Lithium salts, Wittig reaction

The thermolabile, unsubstituted 3-benzothiepin (3) can be synthesized by a double Wittig reaction, in analogy to the Knoevenagel condensation (vide supra). This is achieved by condensation of phthalaldehyde with the bis(triphenylphosphonium) salt of bis(bromomethyl) sulfide in the presence of lithium methoxide as base at — 30"C.68... 

Betaine precipitates have been isolated in certain Wittig reactions, but these are betaine-lithium halide adducts, and might just as well have been formed from the oxaphosphetane as from a true betaine. However, there is one report of an observed betaine lithium salt during the course of a Wittig reaction. In contrast, there is much evidence for the presence of the oxaphosphetane intermediates, at least... 

It should be noted here that the lithium salt of hexamethyldisilazane li-HMDS 492 (and Na-HMDS-(486) and K-HMDS in Sections 5.1.2 and 5.1.3), which is readily obtained on treatment of a solution of HMDS 2 in hexane or THF with butyUithium at -78 °C, is not only a very useful and selective strong base, e.g. for Wittig reactions, but can also add to carbonyl groups to yield the silylated Schiff bases or nitriles (cf. Sections 4.7 and 5.1.3) or to nitriles to afford N-silylated ami-dines. Alkylation of the Li-HMDS 492, e.g. with allyl bromide, affords, furthermore, N,N-bis(trimethylsilylated) primary amines such as 43 [64]. The combina-... 

This accounts for the considerable discrepancy between the alkene Z/E ratio found on work-up and the initial oxaphosphetan ais/trans ratio. By approaching the problem from the starting point of the diastereomeric phosphonium salts (19) and (20), deprotonation studies and crossover experiments showed that the retro-Wittig reaction was only detectable with the erythreo isomer (19) via the cis-oxaphosphetan (17). Furthermore, it was shown that under lithium-salt-free conditions, mixtures of (19) and (20) exhibited stereochemical drift because of a synergistic effect (of undefined mechanism) between the oxaphosphetans (17) and (18) during their decomposition to alkenes. 

Oxidative coupling55 of the acetylenic alcohol 146 under Eglinton conditions followed by acidic treatment of the product gave the aldehydes 147 (37%) and 148 (8%). Wittig reaction of aldehyde 147 and the bisphosphonium salt 120 with 1,5-diazabicyclo[4.3.0]non-5-ene as base gave the [21]annulenone 149. This on reduction with lithium aluminium hydride-aluminium chloride gave the homoannulene... 

Organometallic betaines of type I can be considered as the closest structural analogs of carbon betaines of the (+ )P-C-C-X( ) type (IV), which were regarded for a long time as possible intermediates in classical reactions of carbonyl and thiocarbonyl compounds with phosphorus ylides (Wittig and Corey-Chaykovsky reactions and related processes,5,6 Scheme 1). Vedejs and coworkers7,8 proved unambiguously that oxapho-sphetanes (III) are true intermediates in the reactions of nonstabilized phosphorus ylides with carbonyl compounds. The formation of oxabetaines (+)p-c-c-o(-> was detected only in the form of their adducts with lithium salts.9,10... 

The stereochemical outcome of the Wittig reaction can depend on the presence or absence of lithium salts. This may be due to a betaine intermediate stabilized by lithium cation. A stable adduct of this type has now been observed during a Wittig reaction. When Ph3P=CH2 is treated with 2,2 -dipyridyl ketone, P NMR shows the formation of an oxaphosphetane (72) and addition of lithium bromide gives the chelation-stabilized betaine lithium adduct (73). 

Phosphorus ylides have been reviewed and an intermediate betaine lithium salt adduct (stabilized by complexation with lithium ions and by the chelating effect of pyridyl ligands) has been observed spectroscopically for the first time during the course of a Wittig reaction. ... 

Spectroscopic evidence for formation of a betaine lithium salt adduct during the course of a Wittig reaction has been reported for the first time. The ylide Ph3P=CH2 formed oxaphosphetane (71) on treatment with 2,2 -dipyridyl ketone at -60 °C in... 

The Wittig reaction of lithium a-(dimethylamino)-alkoxydes and a C15 alkyltriphenylphosphonium salt was used by Wang et al. to elaborate the ethylenic linkage of retinol [79]. This in situ method offers the unique advantage in its application to labile aldehydes, which otherwise would become isomerised or self-condensed, Fig. (44). 

