The Wittig Reaction in Industrial Practice

The effects of a scientific discovery on industrial practice are illustrated with reference to the Wittig reaction. The aim of utilizing the Wittig reaction of linking terpenoid building blocks to give vitamin A and carotenoids on an industrial scale prompted extensive research and development work of a synthetic and chemical engineering nature. The importance of the Wittig reaction and its variants in the synthesis of active compounds and fine chemicals in industrial research is demonstrated in the present article.     

Rasta Resin–PPh3–NBniPr2 and its Use in One‐Pot Wittig Reaction Cascades

A new triarylphosphine–tertiary amine bifunctional polymeric reagent has been prepared and used effectively in a variety of one‐pot Wittig reactions. The design of this reagent resolved a deficiency of a previously reported related material, and allowed it to perform more efficiently in such reactions. Furthermore, it was readily recyclable, and was also successfully applied in cascade processes involving one‐pot Wittig reactions followed by either a conjugate reduction or a reductive aldol reaction. In these reaction cascades, the phosphine oxide groups generated in the Wittig reaction served as the catalyst for the subsequent reaction.     

Total synthesis of leustroducsin B

Leustroducsin B was synthesized via a convergent route based on division of the leustroducsin molecule into three segments A, B, and C. Two coupling reactions (Julia coupling reaction and Nozaki-Hiyama-Kishi (NHK) reaction) were employed for coupling of segments A and B: segment A1 for the Julia coupling reaction was prepared by a combination of Sharpless asymmetric epoxidation and an epoxide-cleavage reaction with an organoaluminum reagent, while segment A2 for the NHK reaction was synthesized from optically active alcohol that had previously been prepared by lipase-catalyzed kinetic resolution. Segment B, whose structure was modified with some functional groups, was synthesized from (R)-malic acid by a combination of Wittig reaction and Sharpless asymmetric dihydroxylation, and segment C, containing a cyclohexane moiety, was prepared by asymmetric Diels-Alder reaction. Segment B was first coupled with segment A1 via the Julia coupling reaction, but the yield was low due to unexpected epimerization. The NHK reaction of segment A2 proceeded to give the coupling product in good yield. This product was coupled with segment C via Wittig and Stille coupling reactions, and finally, phosphorylation was carried out by partial hydrolysis of a cyclic phosphate to give leustroducsin B.     

Some rearrangements initiated by methylene triphenylphosphorane

Treatment of 17α-acetyl-Δ⁴-estren-17β-ol with methylene triphenylphosphorane initiates a d-homo rearrangement followed by the intended Wittig reaction. This rearrangement can be explained by the proton abstracting properties of the applied Wittig reagent. These properties are also responsible for the rearrangements observed when using 17α-acetyl-Δ⁴-estren-17β-ol 17-acetate as a substrate. They lead to an intramolecular condensation of the acetyl- and acetoxy-side-chain. Subsequent reactions depend on the conditions used.     

A convergent approach for the total synthesis of (−)-synrotolide diacetate

A simple carbohydrate based convergent approach towards the total synthesis of (−)-synrotolide diacetate is described employing a Sharpless asymmetric epoxidation, a Grignard assisted lactol opening with a terminal alkyne and a Wittig reaction using the Horner-Emmons reagent as the key steps.     

保幼激素类似物11-甲氧基-3,7,11-三甲基-2,4-十二碳二烯酸异丙酯的简便全合成

从价廉的丙酮出发,首先经羟醛缩合、脱水、氧化、酯化、溴代反应合成了4-溴-3-甲基-2-丁烯酸异丙酯,继而与亚磷酸三乙酯反应得到了Wittig-Homer试剂,随后与香茅醛发生Wittig-Horner反应,最后在阳离子树脂催化作用下与甲醇醚化,成功地全合成了具有保幼激素活性的昆虫生长调节剂11-甲氧基-3,7,11-三甲基-2,4-十二碳二烯酸异丙酯.所得标题化合物的四种异构体中,具有较高生物活性的(2E,4E)-异构体的含量达66%.各步所合成化合物的结构经1H NMR,IR,MS分析确证.     

Synthesis of nitrogen heterocycles by condensation of the conjugate base of open-chain reissert compound analogs with vinyltriphenylphosphonium bromide (schweizer's salt)

Reaction of the conjugate base of several open-chain Reissert compound analogs with vinyltriphenylphosphonium bromide is shown to afford a convenient route to substituted pyrroles. The condensation is a two-step process involving an initial reversible addition to form an unstabilized Wittig reagent followed by an intramolecular Wittig reaction upon the carbonyl group of the tertiary amide functionality with concomitant elimination of HCN. Several applications to the synthesis of 1,2,5-trisubstituted pyrroles are presented, together with attempts to expand this methodology to the synthesis of other heterocyclic systems.     

