Phospholanes substituted

The pioneering work of Denney et ai19 on the synthetic utility of oxyphosphoranes has been thoroughly exploited by Evans et al. in demonstrating that diethoxytriphenylphosphorane promotes mild and efficient cyclodehydration of diols (e.g. 11) to cyclic ethers (e.g. 13) via the cyclic phosphorane (12)20>21. Simple 1,2-, 1,4-, and 1,5- diols afford good yields of the cyclic ethers but 1,3-propanediol and 1,6-hexandiol give mainly 3-ethoxy-l-pro-panol and 6-ethoxy-l-hexanol respectively whereas tri- and tetra-substituted 1,2-diols afford the relatively stable 1,3,2- diox-phospholanes. In some instances (e.g. 14), ketones (e.g. 16) are formed by a synchronous 1,2-hydride shift within (15). The synthetic utility has been extended to diethoxyphosphoranes supported on a polystyrene backbone22. 

The fundamental discovery by Burk et al. that the analogous trans-2,5-disub-stituted phospholanes formed a more rigid steric environment led to the introduction of the DuPhos and BPE ligand classes (Fig. 24.1) [8-13]. Subsequently, these ligands have been successfully employed in numerous enantiomeric catalytic systems [4 a, 5], the most fruitful and prolific being Rh-catalyzed hydrogenations. The reduction of N-substituted a- and /1-debydroarnino acid derivatives,... 

The group of Salzer has recently reported phospholanes 54-56 based on chiral half-sandwich complexes [79]. These were obtained by treatment of the appropriately substituted complex with a secondary phospholane, itself accessed via the cyclic sulfate or dimesylate and PH3. These were tested against a range of substrates with C=C, C=0 and C=N bonds, with variable results [80]. 

Realising that the bite angle was important in these ligands, a chiral ligand in the Xantphos series has been developed [4], which contains the phospholane moiety discovered by Burk as the chiral entity (Fig. 13.8). This ligand turned out to be very useful in several common allylic substitution reactions (1,3-dimethylallyl, 1,3-diphenylallyl, cyclohex-2-ene-l-yl) and kinetic resolution. 

Inversion at phosphorus in 2,3-diphenyl-2,l,3-germa(II)- and 2,3-diphenyl-2,l,3-germa(IV)-diphospholanes as well as in l-tert-butyl and 1-phenyl-substituted 2,5,l-digerma(IV)-phospholanes was studied by H and P dynamic NMR spectroscopy <82JOM(224)247>. 

Racemic a-phenylethyl bromide is carbonylated under phase-transfer conditions with 5 N NaOH and dichloromethane containing bis-(dibenzylideneacetone)Pd(O) and a chiral 2-substituted 3,1,2-oxaza-phospholane to give a-phenylpropionic acid in moderate ee (Scheme 83) (196). The reaction involves kinetic resolution of the bromide with a discriminative slow oxidative addition step. 

To improve the preparative method of phospha sugars from sugar starting materials [21,22], the Arbzov reaction and Grignard coupling reaction have been applied to a reaction of 1,4-dibromobutane. The reaction of 1,4-dibromobutane (53) with dimethyl phenylphosphonite to give ethyl (4-bromobutyl)phenylphosphinate (54) and successive intramolecular substitution of the 4-bromo substituent with phosphinyl anion affords 1-phenyl -phospholane 1-oxide (56a) in 40% yield. It can also be prepared from... 

Fig. 14 2-Uncyclized substituted uracil phospholane derivatives 121d-g...

The stereochemistry of the addition has been recognized on the basis of structural features and chemical behavior of the complexes 9, produced in selected reactions of j with 1-ethoxy-1-oxo-2-phospholene 8. Neutralization of these complexes gave exclusively cis-3-substituted phospholane oxides J 0 while alkylation resulted in stereoselective formation of cis-3, cis- -disubstituted phospholane oxides JJ. The progress of the latter reaction was strongly dependent on the size of the alkyl groups involved. 

The use of phosphide nucleophiles in an SN2 attack on alkyl-substituted cyclic sulfates allows access to a wide range of phospholane derivatives. However, if aryl-substituted cyclic sulfates are used, elimination and racemization processes compete with substitution. To access bis(2,5-diphe-nylphospholano)ethane (4), an alternative strategy was required (Scheme 13.2).14... 

A -Dioxaphospholanes show no inversion at the phosphorus atom, which can be seen in the nonequivalence of the CFj groups (273). A -Dioxaphospholanes 73 can be oxidized with halogens to form A -dioxaphospholanes 74 (228). Exchange of the halogens in 73a-c with suitable reaction partners (e.g., LiNHj) yields substituted A -phospholanes [e.g., 73g (265)] (see also Section III,A,2). 

Historically, phospholanium salts have been prepared by quaternization in high yield of a selected phospholane with an alkyl halide. Although numerous methods exist for the preparation of the desired phospholanes (recently reviewed ), most of these have major drawbacks, including (1) very critical conditions, such as reaction time, dilution effects, and temperature (2) expensive and/or difficult to manipulate reagents and (3) the necessity of a multistep synthetic sequence giving overall low yields of phospholane. A general example of the latter would be the reaction of a substituted dihalophosphine with a 1,3-diene and hydrolysis to the phospholene oxide, which then can be catalytically reduced to the phospholane oxide and subsequently converted to the phospholane. ... 

Displacements involving allylic systems. Allylic substitution reactions continue to receive considerable attention. Improvement by microwave is noted. " New ligands for the Pd-catalyzed reaction include iminophosphine 13, which is derived from 1-mesitylethylamine, pyridylphenylphosphine 14, and the phosphinite 15, obtained from D-glucosamine. Phospholanes such as 16, 17, 18, prepared from mannitol, are excellent ligands. 

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