Grignard reagents with aldehydes

Optically active B-substituted alkanoic acids are obtained by the reaction of the 6-alkylidene derivatives of (9), which are easily prepared from and aldehydes, with Grignard reagents in the presence of a catalytic amount of nickel chloride, followed... 

Treatment of aldehydes with Grignard reagents affords secondary alcohols in accord with the following scheme of addition ... 

The synthesis of allylic ethers from alkenes via electrochemical oxyselenenyla-tion has been mentioned earlier in this Report (Scheme 13). Details have appeared of the reaction of acetals of a,/3-unsaturated aliphatic aldehydes with Grignard reagents in the presence of TiCU to give allylic ethers in high yields [equation (12)] ° it was also found that the 2,4-dichlorophenoxy-group could... 

Chiral Lewis acid (55) derived from optically active 2,6-diarylphenol derivatives and MesAl was used in enantioselective alkylation of aldehydes with Grignard reagents (Scheme 6.40) [49]. The use of 3 equivalent of Lewis acid was needed... 

Addition of allylmagnesium chloride to the aldehyde 32a occurred with fair syn selectivity, producing the homoallylic alcohol 44. This inversion of facial selectivity in comparison with the other reactions of 32 (Scheme 10), and also with a wide range of other A -monoprotected a-amino aldehydes, with Grignard reagents 44,45 including allylic ones 46), have been rationalized with the. s>v7-selective chair-like transition state P (Scheme 13), involving a sterically controlled approach of the allylic nucleophile to the Re face of the carbonyl (Felkin-Anh) (41,42). 

The type of alcohol produced depends on the carbonyl compound Substituents present on the carbonyl group of an aldehyde or ketone stay there—they become sub stituents on the carbon that bears the hydroxyl group m the product Thus as shown m Table 14 3 (following page) formaldehyde reacts with Grignard reagents to yield pri mary alcohols aldehydes yield secondary alcohols and ketones yield tertiary alcohols... 

Osmium tetroxide, reaction with alkenes, 235-236 toxicity of, 235 Oxalic add, structure of, 753 Oxaloacetic acid, structure of, 753 Oxetane, reaction with Grignard reagents, 680 Oxidation, 233, 348 alcohols, 623-626 aldehydes, 700-701 aldoses, 992-994 alkenes, 233-236 biological, 625-626 phenols, 631 sulfides, 670 thiols, 668... 

Addition of alkynes to a-alkoxy aldehydes is most favorably performed with the corresponding zinc reagents (Table 12)46. As with Grignard reagents, the chelation-controlled addition of zinc alkynes proceeds with higher diastereoselectivity when diethyl ether rather than tetrahydrofuran is used as reaction solvent. 

Similar results are found with the threose derivatives 11 and 13. Both aldehydes can be readily synthesized in either enantiomeric form from l- and D-tartaric acid. The open-chain aldehyde 11 with Grignard reagents affords predominantly the all-.v> n(xj/o)-diastereomer 12. The steric demand of the nucleophile apparently does not affect the diastereoselectivity, and the extremely high selectivity observed with [(l,3-dioxolan-2-yl)methyl]magnesium bromide is attributed to the presence of the dioxolane moiety, which is thought to stabilize the a-chelated transition state. 

Acetals, " ketals, and ortho esters react with Grignard reagents to give, respectively, ethers and acetals (or ketals). The latter can be hydrolyzed to aldehydes... 

When gem-disubstituted epoxides (122) are treated with Grignard reagents (and sometimes other epoxides), the product may be 123, that is, the new alkyl group may appear on the same carbon as the OH. In such cases, the epoxide is isomerized to an aldehyde or a ketone before reacting with the Grignard reagent. Halohydrins are often side products. 

Similarly, the oxazoHdine (it,S)-147, obtained as a mixture of epimers at C2 from N,N-dibenzyl (it)-phenylalaninal and hl-benzyl (S)-valinol, reacted with Grignard reagents to form in situ the iminium ion 148, from which the diamino alcohols 149 were produced as a single diastereomer [71 ] (Scheme 23). On the other hand, when the oxazoHdine derived from the (S)-aldehyde was used, the diamino alcohol was obtained as a 70 30 mixture of diastereomers. Alhough the preparation of the primary 1,2-diamines was not explored in that paper, compoimds 149 would be the precursors of the syn 1,2-diamine... 

Traceless linker 60 based on a benzotriazole scaffold was reacted with amines and aldehydes to produce Mannich-type amine products [69]. Final product release was achieved by treatment with Grignard reagents (Scheme 29). 

Compounds 133, prepared by the condensation of benzotriazole with aldehydes R HO (R1 = H, Pr or Ph) and 7V-octylaminoacetonitrile, react with sodium tetrafluoroborate to give the cyanomethyl derivatives 134. The latter are de-cyanomethylated by the action of copper(II) sulphate. Treatment of 133 with Grignard reagents affords the analogues 135 (R2 = Ph or PhCH2) and thence the secondary amines 136130. 

It should be noted that, on reaction with Grignard reagents, aldehydes will produce secondary alcohols, whereas ketones will form tertiary alcohols. Often forgotten is the possibility of synthesizing primary alcohols by using formaldehyde as the substrate. 

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