Branched aldehydes

A fluorine-hydrogen migration is typical for the reactions of aldehydes branched at the carbon atom a to the formyl group. Comparable amounts of 1,1 -difluoroalkanes and 1,2-difluoroalkanes together with bis(l -fluoroalkyl) ethers are obtained [169] (equation 84). 

In contrast to the normal-scXcctwc hydroformylation mainly developed in industry, asymmetric hydroformylation, which requires /i o-aldehydes ( branched aldehydes) to be formed from I-alkenes, was first examined in the early 1970s by four groups independently, using Rh(i) complexes of chiral phosphines as catalysts. " Since then, a number of chiral ligands have been employed for asymmetric hydroformylation and used in combination with transition metal ions, especially Pt(ii) and Rh(i). Asymmetric hydroformylation of I-alkenes is most extensively studied. 

Once again proline functions as organocatalyst furnishing the desired aldol adducts 80 in yields of 41 to 85%. With the exception of alkylated aldehydes branched in the a-position, however, d.r. ratios were low, although good to excellent enantioselectivity of 85 to 97% ee was observed for all aldehydes, irrespective of their substitution pattern. The best result was obtained with isobutyraldehyde this afforded the anti-aldol product 80b in 68% yield, with diastereoselectivity of d.r. > 20.1, and enantioselectivity of 97% ee [94, 95]. 

The work of Baddiley and coworkers and of Bruton and Horner with labelled precursors in connection with the biosynthesis of L-streptose (25) from streptomycin has been reviewed.4,6,36 It was found that the aldehyde branch of streptose originates from C-3 of glucose, and that the hexose unit as a whole is incorporated into the streptose molecule (see Scheme 9). 

As shown in the Table, aldehyde branching in the a-position does not affect markedly the reaction yield or stereoselectivity. The relative efficiency of the sulfones remained, in principle, the same. 

At 220 °C peracid or peracid/aldehyde branching is still probable, and since for high O2/C2H5CHO ratios the kinetics resemble those obtained below 150 °C, the overall mechanism is almost certainly the same as that at the lower temperatures with additional complications arising from RCO decomposition and the subsequent reactions of C2H5 radicals. Since the amount of CO2 produced after the peracid maximum (Fig. 27) is approximately the same as the amount of peracid lost, it seems reasonable to suppose that, as at the lower temperature, CO2 is produced in the branching process. 

Water (%) Yield (%) Linear aldehyde Branched aldehyde TOF (h- )... 

Conventionally, this reaction is conducted in the presence of a Lewis acid. We had to check that the catalyst used in the hydroformylation was still active in the presence of such an acidic additive. To this point, only catalytic amounts of PPTS (pyridinium p-toluenesulfonate) had been used in CHC reactions. This study was conducted on substrate 21, which was designed to allow only the hydroformylation/cyclization sequence (Scheme 9). It was synthesized by peptide coupling between 0-Me-phenylglycinol and vinyl acetic acid in a yield of 84%. Without an acidic additive, the hydroformylation reaction of this substrate proceeded in 93% yield and produced the linear aldehyde/branched aldehyde in a ratio of 92 8. We obtained the enamide after the CHC reaction in very good yields both in the presence of pTSA and Lewis acids (e.g., BF3-Et20, Zn (OTf)2). In addition, it should be noted that the regioselectivity of the hydroformylation reaction dictated by chelation of the BiPhePhos ligand is not disturbed by the presence of the acidic additive. 

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