At phosphorus

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. 

The second problem concerns isomers of these various systems. As illustrated, 2d might be presumed to be planar. Unlike nitrogen, the inversion at phosphorus is very slow and there are, in fact, five possible isomers of it (three meso and two dl pairs). The interconversion of these isomers is reported in a subsequent paper by Davis, Hudson and Kyba along with x-ray crystallographic data on the structure of the so-called isomer B . 

A similar situation occurs in trivalent phosphorus compounds, or phosphines. It turns out, though, that inversion at phosphorus is substantially slower than Inversion at nitrogen, so stable chiral phosphines can be isolated. (R)- and (5)-metbylpropylphenylphosphine, for example, are configurationally stable for several hours at 100 °C. We ll see the Importance of phosphine chirality in Section 26.7 in connection with the synthesis of chiral amino adds. 

Chapter 9, Stereochemistry —A discussion of chirality at phosphorus and sulfur has been added to Section 9.12, and a discussion of chiral environments has been added to Section 9.14. 

Other cyclizations at phosphorus have been observed when certain phosphinates were used in the acid-catalyzed Mannich reaction. As observed previously with various phosphonous acid derivatives, reaction of aliphatic phosphinic acids with primary amines favored the formation of 2 1 adducts (73). Thus, glycine and other a-amino acids reacted under the typical conditions with excess formaldehyde and alkyl phosphonous acids to give the bis-phosphinylmethyl adducts 125. 

Significant advance in the field of asymmetric catalysis was also achieved with the preparation of l,2-bis(phospholano)benzene (DuPHOS 4) and its confor-mationally flexible derivative (l,2-bis(phospholano)ethane, known as BPE) by Burk et al. [59]. Two main distinctive features embodied by these Hgands, as compared to other known chiral diphosphine ligands, are the electron-rich character of the phosphorus atoms on the one hand and the pseudo-chirality at phosphorus atoms, on the other. These properties are responsible for both the high activity of the corresponding metal complex and an enantioselection indepen-... 

We discovered a complementary procedure for conversion of OMen to other functional groups. The ester P-OMen bond was shown to be cleaved in a stereoselective manner reductively [85,86]. The cleavage takes place with almost complete preservation of stereochemical integrity at phosphorus. The reducing agents are usually sodium or Hthium naphthalenide, lithium biphenyUde, and Hthium 4,4 -di-fert-butylbiphenyl (LDBB). The species produced is then quenched with an alkyl hahde or methanol to afford tertiary or secondary phosphines, respectively (Scheme 5b). Overall, the displacement reaction proceeds with retention of configuration. 

The product of bis-coordination, 20 at phosphorus, could be also achieved utilizing the more nucleophilic p-dimethylamino pyridine (DMAP) [57, 58]. As shown in Scheme 12,bis-coordination of the two donors occurs in general by taking up the two orthogonal positions of the PN 7i-bonds [58]. 

The rearrangement has also been extended to P-chiral S-phenyl phos-phinothiolate 79 and 0-phenyl phosphinothioate 80 (Scheme 21). With these asymmetric compounds, the C-P bond formation was found to occur stereose-lectively and with retention of configuration at phosphorus [51]. 

Although sulfur is unHkely to chelate the metal in this case, it is worth mentioning the axially chiral diphosphine Hgands, based on hz-thienyl systems which increase the electronic density at phosphorus such as 159 (used in Ru-catalyzed reduction of /1-keto esters with 99% ee) [llla],BITIANP 160,andTMBTP 161 (in a Pd-catalyzed Heck reaction, the regio- and enantioselectivity are high with 160 but low with 161) [mb]. 

Finally, two more anionic phosphate anions with six oxygen substituents at phosphorus (Fig. 5) were isolated by serendipity. Compound 25 [43] was isolated from the reaction of naphthalene-2,3-diol and phosphonitrilic chloride in... 

Stereo studies involving spirophosphoranyl biradicals showed that the rearrangement occurs with almost complete retention of configuration at phosphorus (Scheme 29) [66,67]. 

The stability of phosphinous amides depends, to a large extent, on the substituents at phosphorus and nitrogen. Normally, tetrasubstituted and N,P,P-trisubstituted phosphinous amides are stable and well-known compounds. The parent compound H2PNH2 is a volatile compound that is formed on hydrolysis of a solid state solution mixture of magnesium phosphide and magnesium... 

