1,3,2-Diazaphospholidines reactions

A highly diastereoselective exchange reaction between a variety of bis(dimethy-lamino)arylphosphines and (S)-2-(anilinomethyl)pyrrolidine (197a) and its SV-aryl analogues constituted a key step in the synthesis of a series of substituted monodonor diazaphospholidine ligands, 213-220 [90, 91] (Figure 1). 

This methodology was applied successfully also for the diastereoselective synthesis of a series of P-stereogenic (o-hydroxyaryl)diazaphospholidine - borane complexes 250-257 (yields ranging from 40 to 86%) via the reaction sequence shown in Scheme 61 with a one-pot formation of the appropriate (o-bromoaryloxy) diazaphospholidine-borane complexes 242-249 in yields ranging from 70 to 92% (Scheme 61) [93],... 

More powerful than the Anderson-Shapiro reagent is the diazaphospholidine reagent developed by Alexakis and co-workers37 39. The reagent is easily prepared by amine exchange of p[N(ch3)2]3 with (R,R) N,A -dimethylcyclohexane-l,2-diamine in refluxing toluene. It must be stored as an 0.2 M solution under nitrogen. The reaction with the analyte alcohol is run in the NMR tube at room temperature. 

Various l,3,2-diazaphospholidin-4-thione-2-sulfides 91 were prepared in moderate yield by the reaction of 3-substituted glycinamides 89 with Lawesson s reagent 90 in benzene at 55-60°C (Equation 6) <1999HAC105, 1997PS(129)111>. A similar procedure based on the reaction of Lawesson s reagent 90 with a-aminonitriles was used for the synthesis of 1,3,2-diazaphospholidine-4-thione 2-sulfide derivative 92 <2001S2445>. 

Complexation of the latter at phosphorus with borane, followed by methanolysis of the siloxyether function, gives the related o-hydroxyaryl diazaphospholidines. The cage-like triaminophosphine (109) has been obtained from the reaction of tri(2-pyrrolyl)methane with phosphorus trichloride, in the presence of triethylamine. This compound is stable to methanolysis, hydrolysis, and aerial oxidation at room temperature. Phosphorylation of various 1,2,4-triazoles with halophosphines has given a route to the heterocyclic system (110), and routes to various [2,4,l]benzodiazaphosphinines, e.g., (Ill), have also been developed. ... 

There have been several modifications to the Corey-Winter reaction, the most significant of which was published by the Corey group in 1982.9 Corey and Hopkins reported that by using a diazaphospholidine in place of trimethylphosphite, thionocarbonates could be converted to the corresponding olefins at significantly lower temperatures. Thus, thionocarbonate 20 was prepared from diol 19 in 93% yield, and subsequent treatment of 20 with diazaphospholidine 21 afforded olefin 22 in 88% yield. Several complex examples were disclosed in which olefins were generated in 70-94% yield.9... 

The Corey-Winter reaction has found use in complex natural product synthesis. In one example, treatment of thionocarbonate 26 with diazaphospholidine 21 afforded diene 27 in 82% yield. This diene was ultimately used in a total synthesis of (-)-taxol.14... 

Hydroxyalkyl and Epoxyalkyl Acids. - The reaction most widely adopted for the preparation of (l-hydroxyalkyl)phosphonic esters is that attributed to Abramov and involves the interaction of hydrogenphosphonates with aldehydes or ketones, sometimes in the presence of a base catalyst. The same reaction has now been shown to be catalysed by mineral phosphates e.g. fluoroapatite. The same process, catalysed by the complex (134) [(R)-form] gives the same esters in 50-95% yields and with 55-9d% e.e.s The study of the diastereoselective phosphonoylation of aldehydes using chiral 1,3,2-diazaphospholidine reagents has continued with an examination of the use of the stereoisomers of (135), which... 

