Hydroxymethylation of Aldehydes and Ketones

L-Prohne catalyzes the direct hydroxymethylation of aldehydes and ketones, though with low yields [116]. Higher yields and enantioselectivities are generated by a,a-diphenylprolinol trimethylsilyl ether [117]. The desired a-substituted P-hydroxymethylated products are not stable and have to be converted to more readily isolable derivatives. This method should be the first choice for synthesis of a-hydroxymethylated aldehydes since it is suitable for large scales (75.8 g of aldol). 

Metalated cyclic aldo-nitrones are characterized by high reactivity toward electrophilic reagents. Reactions with aldehydes and ketones afford satisfactory yields of a-hydroxymethyl substituted derivatives of nitrones (551). The reactions were also carried out with a number of aliphatic, aromatic, and hetero-aromatic aldehydes and ketones (Schemes 2.124 and 2.125). 

Alkylfurans are usually obtained by ring synthesis, decarboxylation of alkylfurancarboxy-lic acids, Wolff-Kishner reduction of aldehydes or ketones, or by reduction of halomethyl groups with zinc and acetic acid or LAH (79JOC3420) alkylation is of limited value. The chemistry of these compounds is conventional but oxidation to furancarboxylic acids cannot usually be carried out due to the lability of the ring. NBS bromination (Section 3.11.2.2.5) is a useful route to side-chain substituted compounds but reduction of esters to hydroxymethyl groups and subsequent transformation is often preferable. The haloalkyl compounds are extremely sensitive to resinification but if adequate precautions are taken they are... 

Several representative examples of nucleophilic hydroxymethylation of aldehydes, ketones, organic halides, tosylates, and epoxides are summarized in Table I. The oxidation conditions given in the original literature are not necessarily optimum, and results may be improved by use of the oxidation method employed here. These results, summarized in Table I, demonstrate the general applicability of the silicon-based nucleophilic hydroxymethylation. 

Nucleophilic Hydroxymethylation of Aldehydes, Ketones, Organic Halides, Alcohols, and Epoxides.8... 

A very convenient hydroxymethylation process has been developed based on the Sml2-mediated Bar-bier-type reaction. Treatment of aldehydes or ketones with benzyl chloromethyl ether in the presence of Smh provides the alkoxymethylated products in good to excellent yields. Subsequent reductive cleavage of the benzyl ether provides hydroxymethylated products. Even ketones with a high propensity for enolization can be alkylated by this process in reasonable yields. The method was utilized by White and Soners as a key step in the synthesis of ( )-deoxystemodinone (equation 27). This particular ketone substrate resisted attack by many other nucleophilic reagents (such as methyllithium) owing to conpeti-tive enolate formation. 

The cathodic dimerization of aromatic aldehydes and ketones in slightly acidic medium via ketyls or hydroxymethyl radicals is a powerful method for the preparation of pinacols in good to excellent yields, e.g. 98 [148a], 99 [148b] or 100 [148c]. Correspondingly, the heteroanologous azomethines, pyrimidines, quinazolines and immonium ions can be hydrodimerized, presumably also via radicals [149],... 

Trichloro-2-thienyllithium prepared from tetrachlorothiophene by lithium-chlorine exchange (Bu"Li) reacted with aldehydes and ketones to generate carbinols. Treatment of the (2-hydroxymethyl) trichlorothiophene (406) with catalytic TsOH in refluxing benzene gave the electrophilic substitution product (407). Replacement of benzene with nitrobenzene as solvent led to... 

Formation of carbonyl compound derivatives Hasan Mehdi et al. [29] reported the use of imidazolium ILs as solvents for organic transformations with tetravalent cerium salts. Urea-hydrogen peroxide in the presence of catalytic amoimt of magnesium bromide efficiently oxidizes primary and secondary benzylic alcohols into the corresponding aromatic aldehydes and ketones [30]. Margarida M. Antrmes et al. [31] reported IL 1-butyl-3-methylimidazolium chloride ([bmim]Cl) as solvent, in the transformation of o-glucose into 5-(hydroxymethyl)-2-furaldehyde at 120 °C. 

The organometallic species formed by treatment of trimethylsilylpropargyl bromide (160) with aluminium amalgam condenses regioselectively with aldehydes and ketones to give a-hydroxymethyl(trimethylsilyl)allenes (161). ° ... 

---