tetrahedron 1998, 54, 14465-14476. 

Manabe has prepared the chiral quaternary phosphonium salt 17 with a multiple hydrogen bonding site this salt accelerates the alkylation of the ketoester 18, giving products such as 19 with ca. 40% ee at room temperature (Scheme 6) [13]. 

In 2009, the phosphonium-derived catalyst 122 was utilized by Maruoka and co-workers [66]. The group aimed to construct chiral quaternary carbon centers and set out to explore the scope of these particular phase-transfer catalysts, since they successfully employed chiral quaternary phosphonium salts before. The catalyst... 

In contrast to the broad synthetic utility of chiral quaternary ammonium salts in PTC, the application of chiral quaternary phosphonium salts as phase-transfer catalysts remains poorly studied, and only a few special examples have been reported so far with limited success. In 1998, Manabe prepared the chiral phosphonium salt... 

Figure 12.14 Chiral quaternary phosphonium salt phase-transfer catalysts.

Alkylation of phthalimide anion can be carried out under solid-liquid phase-transfer conditions, using phosphonium salts or ammonium salts. In the reaction systems using hexadecyltributylphosphonium bromide, alkyl bromides and alkyl methanesulfonate are more reactive than alkyl chlorides. Octyl iodide is less reactive than the corresponding bromide and chloride. ( )-2-Octyl methanesulfonate was converted into (S)-2-octylamine with 92.5% inversion. Kinetic resolution of racemic ethyl 2-bromopro-pionate by the use of a chiral quaternary ammonium salt catalyst has been reported. Under liquid-liquid phase-transfer conditions, A -alkylation of phthalimide has been reported to give poor results. ... 

In addition, chiral nitrogen-substituted quaternary stereocenters can be accomplished by using 1,3-dicarbonyliccompounds as substrates in the direct a-amination process. Thus, several cyclic (i-ketoesters 46 (Scheme 27.9) were submitted to electrophilic amination under phase-transfer conditions catalyzed by the chiral binaphthyl phosphonium salt 47 [50a], Different substituents on the aromatic ring were tolerated, but lower yields were obtained using a six-membered ring cyclic... 

Cathodic deprotection of tosylates of chiral alcohols was achieved without racemization by cleavage of the O—SO2 bond [351]. Optically active quaternary arsonium [352, 353] and phosphonium salts [354] are cathodically cleaved to tertiary arsines and phosphines respectively, with retention of the configuration. The first enantiomer enriched chiral phosphines have been prepared this way. 

Apart from these well-known catalysts, much effort has been expended in the synthesis and applications of chiral phase-transfer catalysts that include various quaternary ammonium salts, metal-salen complexes, phosphonium salts, and chiral amines. However, few of these catalysts have shown promising levels of asymmetric induction in asymmetric reactions. 

Reactions of Phosphonium Salts.— Asymmetric induction is observed on alkaline hydrolysis of the prochiral phosphonium salts (132) under phase-transfer conditions in the presence of an optically active quaternary ammonium salt, forming the chiral oxides (133) with a 0—8 % enantiomeric excess. Alkaline hydrolysis of monobenzyl quaternary salts of a,co-bis(diphenylphosphino)alkanes gives a route to diphosphine monoxides, e.g., (134). Aqueous hydrolysis of (dibromo-fluoromethyl)triphenylphosphonium bromide gives a high yield of dibromo-fluoromethane and triphenylphosphine oxide. When the reaction is carried out in the presence of radiolabelled Br, the evidence points to the involvement of the dibromofluoromethyl carbanion, and not to a carbene intermediate as was observed in the reaction of the related (bromodifluoromethyl)phos-phonium salt. ... 

A new route to optically active trialkylphosphine oxides, and hence phosphines, has been reported. The key step, the conversion of the optically active phos-phinite (4) to phosphine oxide, is extremely sensitive to the solvent mixture used, and even under the most favourable conditions involves considerable racemization. Small levels of optical activity (0—8 % enantiomeric excess) have been induced in the phosphine oxide product by hydrolysis of the phosphonium salt (5) under phase-transfer conditions using optically active quaternary ammonium salts as chiral catalysts. ... 

Over the past decades, quaternary ammonium- and phosphonium salts have been widely employed as effective phase-transfer catalysts in reactions between snb-stances located in different immiscible phases. Recently, efforts have been made to unlock the full potential of chiral non-racemic onium salts as versatile catalysts for asymmetric carbon-carbon bond formation. These reactions can be condncted nnder mild biphasic conditions and the phase-transfer catalysts can often be derived from readily available naturally occurring alkaloids. The reaction proceeds since the catalyst forms a well-defined chiral ion pair with the electrophile. As a result one enantiotopic face is shielded and enantioselective carbon-carbon bond formation can be realized. 

The construction of a quaternary chiral center in 3-aryloxindoles 209 is of interest, since this structure is present in several biologically and pharmaceutically active compounds. Newly designed phosphonium salt 208 catalyzes the Mannich reaction between 3-aryloxindoles (206) and activated imines (207) in quantitative yields with excellent diastereoselectivity and high enantioselectivity under phase-transfer conditions (Scheme 28.26) [105]. 

Chiral onium salts, such as chiral quaternary ammonium and phosphonium salts, are the predominant choice for asymmetric PTC. The onium salt-triggered PTC is beheved to proceed via the formation of catalyst-substrate ion pairs. High enantioselectivity could be achieved if the chiral cation was designed with effective structural features. 

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