Aldehydes with phosphoranes

Barluenga et al. prepared the desired ami-nodienes by Wittig olefination of aldehydes with phosphoranes generated in situ from / -enamino phosphonium salts. [31] The procedure was extended by Enders et al. to chiral products by introducing (S,S)-dimethylmor-pholine as a novel C2-symmetric chiral auxiliary as shown in Scheme 4 (reactions Scheme 4, 11 to 14). [32]... 

E,Z)-l -Dienes.1 This unit, often present in insect pheromones, can be obtained with high stereoselectivity by reaction of an aldehyde with 1 to provide an (E)-a,p-enal (2), which on reaction with a phosphorane generated with BuLi and HMPT provides (E,Z)-dienes almost exclusively. 

Z)-Allyltrimethylsilanes.1 Reaction of aldehydes with 2-trimethylsilylethy-lidinetriphenylphosphorane has been used to convert aldehydes into allyltrime-thylsilanes as a mixture of (E)- and (Z)-isomers (9,492). Replacement of triphen-ylphosphine by tris(2-methylphenyl)phosphine enhances (Z)-selectivity, particularly in reactions with aliphatic saturated aldehydes. These aldehydes can be converted into the (Z)-allylsilanes (Z/E > 94%) with 1, and with use of BuLi at 0° for generation of the phosphorane. 

Mori also succeeded in synthesizing the optically active ipsdienol 350 via carbonyl olefination of the acetonide 345 of (RX+)-glycerine aldehyde with isopropylidene-phosphorane to form 346. Methoxymercuration of346 followed by the splitting of the protective group, tosylation and treatment with alkali afford the epoxide 349 which is converted into the optically active (R)-350 via the same reaction sequence as in the synthesis of 344 according to Scheme 61 2101 (Scheme 62). 

One of the reported syntheses of ( )-9-oxodec-2-enoic acid 392, the queen substance of the honey bee Apis mellifera, uses two ylide reactions 222). Starting from pimelic acid 385 the resonance-stabilized ylide 386 is prepared by alkylation of methylene-triphenylphosphorane 209 and the former hydrolyzed to 7-oxooctanoic acid 387. Reduction of the corresponding thiol ester 389 and olefination of the resulting aldehyde 390 with phosphorane 67 gives the ( )-2-unsaturated ester 391. The latter was hydrolyzed to pheromone 392 222) (Scheme 69). 

Although the reaction of aldehydes with /9-earbonylmethylene phosphoranes constitutes a good synthetic route to a,/5-unsaturated carbonyl compounds,11-14 this procedure is normally not applicable to ketones. This limitation has recently been overcome by the reaction of ketones with the cyclo-hexylimine derivative of / -earbonylmethylenephosphonates.15... 

Reagents of type 251 (Fig. 94) are aldehydes or phosphoranes which, by reaction with kctonic and indolic Mannich bases, allow the production of p-diketones 252 or phosphoranes 253, respectively. In the former case, the conversion of aldehyde to ketone is thus made possible, - - and in the latter, the formation of unsaturated derivatives by subsequent reaction of the PPh3 residue with carbonyl compounds is allowed. - ... 

Wittig reactions of a-alkoxy aldehydes and sugar lactols, such as pentose ketal (48), with stabilised ylides usually proceed with low ( )-selectivity. However, Harcken and Martin have discovered that treatment of these aldehydes with (methoxycarbonylmethylene)tributyl phosphorane (49) and a catalytic quantity of benzoic acid produces the heptenonate (50) with a E Z ratio of 95 5. The stereoselectivity of the reactions between aldehydes and spirophosphoranes (51) has been examined and the phosphoranes found to favour the formation of (Z)-a,p-unsaturated aldehydes and amides. ... 

Derrick, A.M., and Thomson, N.M., Preparation of itaconates and succinates via olefination of aldehydes with succinate phosphonates or phosphoranes followed by optional asymmetric reduction, Pfizer, Eur. Patent Appl. EP 1199301, 2002 Chem. Abstr., 136, 325323, 2002. 

Further steps in the synthesis of coumarin via the ortho-hydroxy benzaldehydes involve a Perkin reaction. Here, in the first instance, a cinnamic acid is obtained. The cinnamic acids are obtained more conveniently by the Wittig reaction of the aldehydes with the stable phosphoranes, Ph3P=C—COOEt. Indeed lithiation... 

Synthesis from o-mannose A total synthesis of D-(- -)-biotin (1) from D-mannose has also been reported (Scheme Treatment of 2,3 5,6-di-0-isopropylidene-a-D-mannofuranose (17) with benzoyl chloride followed by selective hydrolysis of the terminal acetal group afforded 1-0-benzoyl-2,3-0-isopropylidene-a-D-mannofuranose (18). Subsequent periodate oxidation and chain extension with the proper phosphorane followed by hydrogenation gave the uronate derivative 19. Treatment of 19 with NaOCHs followed by reduction of the resulting aldehyde with sodium borohydride afforded compound 20. 

