Alcohols treatment with phosphorus reagents

The direct replacement of an oxygen, particularly in a carbonyl group, by sulfur is readily achieved by treatment with phosphorus pentasulfide. This is a rather unpleasant reagent, however, since it is readily flammable and upon storage, particularly in a damp atmosphere, it slowly releases the highly poisonous and malodorous hydrogen sulfide. In Protocol 18 typical conditions for its use are illustrated in the synthesis of the chiral thiazoline 74 from the benzoylamino alcohol 73. 

Primary and secondary alcohols are best converted into alkyl halides by treatment with such reagents as thionyl chloride (SOCI2) or phosphorus tribromide (PBrs). These reactions, which normally take place readily under mild conditions, are less acidic and less likely to cause acid-catalyzed rearrangements than the HX method. 

Jsomerides of Morphine and Codeine. When morphine is treated with thionyl chloride, phosphorus trichloride or tribromide, the alcoholic hydroxyl group is replaced by the halogen, forming a-chloromorphide and bromomorphide respectively. The former on treatment with concentrated hydrochloric acid is converted into /3-chloromorphide. Schopf and Hirsch have provided evidence that the two are structural isomerides. With the same reagents codeine yields a parallel set of compounds, viz., a- and -chlorocodides, and bromocodide. The chief characteristics of these products may be summarised thus —... 

Phosphorus oxychloride is a suitable reagent for preparation of the symmetrically substituted phospho-triesters of type (RO)3PO. The preparation is easily achieved by treatment of phosphorus oxychloride with 3 equiv. of alcohols or their metal salts. The reaction is generally promoted by a base or acid. Titanium trichloride is a particularly effective catalyst for the reaction. Conversion of POCI3 to unsymmetri-cally substituted phosphotriesters is achievable with difficulty. Phosphorochloridates and phosphorodichloridates have been used for the preparation of mixed tertiary phosphoric esters of type (ROlmPOfOROn (ffi = 1, n = 2, or m = 2, n = 1) in a very wide variety. Reaction of phosphorus oxychloride and 1 or 2 equiv. of alcohols followed by hydrolysis forms phosphomonoesters or phosphodi-esters, respectively. The hydrolysis may be generally effected by dilute aqueous alkali. Some phosphoFodichlori te intermediates are easily hydrolyzed by water. For example, the phosphorylation of a ribonucleoside (1 equation 4) with phosphorus oxychloride in an aqueous pyridine-acetonitrile mixture furnishes the nucleoside S -monophosphate (2) in excellent yield. ... 

Several related reactions involve the use of phosphorus reagents. Alkyl halides can be made from the treatment of an alcohol with phosphorus halides, PX3 or PX5, as shown in Figure 7.44. Many of these phosphorus-containing reagents cause rearrangement, especially in secondary systems, and the stereochemical outcome, retention or inversion, depends on solvent and other reaction conditions. Accordingly, modifications have been worked out in recent years in order to avoid such stereochemical problems. 

Iodides can be made smoothly from tosylates or bromides by reaction with sodium iodide in acetone.There are also several procedures based on phosphorus reagents which are mechanistically related to those discussed for bromides and chloride. One procedure involves preparation of a cyclic phosphite ester from the alcohol and c -phenylenephosphorochloridite. Treatment of the cyclic phosphite with iodine then generates the alkyl iodide.An alkoxyphosphonium intermediate is involved. 

Petrillo and co-workers developed a highly efficient, one-pot synthesis of protected phosphoamino acids (16), useful building block in the synthesis of phosphopeptides, starting from inexpensive, readily available reagents. Thus, treatment of phosphorus trichloride with alcohol and an amino acid gave the corresponding phosphate intermediates (15), which, after oxidation with bromine-related oxidants afforded phosphoamino acids (16) in moderate to high yields (Scheme 8). ... 

We first sought to convert the primary phosphines into dichlorophosphines (Rg. 1.9) these are typically reactive electrophilic reagents and enantiopure examples would be especially valuable for synthetic operations [36]. A library of phosphonites [58-60] could then be prepared by reaction of these dichlorophosphines with the appropriate alcohols and phenols in the presence of a tertiary amine base, and our exemplar targets were phosphonites based on enantiopure binol as shown in Fig. 1.10. Treatment of (R)-5 and (5)-6 with phosphorus pentachloride [61] in toluene yielded (/ )-16 and (5)-17 in almost quantitative conversion. 

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