Butyllithium, reaction with phosphonium salts

All of the oxido ylide reactions demand the presence of at least one equivalent of lithium halide. This requirement is most easily satisfied when the starting alkylidenetriphenylphosphorane is generated by the conventional butyllithium method from phosphonium salts in THF. Thus, Maryanoff et al. (22a) treated Ph3P C4Hg Br" sequentially with butyllithium, benzaldehyde, butyllithium, and acid to give 60 (R = phenyl replace Me by propyl) con-... 

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 alkenes (hke 15-8) and in other ways. The phosphonium salts are most often converted to the ylids by treatment with a strong base such as butyllithium, sodium amide, sodium hydride, or a sodium alkoxide, though weaker bases can be used if... 

Complexes containing the ylide ligand can be also obtained by reaction of the yellow solution of ylides (prepared by addition of butyllithium to tetrahydrofurane or diethylether solutions of the phosphonium salt) with [AulCfiFs) (tht)]. The weak ligand tht is replaced and the ylide complex is obtained (Equation 3.5) [70]. 

The ylide obtained from (methyl)triphenylphosphonium bromide reacts with morpholine derivatives 597 to give phosphonium salts 598 which upon treatment with -butyllithium are converted to new ylides 599. In a reaction with aldehydes, ylides 599 form iV-(l,3-disubstituted allyl)-morpholines 602 (Scheme 94) <1996AQ138>. Another less common nucleophile that can be used for substitution of the benzotriazolyl moiety in Af-(a-aminoalkyl)benzotriazoles is an adduct of iV-benzylthiazolium salt to an aldehyde which reacts with compounds 597 to produce adducts 600. Under the reaction conditions, refluxing in acetonitrile, salts 600 decompose to liberate aminoketones 601 <1996H(42)273>. 

Bailey and coworkers were able to synthesize mono- and dilithiated phosphonioylides by the reaction of the phosphonium salt 15 with two or three equivalents of n-butyllithium. In both cases, the ylidic precursor 16 is generated by reaction with one equivalent of the base. By the addition of a further one or two equivalents of the base, the monolithiated compound 17 or the dilithiated compound 18 is formed, respectively (Scheme 6). The results were confirmed by NMR studies and trapping experiments. 

Fluonnated ylides have also been prepared in such a way that fluorine is incorporated at the carbon p to the carbamomc carbon Various fluoroalkyl iodides were heated with tnphenylphosphine in the absence of solvent to form the necessary phosphonium salts Direct deprotonation with butyllithium or lithium dusopropy-lamide did not lead to y hde formation, rather, deprotonation was accompanied by loss of fluonde ion However deprotonation with hydrated potassium carbonate in dioxane was successful and resulted in fluoroolefin yields of45-80% [59] (equation 54) p-Fluorinated ylides may also be prepared by the reaction of an isopropyli-denetnphenylphosphine yhde with a perfluoroalkanoyl anhydride The intermediate acyl phosphonium salt can undergo further reaction with methylene tnphenylphosphorane and phenyllithium to form a new ylide, which can then be used in a Wittig olefination procedure [60] (equation 55) or can react with a nucleophile [61] such as an acetylide to form a fluonnated enyne [62] (equation 56)... 

Carlson et al. obtained (Z)-9-tricosene 382 by reaction of nonanal 380 with the ylide generated from the phosphonium salt 381 and butyllithium in DMSO 219>220> (Scheme 68). Bestmann et al. 221> synthesized the (Z)-olefin 382 by olefination of tetra-decanal 384, with the ylide generated by treatment of the corresponding phosphonium salt 383 with potassium in HMPA 341 (Scheme 68). 

The reaction of trialkyl- and triaryl-phosphines with 1,3-benzodithiolylium salts leads to formation of phosphonium salts which are deprotonated by treatment with n-butyllithium to produce (69). The similar reaction of trialkyl phosphites in the presence of sodium iodide yields dialkyl phosphonates which can be deprotonated to (70). Both (69) and (70) can react further with ketones to give the 2-alkylidene-l,3-dithiole derivatives (71) (80AHC(27)151>. The ylide (72) has also been prepared (80H(l4)27l>. 

Phosphorus ylids are prepared by treatment of phosphonium salts with bases such as phenyllithium, butyllithium. dimsyl anion, or potassium f-butoxide. They are not isolated but used directly after preparation because they are sensitive to oxygen and moisture. The requisite phosphonium salts are available in great variety from the reaction of triphenylphosphine and primary or secondary alkyl halides, usually bromides [24]. 

TTF can also be prepared by the elimination of a proton and of triphenylphosphine in the final step. Thus, 1,3-dithiolylium salts (402) react with 2-triphenylphosphino-l,3-dithioles to afford intermediates which give TTF (403) upon treatment with base at low temperatures (Scheme 76). This method also permits the selective preparation of unsymmetrical TTF <78JOC369,82TLl8l3,83Mi 312-02). The phosphorus ylides used in these reactions are easily accessible by the reaction at — 78°C between -butyllithium and the corresponding phosphonium salt which is obtained by the reaction of triphenylphosphane with 1,3-dithiolylium salts <78JOC369>. 

Treatment of diphenylmethyltriphenylphosphonium bromide with butyllithium and elemental selenium followed by cyclopentadiene gave (67). The reaction could also be carried out with other substituted phosphonium salts <90H(3l)2i07,94JCS(Pi)2l5l>. 

The preparation and immediate reaction of alkyllithium for deprotonation of various acidic compoimds precisely illustrate this aspect (Fig. 34).i 8 representative reaction is the quantitative formation in a few minutes of 2-lithio-1,3-dithiane by sonication of f-butyl chloride, lithium, and 1,3-dithiane in THF. In situ generated butyllithium was used for the deprotonation of alkynes and phosphonium salts. With secondary amines, the strongly basic lithium amides are produced (p. 368). This procedure avoids the use of organolithium auxiliaries with solvent and temperature adjustments. o The isotopically labeled Li hexamethyl disilazide was obtained by this method.i i... 

Butyllithium is an unsuitable base on account of its sensitivity to air and moisture. In the process the phosphonium salt precursor (formed from the alcohol, Ph3P and hydrogen halide), together with aldehyde in methanol, are treated with methanolic sodium methoxide at — 30 C. After reaction the solution is neutralized with dilute sulphuric acid, the Vitamin A ester extracted into a hydrocarbon solvent and isolated after removal of solvent by distillation. 

Amino aldehydes can also be condensed with tiiphenylphosphonium ylids in a Wittig olefination reaction.134 Generation of the propargyl alcohol derivative 1.228 allowed conversion of the hydroxyl group to a bromide and then to the triphenyl-phosphonium salt. Treatment with n-butyllithium gave the ylid, which reacted with... 

The Ci5 phosphonium salt (10) was converted with n-butyllithium to the anionic form and then reacted with the epoxy ester (492) to give methyl 13,14-epoxyretinoate (493), which is unstable. In neutral methanol at room temperature, (493) had a half-life of 7 min, and underwent rearrangement to give the 14-hydroxy compound (30) (Davalian and Heathcock, 1979b). Compound (30) was also obtained from Cjg ketone (136) in a Darzens reaction. The spectral data of... 

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