Alkoxyphosphonium, salt

In an initial step triphenylphosphine adds to diethyl azodicarboxylate 5 to give the zwitterionic adduct 6, which is protonated by the carboxylic acid 2 to give intermediate salt 7. The alcohol reacts with 7 to the alkoxyphosphonium salt 8 and the hydrazine derivative 9, and is thus activated for a SN2-reaction ... 

Miscellaneous. The reaction of the aminophosphonium salt (156) with thiols and alkoxides affords a convenient, high-yield, single-step synthesis of unsymmetrical thioethers.141 The key intermediate is the alkoxyphosphonium salt (157), which undergoes nucleophilic attack by RS- at the alkoxy carbon. 

The formation of /7-nitro-AW-dimethylaniline (in addition to the expected p-nitrophenyl ether) in the reaction of nitrophenate ion with the alkoxyphosphonium salts (158) indicates the intermediacy of the relatively stable interconverting phos-phoranes (159). Loss of dimethylamide ion gives the salt (160), which subsequently undergoes SurAr reactions.142... 

Selective chlorination or bromination of the 5 -hydroxyl group in unprotected D-ribonucleosides has been achieved75 by treatment with thionyl chloride or thionyl bromide, respectively, in hexamethyl-phosphoric triamide at room temperature for 10-15 hours the 5 -deoxy-5 -halogeno derivatives of cytidine and adenosine have been prepared in this way. The reactions presumably occur by way of alkoxyphosphonium salts as intermediates.78... 

Alkoxyphosphonium salts are a special case, in that they show thermal instability, due to the thermodynamic stability of the P=0 bond formed (reaction 114). This enables them to be isolated only in favourable cases (reaction 114). 

Halophosphonium salts are the useful precursors for the preparation of heteropho-sphonium by ligand exchange, although some relatively stable alkoxyphosphonium salts... 

Substitution of primary and secondary alcohols by SN2 reactions is generally effected according to two protocols, as shown in Scheme 1. The most common approach involves the formation of a sulfonate ester which is an excellent leaving group. In the second method, a direct conversion from the alcohol can be achieved by a transient species, usually an alkoxyphosphonium salt. 

HSAB is particularly useful for assessing the reactivity of ambident nucleophiles or electrophiles, and numerous examples of chemoselective reactions given throughout this book can be explained with the HSAB principle. Hard electrophiles, for example alkyl triflates, alkyl sulfates, trialkyloxonium salts, electron-poor car-benes, or the intermediate alkoxyphosphonium salts formed from alcohols during the Mitsunobu reaction, tend to alkylate ambident nucleophiles at the hardest atom. Amides, enolates, or phenolates, for example, will often be alkylated at oxygen by hard electrophiles whereas softer electrophiles, such as alkyl iodides or electron-poor alkenes, will preferentially attack amides at nitrogen and enolates at carbon. 

Macrolactonization can also be achieved by the Mitsunobu reaction [44] with inversion of the configuration of the alcohol. The reaction principle and mechanism are demonstrated in Scheme 24. Addition of triphenylphosphine to diethyl azodicarboxylate (DEAD, 73) forms a quaternary phosphonium salt 74, which is protonated by hydroxy acid 11, followed by phosphorus transfer from nitrogen to oxygen yielding the alkoxyphosphonium salt 76 and diethyl hydrazinedicarboxy-late 75. Then, an intramolecular Sn2 displacement of the important intermediate 76 results in the formation of the lactone 15 and triphenylphosphine oxide. 

The alkylation of phthalimide can also be accomplished with G-alkylisoureas and alkoxyphosphonium salts. Thus, the reaction of (9-alkyl-A(A -cyclohexylisourea with phthalimide aflbrded (V-alkylphthai-imides in 60-70% yields (DMF, 120 C, 2-24 h). Starting from (/ )-2-octyiisourea, (S)-2-octylamine was obtained in 97.6% ee, indicating 98% inversion of the configuration took place. ... 

The reactions involving alkoxyphosphonium salts are also efiective for the A(-alkylation of phthalimide with virtually complete inversion of the secondary methanol center. Thus, the reaction of (S)-alcohol (81) with phthalimide, DEAD and triphenylphosphine afforded (82), which was subjected to a sequence of reactions to yield (2/ ,5f )-diamine (83) and the (2/ ,5Sj-isomer in a ratio of 99.4 0.6. The secondary... 

Development of the chemistry of the salt (156) continues. When converted into the alkoxyphosphonium salts (157) and treated with, e.g., methyl-lithium or lithium dimethylcuprate, alkylation at the alkoxy carbon to form R—Me derivatives only occurs to a small extent, due to competition from the strongly nucleophilic N-methylanilide ion. However, alkylation (and arylation) at the alkoxy carbon has been achieved by the reaction of the salt (156) with mixed cuprates derived from an allylic alcohol, copper(i) iodide, and an organolithium reagent, enabling direct substitution of the hydroxy-group of allyl alcohols by alkyl or phenyl groups in a regio- and stereo-selective manner. ... 

Allyl alcohols can also be transformed into olefins by NaCNBH3-BF3 Et20, but some isomerizations can occur [SVl], The reduction of primary alcohols as well as allyl and benzyl alcohols into hydrocarbons by NaBH4 can be carried out via alkoxyphosphonium salts 2.34 generated in situ [HS6] (Figure 2.19). 

In view of the usefulness of alkoxyphosphonium salts in synthesis it is of interest to note that, depending on the mode of addition of the... 

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