Aldehydes with Wittig reagents

Reactions of Polvmer-Bound Aldehydes with Wittig Reagents... 

Reagents of type (57) react with simple aldehydes to give expected products, and with aj8-unsaturated ketones to give annelated compounds (Scheme 23).Half-protected a-diketones react with Wittig reagents at the unprotected ketone, and the second carbonyl group can then be deprotected. ... 

The aldehyde functionality present in 3-phenyl-2H-azirine-2-carbox-aldehyde reacts selectively with amines and with Qrignard and Wittig reagents to give a variety of substituted azirines. These azirines have been used, in turn, to prepare a wide assortment of heterocyclic rings such as oxazoles, imidazoles, pyrazoles, pyrroles, and benzazepins. ... 

Aldehydes can be prepared by the Wittig reaction using (methoxymethylene)-triphenylphosphorane as the Wittig reagent and then hydrolyzing the product with acid. For example,... 

Allyltin compounds can be prepared by simple modifications of the usual reaction involving allyl Grignard reagents (139), by the 1,4-addition of trialkyltin hydrides to 1,3-dienes 140,141), or by the reaction of an aldehyde or ketone with the appropriate, tin-carrying, Wittig reagents (142). 

The Wittig reagent (56) is best protected as an ester and reacts chemo-selectively with the aldehyde rather than the less reactive ketone in (57),... 

Piperazine linker 77 was treated with propargyltriphenylphosphine bromide to provide a resin-bound Wittig reagent (Scheme 40) [89]. Base treatment followed by aldehyde addition produced a resin-bound 2-amino-butadiene which was implemented in [4 + 2] cycloadditions. Alternatively, treatment with 3% TFA in CH2CI2 released a,(J-unsaturated methylke-tones in high yields. 

Methylenation of ol-(N-Boc-amino) aldehydes. Methylenation of these chiral aldehydes with the Wittig reagent or with CH2Ir-Zn-TiCl4 (13, 114) is accompanied by extensive racemization. However, the neutral reagent 1 obtained from CH2I2, Zn, and A1(CH3), converts these aldehydes to the protected allylamines in 40-75% yield and in >99% ee. 

E Selective Wittig reagents. The reaction of 1 with lithium in THF provides LiDBP, which on reaction with an alkyl halide (2 equiv.) and NaNH2 in THF gives a salt-free ylide such as 2 or 3, formed by reaction with ethyl iodide or butyl iodide, respectively. These ylides react readily with aldehydes at —78°, but the intermediate oxaphosphetanes are unusually stable and require temperatures of 70-110° for conversion to the phosphine oxide and the alkene, which is obtained in E/Z ratios of 6-124 1. Highest (E)-selectivity is observed with a-branched aldehydes. 

The Wittig reaction consists in the replacement of carbonyl oxygen of aldehydes and ketones by a methylene group with the aid of phosphine-methylenes resulting in the formation of cis or trans olefines. The reaction proceeds through the nucleophilic addition of Wittig reagent (phosphine methylene) across the > C = O bond and formation of an intermediate cyclic. 

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. 

Olefination of the Aldehyde 178 using a stabilized Wittig reagent followed by protecting group chemistry at the lower branch and reduction of the a,p-unsaturated ester afforded the allylic alcohol 179 (Scheme 29). The allylic alcohol 179 was then converted into an allylic chloride and the hydroxyl function at the lower branch was deprotected and subsequently oxidized to provide the corresponding aldehyde 161 [42]. The aldehyde 161 was treated with trimethylsilyl cyanide to afford the cyanohydrin that was transformed into the cyano acetal 180. The decisive intramolecular alkylation was realized by treatment of the cyano acetal 180 with sodium bis(trimethylsi-lyl)amide. Subsequent treatment of the alkylated cyano acetal 182 with acid (to 183) and base afforded the bicyclo[9.3.0]tetradecane 184. 

Scheme 5 shows a formal explanation of this conceptual idea for alkanes developed by Wilhams [60] the alcohol is first oxidized into the aldehyde affording a hydride complex. The aldehyde is then condensed with the Wittig reagent to form the unsaturated compound, which becomes hydrogenated by the hydride complex, thus regenerating the catalyst. 

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