The overall sequence of three steps may be called the Wittig reaction, or only the final step. Phosphonium salts are also prepared by addition of phosphines to Michael olefins (like 5-7) and in other ways. The phosphonium salts are most often converted to the ylides by treatment with a strong base such as butyllithium, sodium amide,640 sodium hydride, or a sodium alkoxide, though weaker bases can be used if the salt is acidic enough. For (PhjP CHj, sodium carbonate is a strong enough base.641 When the base used does not contain lithium, the ylide is said to be prepared under "salt-free conditions.642... 

Wittig and co-workers2 have shown that triphenylborane can be readily synthesized in high yield by simple thermal decomposition of trimethylammonium tetraphenylborate. They obtained the latter compound by collecting the precipitate which was formed on mixing aqueous solutions of trimethylammonium chloride and lithium tetraphenylborate. The lithium salt was isolated from the products of the reaction of boron trifluoride-etherate with... 

Alternatively it is possible to have both steps, addition and elimination, occur spontaneously if appropriate reagents are employed. There are two common strategies in use the Wittig reaction and the Wittig-Horner reaction. The Wittig olefination uses a phosphorus-stabilized carbanion (ylid) as a nucleophile and a carbonyl compound as an electrophile. Typically the ylid is generated in situ from a triphenylphosphonium salt and a strong base such as LDA or an alkyl lithium. 

Acyl silanes can display disparate behaviour when treated with carbon nucleophiles, even of related types5,61149. For example, when aroyl silanes were treated with a Wittig reagent, none of the expected alkenes was obtained, and the only reaction products isolated were silyl enol ether and triphenylphosphine (Scheme 73)182,183. When alkanoyl silanes were treated with Wittig reagents, however, only the normal olefinated vinyl silane products were isolated (Scheme 74)182-184 Under soluble lithium salt conditions, Z-vinyl silanes were produced with very high selectivities the reaction was used to prepare a pheromone component (50) of the sweet potato leaf folder moth (Scheme 75)183. 

The Schlosser Modification of the Wittig Reaction allows the selective formation of -alkenes through the use of excess lithium salts during the addition step of the ylide and subsequent deprotonation/protonation steps. 

Addition of the ylide to the carbonyl is postulated to lead first to the zwitterionic intermediate betaine, which would then close to form a four-membered cyclic intermediate, an oxaphosphetane. The existence of the betaine hasn t been fully established, although its intermediacy plays an important role in the Schlosser Modification. Betaines may be stabilized by lithium salts leading to side products therefore, suitable bases in the Wittig Reaction are for example NaH, NaOMe, NEt3). 

A mechanistic interpretation of the Wittig reaction, allowing the various experimental data collected during many years to bring into accord with theoretical demands, was reported only 25 years after its discovery4,7 9). Wittig already formulated a zwitterionic adduct of the form of a P—O-betain 52) (Scheme 2). This is better described by formula 6, since at that time almost exclusively lithium alkyls have been used for the deprotonation of the phosphonium salts. The reversibilitiy of the... 

For the preparation of the second component 421 of the cockroach pheromone Burgsthaler et al. 228) also used a Wittig reaction. Lithium acetylide is alkylated with the two halides 414 and 416 and the resulting alkynyl bromide 417 converted into the phosphonium salt. Olefination of the corresponding ylide with 9-bromo-2-nonanone 418 gives a (Z)/( )-mixture of olefin 419 which is converted into the pheromone 3,ll-dimethyl-29-hydroxynonacosan-2-one 421 by aeetoaeetate synthesis, hydrogenation, hydrolysis, and decarboxylation 228) (Scheme 73). 

Schlosser modification of Wittig reaction The presence of soluble metal salts such as lithium salts decreases the aVfrans-selectivity. The normal Wittig reaction of non-stabilized ylides with aldehydes gives Z-alkenes. The Schlosser modification of the Wittig reaction of non-stabilized ylides furnishes -alkenes. In the presence of lithium halides oxaphosphetanes can often be observed, but betaine-lithium halide adducts are also formed. If lithium salts are added to the equilibrium, oxaphosphetane formation and elimination of... 

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