Phosphonium salts with migration

The method of Kim et al.[89-93] starts from the synthesis of the three-carbon phosphonium salt according to the modified method of Corey et alJ94,95] The Wittig reaction of the phosphonium salt with a Z-protected a-amino aldehyde using potassium hexamethyldisilazanide provides the ds-alkene without racemization. Efficient hydrolysis of the orthoester without double bond migration is achieved by acidolytic hydrolysis with aqueous hydrochloric acid in tert-butyl alcohol under reflux conditions. Then, an a-amino acid methyl ester is coupled. The desired epoxide product is obtained by treatment with 3-chloroperoxybenzoic acid. The epoxidation reaction is stereoselective and predominantly provides one isomer (R,S S,R = 4-10 1). The trans-epoxide can also be prepared using a trans-alkene-containing peptide. A representative synthetic procedure to obtain the ds-epoxide isostere is detailed below. 

MisceUaneous.—The carbanions (94), formed from the reaction of the corresponding phosphonium salt with sodium ethoxide and the sodium salt of t-butyl hydroperoxide, decompose in a number of ways. Migration of a phenyl group to oxygen yields the phosphine oxide (95) and formation of the alkyl ethyl ethers may be due to the intermediacy of a carbene, which is trapped by solvent. ... 

The tungsten alkylidynes Tp W( = CH)(CO)2 and Tp W(=CPh)(CO)2 also arise from side reactions of phosphonium alkylidyne complexes with aryloxide nucleophiles from reaction of the quaternary phosphonium salts with adventitious hydroxide to give a dissociated alkyl anion or a product resulting from a 1,2-phenyl migration. At low temperature, phenyl migration is inhibited and only the terminal dissociation product is observed. At room temperature, both phenyl and C-H alkylidyne products form in an approximate 1 1 ratio. 

Treatment of (2-trimethylsUylphenyl-)methyl phosphonium salts with NaHMDS provided the corresponding ylide that underwent anionic 1,4-silyl migration to form the respective phenyl trimethylsUyl ylides that on reaction with methyl iodide gave phenyl-(l-trimethylsUylethyl)phosphonium iodides (Scheme 74). ... 

The migration of a C=C bond to form a C=N bond was also observed with hydro-xylamine [78, 79], hydrazine [80, 81] and primary amines [82]. The /f iminylphos-phine oxide formed in the reaction may serve as a Wittig reagent in the presence of a base to react with a ketone or an aldehyde leading to ,/fun saturated alkenyl-imines 153 (Scheme 10.74). The phosphorus group can be a phosphonium salt as well as a phosphonate. 

Schlosser670 proposed an equivalent mechanism at the phosphorane 64 stage, formed from the corresponding ylide and not from the phosphonium salt the driving force for the migration comes from the carbenoid nature of the carbon in the a-position to the phosphorus. This is consistent with the anionotropic nature of the migration. The mechanism is corroborated by a similar migration from the ylide 65670 (reaction 198). 

In 1989, a different approach was published by Orito [60], in which elaidinization ((Z) —> ( ) double bond isomerization) is used to obtain ( )-MNA from a (Z, )-mixture ofdiastereomers (Scheme 4.6). Gannet had observed that the iodine-induced photoisomerization of the methyl ester of MNA (48) gave only a 7 3 ( /Z) mixture [59], but Orito obtained a better diastereomeric ratio (8 1) using nitrous acid. Remarkably, no double-bond migration to form the more stable trisubstituted olefin was observed. This discovery paved the way to a very simple and general synthesis of the acidic component of capsaicinoids. Thus, a Wittig reaction of the phosphonium salt of a 6-bromohexanoic acid (49) with isobutyraldehyde (SO) afforded a 1 11... 

Phosphonium ylides carrying at least one proton at the a-carbon atom react with various electrophilic reagents with formation of a-substituted phosphonium salts or zwitterionic intermediates, from which a-substituted ylides are generated by deprotonation or proton migration, the former reaction being more important (equation... 

Many alkylidenephosphoranes can be transformed into new phosphonium ylides by reactions which take place in the side chain of a parent ylide, the a-C atom of the ylide group not being involved. Allylidenetriphenylphosphoranes react with a series of chloro compounds (alkyl chloioformates, acyl chlorides, 3-chloroacrylates, 2-chlorovinyl ketones, phosphorus chlorides) and other electrophilic compounds at the 7-C atom. Abstraction of a proton from the 7-position of the resulting phosphonium salts by a second mole of starting ylide (or proton migration) gives rise to the formation of -substituted derivatives of the original allylidenephosphoranes (equation 90). 

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