Chloroethoxy(trimethyl)silane: A hard-base trap which preserves tms ether groups and improves the wittig methylenation of gibberellins

A reagent, 2-chloroethoxy(trimethyl)silane (CETS), has been devised which ensures the preservation of TMS ether groups during Wittig methylenation in protic media and which makes this formerly capricious reaction with 16-keto gibberellins a reliable and straightforward procedure.     

具有叶绿素-a碳架的苯乙烯基取代Z/E-二氢卟吩衍生物的合成

The Wittig reaction of methyl pyropheophorbide-d 2,obtained from methyl pyropheophorbide-a 1,with ben-zyltriphenylphosphonium bromide was performed to yield isomers 3a and 3b.The Vilsmeier reaction of nickelcomplex 4 or 7 with 3-dimethylaminoacrolein in the presence of phosphoryl chloride was carried out to form20-meso-2'-formylvinylpyropheophorbide-a 5 or 8,which was reacted with Wittig reagent to afford nickel complexisomers 6a and 6b or 9a and 9b,10a and 10b.     

Electrografting: a powerful method for surface modification

Electrografting refers to the electrochemical reaction that permits organic layers to be attached to solid conducting substrates. This definition can be extended to reactions involving an electron transfer between the substrate to be modified and the reagent, but also to examples where a reducing or oxidizing reagent is added to produce the reactive species. These methods are interesting as they provide a real bond between the surface and the organic layer. Electrografting applies to a variety of substrates including carbon, metals and their oxides, but also dielectrics such as polymers. Since the 1980s several methods have been developed, either by reduction or oxidation, and some of them have reached an industrial stage. This critical review describes the methods that are used for electrografting, their mechanism, the formation and growth of the layers as well as their applications (742 references).     

Synthesis of β,β′‐Porphyrin Dimer Linked by Vinylene

Synthesis of a novel β,β′‐tetraalkylporphyrin dimer linked by vinylene was discribed, in which the dimer was readily prepared from a porphyrin‐derived Wittig reagent and a mono‐formylated porphyrin via Wittig reaction. No π‐conjugation between the two porphyrin rings was obserbed, and the dimer was in trans form.     

A one-pot silyl-Reformatsky olefination

A novel one-pot olefination reaction has been developed, involving the stereoselective formation of (E)-α,β-unsaturated esters/ketones from the reaction of α-bromocarbonyl compounds with aromatic aldehydes. The reactions use a reagent combination of trichlorosilane, and triethylamine and may proceed via the in situ formation of a trichlorosilyl ketene acetal. The general procedure offers key advantages (high conversions, low quantities of organic soluble by-products) over the conventional Wittig reaction.     

Oxidative Cleavage of Oximes with Silica‐Gel‐Supported Chromic Acid in Nonaqueous Media

A simple procedure for a clean and high‐yielding oxidative deoximation of benzaldoximes and ketoximes using a silica‐gel‐supported chromic acid reagent has been developed. This solid‐supported reagent allows us to carry out this reaction in nonaqueous dichloromethane reaction media.     

Total synthesis of an antitumor antibiotic,Fostriecin (CI-920)

The total synthesis of an antitumor antibiotic, fostriecin (CI-920), via a highly convergent route is described. A characteristic feature of the present total synthesis is that the synthesis was achieved via a coupling procedure of three segments A, B, and C. The unsaturated lactone moiety of fostriecin, corresponding to segment A, was constructed from a known Horner-Emmons reagent, and the stereochemistry of the C-5 position was introduced by asymmetric reduction with (R)-BINAl-H. Segment B having a series of stereogenic centers was synthesized from (R)-malic acid and the stereogenic centers at the C-8 and C-9 positions were prepared by a combination of Wittig reaction and Sharpless asymmetric dihydroxylation reaction. The conjugated Z,Z,E-triene moiety of fostriecin, corresponding to segment C, was eventually constructed by Wittig reaction and Stille coupling reaction. The phosphate moiety, which is known to be essentially important for the antitumor activity, was introduced via two routes: (i) direct phosphorylation of the monohydroxyl derivative in which other hydroxyl groups are protected with silyl groups; (ii) cyclic phosphorylation and selective cleavage of the cyclic phosphate derivative. Although the former route is basically the same as those reported by other groups, the latter route is novel and more effective than the former one. The present total synthesis would serve as a versatile synthetic route to not only fostriecin, but also its various analogues including stereoisomers.     

