Phosphine oxide ylide synthesis

Full details have appeared of the generation and use in synthesis of the chlorofluoromethylene-ylide (103). Fluoromethylenetriphenylphosphorane (104) has been prepared as shown and among other unusual ylides used in normal olelin synthesis are (105), (106), (107), (108), and (109). The latter gave acyclic phosphine oxides (110) in up to 50% yield. 

Reflecting similar developments throughout organic chemistry there has been a notable increase this year in the number of theoretical studies of ylides and their reactions. Methods of olefin synthesis involving phosphine oxides are discussed in Chapter 3. 

Review.1 This review covers use of phosphonium ylides, phosphoryl carbani-ons, and phosphine oxide carbanions in synthesis with particular emphasis on (Z)-and (E)-selectivities (558 references). 

The cyclohexanone (S3), an intermediate for the synthesis of thromboxane antagonists, has been prepared by a combination of phosphine oxide- and phosphonium ylide-based olefinations.30 Reaction of the lactone (50) with methoxymethyldiphenylphosphine oxide anion gave a poorly characterized adduct (presumably (51)) which on reduction with sodium borohydride, followed by treatment with sodium hydride gave the vinyl ether (52) in 80% overall yield from (SO) (Scheme 8). Further modification gave the required cyclohexanone (53). 

Phosphorus ylides are very important because of their use in the well-known Wittig reaction (1954) for the synthesis of alkenes. In the Wittig reaction, a phosphorus ylide (1) reacts with an aldehyde or ketone to yield the corresponding alkene (16) (Scheme 7). The reaction involves nucleophilic attack by the ylide (1) on the electrophilic carbonyl carbon atom to yield the betaine intermediate, which then collapses with elimination of the phosphine oxide and formation of the alkene (16). The driving force of the Wittig reaction is the production of the very strong phosphorus-oxygen double bond in the phosphine oxide (Scheme 7). 

The format of this chapter is similar to that used in previous volumes. The first section deals with methylene phosphoranes and their Wittig reactions, the second looks at the Horner-Wadsworth-Emmons reaction of phosphonate anions and the third the structure and reaction of lithiated phosphine oxides - an area which continues to receive particular attention. The majority of reports concerning ylides relate to their use in synthesis and in the final section some of these applications are reviewed. 

Chuang, S.-C., Lee, D.-D.. Santhosh, K.C., and Cheng, C.-H., Fullerene derivatives bearing aphosphite ylide, phosphonate. phosphine oxide, and phosphonic acid. Synthesis and reactivities, 7. Org. Chem., 64, 8868, 1999. 

Japanese female peach fruit moth have been synthesised (Scheme 10).2 9 The phosphine oxide starting material (51) was obtained from a Wittig reaction of the ylide derived from 1,1-diphenylphospholanium perchlorate. The reaction of (l-methyl-2-propenyl)diphenylphosphine oxide carbanion (55) with the optically active aldehyde (54) is the key step in a short synthesis of the sesquiterpenes (-)-a-selinene (58) and (-t-)-a-helmiscapene... 

Phosphorus-based olefinations continue to be the most widely used methods for the synthesis of alkenes. An understanding of most facets of the mechanism of the Wittig reaction seems to have been achieved and this has been summarised in a substantive review. Some of the principles established in these mechanistic studies can be applied to phosphorus-based olefinations other than the Wittig reaction. However, substantive mechanistic studies of phosphine oxide-based and phosphonate-based oiefinations are urgently required. A combination of the variety of phosphorus-based methods and the improved understanding of their mechanisms now aliows a substantiai degree of controi of both reactivity and stereochemistry in olefin synthesis. However, studies are required of the applications of established structure-reactivity relationships in ylides and of the various carbon and nitrogen ylide-anions recently reported. 

In volume 29 this chapter will, for the first time since volume 11, have a new author. Much of the ylide chemistry discussed in volume 11 would not be out of place in the current volume. In volume 28 an even wider application in synthesis, helped by improvements in available bases and other reagents and conditions, is apparent. A better understanding of mechanism, particularly of olefin synthesis, is available and this has enabled improved control of stereochemistry in all its forms, although improved stereo-control has also derived from a greater use of phosphonate and phosphine oxide anions. However, the opportunities offered by the enormous improvements in spectroscopic techniques, particularly NMR and mass spectrometry, and chiral and preparative HPLC and the increased demands of modem biology and medicine have perhaps had the greatest influence. 

Overall levels of innovation this year in the area of ylide chemistry are disappointingly low. All the various forms of phosphorus-based olefination continue to be used widely in synthesis and perhaps the relative paucity of new phosphorus chemistry is a reflection on the extent to which these methods have been developed. One area which does continue to expand, and where there is still considerable potential, is the use of phosphorus-stabilised anions in anantioselec-tive and asymmetric synthesis. Warren s continuing use of phosphine oxides and Denmark s excellent contributions to this area are especially worthy of mention. 

The Wittig reaction involves the interaction of an aldehyde or ketone with a phosphorus-containing carbanionic species, in which the phosphorus is bonded directly to the carbanionic site. At the time of discovery of the reaction, that specification described the triphenylphosphonium alkylides 343 later developments employed the anions from tert-phosphine oxides, the use of which has been described elsewhere in this series and also from a wide variety of phosphonic and phosphinic esters. This latter application will be considered more fully in Chapter 6. An early application of the reaction to the synthesis of alkenephosphonic acids, and which involved an ylide, employed the stable compound 344, generated from 345 by the action of a strong base. Reactions between 344 and aliphatic or aromatic aldehydes at 100 °C in toluene or dmso gave the diphenyl esters of (alk-1-enyl)phosphonic acids or (2-arylethenyl)phosphonic acids. ... 

In the reaction of nitroxyl with tertiary phosphines the corresponding aza-ylide was formed along with the phosphine oxide as the by-product (HNO + 2R3P R3P = NH + R3P = O). " A novel synthesis of pyrroles involves the reaction of a,p-unsaturated imines and acid chlorides. The cyclization is mediated by triphenylphosphine that is converted to the P-oxide during the reaction. In the reaction of phosphonoallenes with 2-iodophenol in the presence of Pd(OAc)2/PPh3, in addition of the expected benzofurans, the oxidized derivative of triphenylphosphine oxide (2-hydroxyphenyl-diphenylphosphine oxide) was also formed as a minor by-product. ... 

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