Phosphonium salts chiral

Although unsynunetrically substituted amines are chiral, the configuration is not stable because of rapid inversion at nitrogen. The activation energy for pyramidal inversion at phosphorus is much higher than at nitrogen, and many optically active phosphines have been prepared. The barrier to inversion is usually in the range of 30-3S kcal/mol so that enantiomerically pure phosphines are stable at room temperature but racemize by inversion at elevated tempeiatuies. Asymmetrically substituted tetracoordinate phosphorus compounds such as phosphonium salts and phosphine oxides are also chiral. Scheme 2.1 includes some examples of chiral phosphorus compounds. 

Alkylation primarily at the phosphorus atom with the formation of a chiral phosphonium salt was proved by an investigation of the interaction... 

The phosphonium salt 21 having a multiple hydrogen-bonding site which would interact with the substrate anion was applied to the phase transfer catalyzed asymmetric benzylation of the p-keto ester 20,[18 191 giving the benzylated P-keto ester 22 in 44% yield with 50% ee, shown in Scheme 7 Although the chemical yield and enantiomeric excess remain to be improved, the method will suggest a new approach to the design of chiral non-racemic phase transfer catalysts. 

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. 

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. 

M)-[ll]-, and (M)-[13]-helicene 31). Wittig reactions between (M)-(—)-formyl-hexahelicene and suitable phosphonium salts led to 1,2-disubstituted ethylenes, all containing the same chiral moiety, which could be subjected to photocyclodehydrogenation (Table 1). 

The enantioselective synthesis of a somewhat more complex renin inhibitor starts with the reduction of the ester group in the chiral amino-ester (19-1) by means of diisobutyl aluminum hydride in the cold. The aldehyde product (19-2) is then reacted with prior isolation with the ylide from phosphonium salt (19-3) and a strong base... 

Most of the problems related to the phosphonium salts stereochemistry are discussed under synthesis (Section II), reactivity (Section III) and spectrometric characteristics (Section I.C.). Because of the tetrahedral geometry of phosphorus, chirality arises from the presence of four different substituents. Enantiomeric forms may be separated by... 

The alkylation of tertiary phosphines is, in general, compatible with elaborate structures bearing various functions or chiralities, as illustrated by the preparation of a phosphonium salt (18), intermediate in the synthesis of pseudomonic acid248 (reaction 17). For the preparation of dialkylphosphonium salts, diphenylphosphine can be directly alkylated, but it is more advantageous to use triphenylphosphine as the starting material,... 

This type of disconnection is mainly used for the preparation of dipeptides of type Xaai >[ , CH=CH]Gly. It allows control of the stereochemistry of the Xaa residue by starting from chiral a-amino aldehydes. For the construction of the /ram -p,y-unsaturated carboxylic acid moiety, the use of the triphenylphosphonium salt 31 (Scheme 9) derived from 3-chloro-propanoic acid was not suitable.14 Instead, the trimethylsilylprop-2-ynyl phosphonium salt 33 serves as a three-carbon unit, which can be converted into the P,y-unsaturated acid by hydroboration and oxidation. The required Boc-protected a-amino aldehyde 32 can be prepared using virtually racemization-free procedures. 37 However, at the end of the reaction sequence, racemization has been detected, especially for Boc-Phet )[ , CH=CH]Gly-OH, but not for the Ala and Pro analogues. 63 A mixture of E- and Z-enynes 34 and 35 is formed (8 2 to 9 1), which can be separated by column chromatography. 4,48 50 53 64 65 ... 

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. 

We have simulated the steric course of the alkaline hydrolysis of chiral five- (12) and six- (13) membered cyclic phosphonium salts, whose reaction kinetics and product stereochemistries had been studied previously by Marsi and coworkers (14,15). For this purpose, we determined the absolute configuration of the phospholan-ium iodide (12), and the x-ray structures of the related phos-thorinanium salts, 4 and (13). 

The choice of which way round to do the Wittig may appear arbitrary but it isn t. Pempo and his group7 chose citronellal 47 and citronellol 48, two related natural terpenes from citronella oil, as starting materials with the right stereochemistry at the one chiral centre. If you imagine a Wittig reaction between the phosphonium salt 49 and some suitable aldehyde, you will see that the central part of the molecule would be right. 

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]. 

The synthesis of chiral phosphines from resolved phosphonium salts or phosphine oxides is an intrinsically limited approach. The groups attached to phosphorus must be present prior to resolution and, furthermore, the preparation of phosphine oxides and phosphines from phosphonium salts by chemical or electrochemical cleavage reactions requires that one of the groups bonded to phosphorus be substantially easier to cleave than the other three. 

A stereospecific total synthesis of prostaglandins E3 and F3, containing an additional double bond in this side chain, starts from the optically active phosphonium salt 161. In this synthesis the ( )-13-double bond and the 15-hydroxy function are generated simultaneously by condensation of the chiral bicyclic aldehyde 163 with the P-oxido ylide 162 obtained by treatment of 161 with methyllithium. The corresponding phosphonium salt S) +)-161, already possessing the (Z)-configurated A17-double bond of prostaglandins, was prepared from (S)(—)-tartaric acid 1351 (Scheme 29). 

According to the list of natural carotenoids by O. Straub 38), more than half of the over 400 natural carotenoids described are chiral. The asymmetric optically active terpene phosphonium salts which have recently become known, and which can be employed for the synthesis of chiral carotenoids, are contained in a review article by H. Mayer 47). 

A by now classic retrosynthesis of prostaglandins PGFj and PGEj (Fig, 4) leads to the bicydic lactone [12), five-carbon phosphonium salt [13], and phosphonate [14] (19). These compounds contain all the carbon atoms of the prostaglandins and, in [12], aU but one of the chiral centers. Lactone [12] has come to be knovm genetically as the Corey lactone, and its synthesis in one enantiomeric form has been the subject of numerous complementary investigations. 

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. ... 

This is a very useful route for the preparation of phosphines, especially chiral phosphines. Tertiary phosphine oxides (and sulfides) and phosphonium salts are often precursors of choice in these reduction procedures. The following sections highlight reagents and reaction conditions in forthcoming sections further examples will be given. 

The incorporation of an alkylammonium group can readily be achieved, as for (128), by reduction of the protected tertiary phosphine (as its oxide) with HSiCl3.251 The analogous phosphonium salt (129) is also known.2 2 The chiral quaternized phosphine (130) has been documented,253 whilst protonation of the rhodium(I) complex containing (131) with aqueous HBF4 gave a water-soluble complex.254 Addition of a weak base (NEt3) cleanly reversed this reaction. 

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