Studies on ferrocene derivatives XIX. The acylation of [m]-ferrocenophanes and 1,1′-diethylferrocene and the direct conversion of the acylferrocenes to ethers and alkenes

The Vilsmeir formylation of 1,1′-diethylferrocene, [3]- and [4]ferrocenophane has been shown to produce mainly, but not exclusively, the β-isomer and the ratio of β/α for the acetylation of [3]-ferrocenophane depends on the reagent used in the reaction. These aldehydes are directly converted to ethers by reduction with sodium borohydride in alcohol and also to alkenes via the Wittig reaction.     

Synthesis of some furo‐thiazolidine derivatives starting from aldimines

Alkyl and aryl substituted furothiazolidine derivatives have been synthesized by the reaction of Wittig reagent with benzylidene derivatives of 4‐thiazolidinones obtained from aldimines and thioglicolic acid.     

Wittig homologation of 2-(chloromethyl)-2H-chromen-2-ol derivatives: a new facile synthesis of substituted 2,3-dihydrobenzoxepine-4-carboxylates

Wittig homologation of 2-(chloromethyl)-2H-chromen-2-ol derivatives 2a–t with (ethoxycarbonylmethylene)triphenylphosphorane provided the 2-oxoethylidene-2,3-dihydrobenzoxepine-4-carboxy-lates 3a–t with Z (cis) selectivity. Various basic catalysts were studied for the reaction of 2-(chloromethyl)-2H-chromen-2-ol 2a with the combination of Wittig reagent to provide compound 3b. The reaction of 2-(chloromethyl)-2H-chromen-2-ol 2a with other Wittig reagents, such as methylene(triphenylene)phosphorane and (1-ethoxycarbonylethylidene)triphenylphosphorane provided ketone derivative 4a rather 2-oxoethylidene derivative 3b. The ketone derivative 4a was reacted with Wittig reagent (ethoxycarbonylmethylene)triphenylphosphorane to give 2,3-dihydrobenzoxepine-4-carboxylate 3b. The present approach is novel, straight forward and being reported for the first time.     

An alternative Route to (±)-Warburganal Synthon

The transformation of the ketone (1) to the unsaturated diester (11) a potential intermediate for the warburganal (12) is described. The Wittig reaction of theketone (1) with methylenetriphenylphosphorane afforded the olefin (2) which reacts with Woodward's reagent (MeCOOAg, I₂ and MeCOOH and H₂O) to give the diol (13). This on heating with dimethylsulfoxide afforded the tetralin (14)     

Stereoselective Synthesis of Unsaturated and Functionalized l-NHBoc Amino Acids, Using Wittig Reaction under Mild Phase-Transfer Conditions

The stereoselective synthesis of a new amino acid phosphonium salt was described by quaternization of melting triphenylphosphine with the γ-iodo NHBoc-amino ester, derived from l-aspartic acid. The deprotection of the carboxylic acid function to afford the phosphonium salt with a free carboxylic acid group was achieved by a palladium-catalyzed desallylation reaction. This phosphonium salt was used in the Wittig reaction with aromatic or aliphatic aldehydes and trifluoroacetophenone, under solid-liquid phase-transfer conditions in chlorobenzene and in the presence of K(3)PO(4) as weak base, to afford the corresponding unsaturated amino acids without racemization. Thus, the reaction with substituted aldehydes allows to graft various functionalized groups on the lateral chain of the amino acid, such as trifluoromethyl, cyano, nitro, ferrocenyl, boronato, or azido. In addition, the reaction of the amino acid Wittig reagent with α,β-unsaturated aldehydes leads to amino acids bearing a diene on the lateral chain. Finally, this amino acid phosphonium salt appears to be a new powerful tool for the preparation of unsaturated and non-proteinogenic α-amino acids, directly usable for the synthesis of customized peptides.     

卡宾的钨配合物与二氯甲基Wittig试剂的反应

卡宾的过渡金属配合物是一个十分活跃的研究领域,有关它们的制备方法及性质的研究工作正日益引起人们的注意。Burkhardt等发现,卡宾的钨配合物能与Witting试剂反应,生成烷氧基取代烯烃。本文将卡宾的钨配合物进一步用于与二氯甲基Wittig试剂的反应,合成1,1-二氯-2-烷氧基烯烃。众所周知,1,1-二卤代烯烃是一类产生不饱和卡宾的前体化合物。因此,通过对卡宾的钨配合物与二氯代Wittig试剂之间的反应研究,还可以为进一步研究烷氧基取代不饱和卡宾的性质提供方便。