Following a treatment with one equivalent of BuLi, the phosphorodiamidate (63) (R = PhO) undergoes dehydrochlorination to give the mono-aziridide (64) neither a further reaction to give the bis-1-aziridide, (65), nor cyclization to give the 1,3,2-diazaphospholidine (66), is observed, even in the presence of an excess of BuLi. Compound (64) is thus isolable in pure form. This behaviour is in contrast to that demonstrated by (63)(R = Ph) for which the conversion of (64) into (65) is faster than that of (63) into (64). (It might be noted that the P(0)-N bond is not immune to attack by... 

From Table 3.1 it can be seen that both monodentate (entries 1-24) and P,N-bidentate (entries 25 32) ligands can be prepared. Entry 33 depicts a polymer-bound diazaphospholidine, prepared by reaction of 4 with poly(p-hydr-oxystyrene). The stereoselectivity is often very high towards the thermodynamic anti epimer but sometimes significant amounts of the other epimer at the phosphorus atom are obtained (entries 9, 12, 13, 17, 21 and 32). The observed selectivity suggests that a dynamic kinetic resolution takes place during the reaction of 4 with alcohols or amines. ... 

Diazaphospholidines have been successfully applied as ligands in several transition metal-catalysed reactions. In addition, some have been subjected to further transformations (Scheme 3.4) to yield diazaphospholidine boranes 6 and some P(V) compounds oxides 7, sulfides 8 and iminophosphines 9. Most of the reactions have been found to proceed with complete retention of configuration at the phosphorus atom. 

The diazaphospholidine oxide group activates the ortho position towards metallation (Scheme 3.7) creating the stabilised carbanion 14, which intramo-lecularly attacks the phosphorus atom producing the product 13. It has been suggested that the driving force of the reaction is the extra stabilisation of the lithium cation by two oxygen atoms in 13 compared to only one in 12. ... 

The reaction has been extended to diazaphospholidine boranes (Scheme 3.10). In this case, the presence of bromine in the ortho position is needed to allow the formation of the carbanion, which subsequently attacks the phosphorus centre. In addition, the reaction was found to be completely stereoselective, once more with retention of configuration at the phosphorus atom. It has to be mentioned that the reaction does not work for unprotected diazaphospholidines. 

Because vicinal dibromides are usually made by bromination of alkenes, their utility for synthesis is limited, except for temporary masking of a double bond. Much more frequently, it is desirable to convert a diol to an alkene. Several useful procedures have been developed. The reductive deoxygenation of diols via thiocarbonates was developed by Corey and co-workers. Triethyl phosphite is useful for many cases, but the more reactive reductant 1,3-dimethy 1-2-phenyl-1,3,2-diazaphospholidine can be used when milder conditions are required. The reaction presumably occurs by initial P-S bonding... 

The use of the highly crystalline diazaphospholidines (55) as derivatives for the characterization of alcohols has been reported the preparation and other applications of (55) are discussed later in this Report ( Preparation of Halogeno-compounds ). Full details have appeared of the nucleophilic substitution of the oxygen atom of primary and secondary alcohols by way of [2]-, [3]-, and [4]-betylates (56 = 2,3, and 4, respectively) (4, 158). The reactions of the... 

Isopropylidenedioxy-substituted BCOD-fused pyrrole 52d was deprotected to afford the dihydroxy derivative, which was transformed via cyclic thiocarbonate by treatment with thiocarbonyldiimidazole to bicyclo[2.2.2]octatriene-fused (BCOT-ftised) pyrrole 54 by l,3-dimethyl-2-phenyl-1,3,2-diazaphospholidine [57]. Quadmply BCOT-fused porphyrin 55 was obtained in 66% yield by the usual cyclic tetramerization method [58]. In this reaction, an interesting by-product, triply BCOT-fused porphyrin, was obtained in a very small amount. This by-product was thought to be formed by the rDA reaction of intermediates during the oxidation of porphyrinogen to porphyrin [59]. 

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