Chiral phosphoranes synthesis

The synthesis of an optically active chiral phosphorane in which the optical activity is solely connected with the P atom implies, for instance, the preparation of a trigonal bipyramid or a tetragonal pyramid with five different achiral ligands which would, at least theoretically, entail the possible formation in the first case of ten or in the second case of fifteen diastereoisomers requiring separation, a formidable task even in the absence of stereomutation. The problem has nevertheless been solved using three different approaches exploiting the particular properties of spirophosphoranes, as hereafter detailed. 

Synthesis of Chiral Phosphorane. (5)-(/ )-PPFA has been converted to an enantiomerically pure ferrocenylphosphonium salt... 

An example of chain elongation developed in palytoxin synthesis is given below. As shown in Scheme 11.53, compound 239 was reacted with the chiral phosphorane 240 to furnish the Z isomer... 

Many communications have concentrated on specific amino phosphonic acids or derivative types. Thus, esters of phosphonoaminoacetic add were obtained by the reactions between trialkyl (ethyl) phosphite and (218) and which are thought to proceed via the phosphorane (219). A sequence has been presented for the preparation of the mono- and di-benzyl esters of N-chz protected (a-aminoben-zyl)phosphonic acid. A synthesis of (aminomethylene)bisphosphonic acid from dibenzylamine, dibenzyl hydrogenphosphonate and triethyl orthoformate has been noted and the asymmetric hydrogenation of (220) in the presence of chiral phosphine catalysts yields samples of (221) with e.e.s of 63-96%. The pyrrolidine-based compound (222) has been prepared from methyl S)-N-methoxycarbonyl-4-oxo-2-pyrrolidinecarboxylate and iV-coupled 4-amino-butanal diethyl acetals were the starting materials in syntheses of the pyrrolidine-2-phosphonic add derivatives (223) in which Z represents the iV-protected amino add or peptide moiety. ... 

Despite the overall decline in output, the year has produced ftirther interesting developments in the fteld of hypervalent phosphorus chemistry. These include phosphoranes containing acetylenic links, the synthesis and enantiomeric separation of a bicyclic phosphorane with chirality only at phosphorus, and a wide range of phosphoranes incorporated within macrocyclic ring systems (Houlla et al). In addition Lattman has reported on phosphoranes bound to transition metals or enclosed within calixarene skeletons and Holmes and his co-workers have made further substantial contributions on the X-ray crystal structures of phosphoranes containing eight-membered rings. 

Enzymatic phosphoryl transfer reactions are ubiquitous in nature and play significant roles in ATP hydrolysis and protein phosphorylation processess. As previously described, pentacoordinate phosphorus species have been assumed as transient intermediates or transition states in these pathways and their structural and electronic properties are undoubtedly related to the outcome of the process. Therefore, to aid understanding of the phosphorus-catalyzed biological routes, many model pentacoordinated phosphoranes have been synthesized. While most studies have focused on aspects of apicophilicity, anti-apicophilicity or Berry pseudorotation, there have been limited investigations on the stereochemistry of pentacoordinated spirophosphoranes with a chiral phosphorus atom. In the past year, much attention has been paid to the synthesis and determination of absolute configuration of several chiral pentacoordinate spirophosphoranes derived from D- and L-aminoacids. Some significant achievements in this area will be discussed in this section. 

The Beecham group found that thiols add readily to the double bond of C(2)-unsubstituted 1-carbapenems, and this approach has been used to synthesise racemic PS-5 130). The A -silylated 4-allylazetidinone (157) was alkylated with ethyl iodide and the product (158) transformed to the phosphorane (159). Cyclisation to (1 ) was followed by reaction with acetamidoethane thiol to form three isomers of the addition product (161). These could be converted to the carbapenem (162) on reaction with iodobenzene dichloride in the presence of pyridine. Isomerization to (163) and deprotection afforded the racemic natural product. The ester (163) has also been prepared via the diazo-intermediate (164) derived from the 4-acetoxy azetidinone (165) 131). A total synthesis of chiral PS-5 has been achieved using the resolved acid (166) (132). This was converted to (164) and then to optically pure PS-5. It has also been possible to synthesise PS-5 and PS-7 from the olivanic acid derivatives MM 17880 and MM 13902 133). The benzyl ester of ( )-MM 22381 was obtained from the azabicyc-loheptane (167) derived from the addition of acetamidoethane thiol to the appropriate C(2)-unsubstituted nucleus 108). 

Key steps (Figure 3.3, Scheme 3.2) in the Nicolaou synthesis of ABJ879 (10) are the formation of the C12-C13 double bond via a selective Wittig reaction between phosphorane 11 and aldehyde 12, the stereoselective aldol reaction of ot-chiral aldehyde 13 and ketone 14, macrolactonization of seco acid 16, stereoselective Sharpless epoxidation, to afford the C12-C13 epoxide, and introduction of the heterocycle by means of Stille coupling. ... 

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