Oxidation of 754 under Swem conditions provides aldehyde 760. Wittig reaction of 760 with phosphoranes yield Z-olefins 761 [166] phosphonates yield the. E-olefin 762 (Scheme 110) [102]. Reduction of 762 in acetic anhydride gives N-acetyl-protected diol 763, which is identical to one of the degradation products of the polyene macrolide lienomycin. 

This conclusion is in agreement with a remark of Lewis who stated that slower reacting systems tend to show a greater effect under microwave radiation than faster reacting ones [82]. In this way, during solvent-free Wittig olefination with phosphoranes, it was shown that the benefit of MW irradiation increases with less reactive systems. The best stabilized phosphoranes do not react at all in the solid state with aldehydes or ketones under conventional heating but necessitate MW irradiation [83]. 

In spite of its wide use, there are still three major problems with the Wittig reaction. 1) The stereochemistry often cannot be controlled. 2) Ketones and hindered aldehydes fail to react with phosphoranes that are hindered or are stabilized by strongly electron withdrawing substituents. 3) The by-product triphenylphosphine oxide can be difficult to separate from the product alkene. Often the alkene and the triphenylphosphine oxide cannot be separated by extraction, distillation, or crystallization, and column chromatography is required. 

For the synthesis of some symmetrical carotenoids, p,p-carotene (3), another strategy based on the dimerization of a C2o-intermediate (2 x C20 = C40), has been used [7-9]. Since the yields of such coupling reactions via the corresponding phosphoranes, sulphones or aldehydes with Ti as a reagent) have not been very high, this approach is only efficient if the C2o-building blocks, like, for example vitamin A, are readily available and inexpensive (Scheme 5). 

The sulfone-alkylation method of Julia (1968) was a significant advance in retinoid total synthesis and has potential utility for labeled s)mthesis work. But the most useful reactions that have been adapted for the preparation of labeled retinoids are the well-developed procedures for the Wittig (Pommer, 1960) and the Homer-Emmons reactions (Bautagy and Thomas, 1974). These reactions are for synthesis of unsaturated and trans- and cw-a,p-enone compounds from the condensation of aldehydes and ketones with phosphoranes and with phos-phonoacetates, phosphonoacetonitrile, and oxophosphonates. These reactions suggest profitable application to the synthesis of retinoids, including labeled materials. 

A basically different approach to sialic acid synthesis was recently described by Mirzayanova et al. (1970) (Figure 13). N-Acetyl-o-manno-samine was subjected to the cyanohydrin reaction, the cyano group converted to an aldehyde, and the latter condensed with phosphorane XLVII via the Wittig reaction. Mild hydrolysis gave a crystalline product that was identical to natural NANA in elemental analysis, optical rotation, melting point, chromatographic behavior, and color reactions. 

Olefin synthesis Irom phosphorane ylides (e g 3) with aldehydes or ketones cis olelins predominate in aliphatic systems trans m coniugated olefins... 

The reaction of an alkylidene phosphorane 1 (i.e. a phosphorus ylide) with an aldehyde or ketone 2 to yield an alkene 3 (i.e. an olefin) and a phosphine oxide 4, is called the Wittig reaction or Wittig olefination reaction. ... 

Another example of this preference is found in the enantiospecific syntheses of tritium-labeled leukotrienes(/i). Commercially available 3-nonyn-l-ol was converted to its phosphorane (16) and Wittig-coupled with the unsaturated aldehyde (17) to afford 18, which was reduced over Lindlar catalyst to give 19. 

Phenylcyclopent[c]azcpine (33a) and 6,7-fused cyclopentazepines 33b-d are formed in moderate yields in a one-pot, two-stage process involving initial condensation of triphenyl-[(l-phenylvinyl)imino]phosphoranes 32 with 6-(dimethylamino)fulvene-2-carbaldehyde (30), followed by an intramolecular aza-Wittig reaction of the iminophosphorane with the pendant aldehyde function.5 The method fails with the unsubstituted vinylphosphorane 32 (R1 = R2 = H). 

Trimethylstannyl)ethylidene]phosphoranes have been generated by conjugate addition of trimethylstannyllithium to triphenylvinylphosphonium bromide30 and, more efficiently, by deprotonation of the corresponding / -(trimethylstannyl)phosphonium salt31, and condensed with aldehydes and ketones. 

In the Wittig reaction an aldehyde or ketone is treated with a phosphorus ylid (also called a phosphorane) to give an alkene. Phosphorus ylids are usually prepared by treatment of a phosphonium salt with a base, and phosphonium salts are usually prepared from the phosphine and an alkyl halide (10-44) ... 

---