NH-Phosphinous amides are also alkylated at phosphorus by electrophilic olefins, such as acrylonitrile and acrylamide, with concomitant formation of a... 

Tetrasubstituted phosphinous amides of the type R2NPPh2 have been successfully arylated at phosphorus by the action of bromobenzene, in a process catalyzed by NiBr2, to give the aminophosphonium bromides [R2NPPh3] Br [109]. Other representative members of this class form phosphane-borane complexes [62], are aminated at phosphorus by chloramine to yield bis(amino)phos-phonium salts [110] and have been claimed to be protonated at phosphorus by ethereal tetrafluoroboric acid, as determined by NMR analysis [111]. 

The same fluoroalkoxy substituents, however, are able to enhance substitutional reactivity of fluorinated polyphosphazenes by originating methatetical exchange reactions on polymers in the presence of new nucleophiles and under appropriate experimental conditions. Thus, a series of exchange reactions at phosphorus atoms bearing the trifluoroethoxy substituents in PTFEP have been describedbyH.R. Allcock [508] (Fig. 13),Cowie [482,483] (Fig. 14), and Ferrar [509] (Fig. 15), while surface modification of PTFEP films were reported by Allcock [514,515] (Fig. 16 or 17) and by Lora [516] (Fig. 18). 

Reduction of 1-benzyl-3,4-dibromophospholan oxide (125) with tri-chlorosilane, followed by debromination, gave 1-benzylphosphole. Determination of the molecular structure by X-ray analysis showed slight puckering of the ring with retention of pyramidal configuration at phosphorus. ... 

The cage-like phosphonium salt (17) with phenyl-lithium in THF gave the phosphorane (18) which probably owes its great stability to the relief of strain in the ring structure on changing the bond angle at phosphorus to 90°. For the photolysis of (18) see Chapter 10, Section 1. 

B. Reactions.—(/) Nucleophilic Attack at Phosphorus. A reinvestigation of the reaction between phosphorus trichloride and t-butylbenzene in the presence of aluminium chloride has shown that the product after hydrolysis is the substituted phosphinic acid (11), and not the expected phosphonic acid (12). Bis(A-alkylamino)phosphines have been reported to attack chlorodiphenyl phosphine with nitrogen, in the presence of a base, to give bis-(A-alkyl-A-diphenylphosphinoamino)phenylphosphines (13). In (13), the terminal phosphorus atoms are more reactive than the central one towards sulphur and towards alkyl halides. 

C. By Oxidation.—This year s literature has been notable for attempts to study the details of certain phosphine oxidation reactions. In one such investigation nitric acid was found to oxidize phosphines, or phosphine sulphides, to phosphine oxides with inversion of configuration at phosphorus, whereas dinitrogen tetroxide, in the absence of acid, was found to oxidize the same compounds with predominant retention. The partial racemization observed with the latter reagent was probably due to the racemization of the oxides, since methylphenyl-n-propylphosphine oxide... 

Two contrasting conclusions have been reported in the reactions of lithium aluminium hydride in THF with phosphine oxides and phosphine sulphides respectively. The secondary oxide, phenyl-a-phenylethylphos-phine oxide (42), has been found to be racemized very rapidly by lithium aluminium hydride, and this observation casts some doubt on earlier reports of the preparation of optically active secondary oxides by reduction of menthyl phosphinates with this reagent. A similar study of the treatment of (/ )-(+ )-methyl-n-propylphenylphosphine sulphide (43) with lithium aluminium hydride has revealed no racemization. These results have been rationalized on the basis of the preferred site of attack of hydride on the complexed intermediate (44), which, in the case of phosphine oxides (X = O), is at phosphorus, and in the case of the sulphides (X = S), is at sulphur. Such behaviour is comparable to that observed during the reduction of phosphine oxides and sulphides with hexachlorodisilane. ... 

Russian workers have shown that alkylation of the P" derivatives (13) with triethyloxonium fluoroborate takes place at phosphorus rather than... 

D. Cyclic Esters of Phosphorous Acid.—There has been some controversy about the stable stereochemistry at phosphorus in cyclic phosphites and phosphonites this now appears to be resolved by agreement in a series of papers. The stereochemistry of 2-alkoxy-4-methyl-l,3,2-dioxaphosphorins... 

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