A phosphetane is a 4-membered organophosphorus heterocycle. The parent phosphetane molecule, which has the formula C3H7P, is one atom larger than phosphiranes, one smaller than phospholes, and is the heavy-atom analogue of azetidines. The first known phosphetane synthesis was reported in 1957 by Kosolapoff and Struck, but the method was both inefficient and hard to reproduce, with yields rarely exceeding 1%. A far more efficient method was reported in 1962 by McBride, whose method allowed for the first studies into the physical and chemical properties of phosphetanes. Phosphetanes are a well understood class of molecules that have found broad applications as chemical building blocks, reagents for organic/inorganic synthesis, and ligands in coordination chemistry.
Synthesis Many methods towards the synthesis of phosphetanes have been developed since 1957. The following are the most utilized.
McBride method (Electrophilic addition to olefins) The method initially outlined by McBride has been developed for singular alkenes, as well as dienes. Both types follow the same general mechanism: formation of a phosphenium cation from a dichlorophosphine and aluminum trichloride, electrophilic addition by an alkene to the phosphenium, carbocation rearrangement, intramolecular nucleophilic addition of the new alkyl phosphine to the carbocation, and oxidation of the resulting phosphetanium with water to obtain a phosphetane oxide. Limitations of this approach are unpredictable carbocation rearrangement in more complexly branched alkanes, the incompatibility of carbocations with many nucleophilic functional groups, and the risk of cation quenching by elimination pathways.
Mono-ene addition In the case of electrophilic addition to a single alkene, carbocation rearrangement occurs via hydride or alkyl shifts. The general scheme for phosphetane synthesis from mono-enes is given below:
Diene addition In the case of electrophilic addition to a diene, carbocation rearrangement first occurs via cation-π cyclization. The general scheme for phosphetane synthesis from dienes is given below:
Alkylation and intramolecular cyclization Alkylation and cyclization pathways have been developed for both phosphines and phosphine oxides.
From phosphines The synthesis of phosphetanes from P(III) alkylation and subsequent cyclization usually proceeds through sequential phosphanide/phosphine displacement of 1,3-alkyl dihalides or sulfonate esters (OTf, OTs, OMs, etc.). The phosphanide source is commonly the lithium salt, but can also be accessed by in situ deprotonation of phosphines. The SN2 mechanism associated with this transformation comes with the advantage of stereospecificity, but at the expense of electrophilic or epimerizable functional group tolerance and kinetically slow reactivity with secondary/tertiary leaving groups. The general mechanism is seen below:
From phosphine oxides Similar syntheses from P(V) compounds are known but are far rarer due to their relative inefficiency and unpredictability. This preparation features the in situ formation of a Grignard reagent, followed by intramolecular addition/cyclization to a phosphine oxide, all on an n-propyl backbone. This was the method employed by Kosolapoff and Struck in the first synthesis of a phosphetane. The general mechanism is seen below:
Cyclopropane ring-expansion Another way to make phosphetanes comes from the ring-expansion of cyclopropanes, in which it seems a phosphine is directly inserted into a C-C bond. The true mechanism of this transformation is similar to that of the McBride synthesis and is sometimes classified as such, with similar advantages and drawbacks. Although relieving the cyclopropane ring strain is of great assistance in the initial C-P bond, exhaustive alkyl substitution to stabilize the formed carbocation is often required. The general mechanism is seen below:
[2+2] cycloaddition One final method that has been observed to produce phosphetanes is the [2+2] cycloaddition of phosphaalkenes and olefins. This method is not often discussed for its tendency to produce phosphetanes, but rather for its insight into the reactivity of the much more elusive phosphaalkenes. The difficult synthesis of these phosphaalkenes severely limits the utility of the method as it relates to phosphetane synthesis, despite its attractive stereospecific and modular approach. This usually involves a Lewis acid bound phosphorus, and can occur with electron rich phosphaalkenes and electron poor olefins, or the inverse. An example of each, and the mechanism, are seen below:
Structure and bonding Experimental and crystallographic data exists for many types of phosphetanes. The PC3 ring is slightly ruffled. Phosphetane oxides and phosphetanium ions are also known For the oxide, one may expect the HOMO is an oxygen lone pair and the LUMO is largely contributed to by the P-O π-antibonding interaction. Phosphetanes with pentacoordinate P are also called phosphoranes.. Such phosphoranes typically adopt structures approximating trigonal bipyramidal and square pyramidal.
Reactivity Reactivity at the phosphorus center, including reduction, oxidation, and phosphorane formation as well as alkylation of ring carbons can be performed without cleavage of the ring in some instances, representing the final types of inherent reactivity. These four will be discussed in more detail below. Much of the reactivity of phosphetanes is attribute to ring strain, calculated to be ~17.9 kcal/mol. The release of strain energy drive ring expansion and ring opening. The polymerization has only been sparsely observed in very concentrated solutions.
Ring opening accompanies phosphetanium oxidation and α-carbon functionalization.
One intentional and constructive method of ring-opening has been outlined in the literature and features a phosphetane ylide that undergoes Wittig reactivity with aldehydes to form γ-unsaturated phosphine oxides.
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