Keto aldehydes, selective

A new, versatile and selective synthesis of 6- and 7-substituted pteridines was reported by Rosowsky (73JOC2073). /3-Keto sulfoxides, which can be viewed as latent a keto aldehydes, react with (251) to give 6-substituted pterins, and the use of a-keto aldehyde hemithioacetals leads in a regiospecific synthesis to the isomeric 7-substituted pterins (equation 85). 

Because aldehydes react with aminofluorosulfuranes more readily than ketones, keto aldehydes can be selectively fluorinated at the formyl group [94, 183] Haloacetaldehydes react with DAST to give bis(l-fluorohaloethyl) ethers as the only or main products [170] (equation 96)... 

Another reagent which has found use in pinacolic coupling is prepared from VC13 and zinc dust.181 182 This reagent is selective for aldehydes that can form chelated intermediates, such as /1-formyl amides, x-amido aldehydes, a-phosphinoyl aldehydes,183 and y-keto aldehydes.184 It can be used for both homodimerization and heterodimerization. In the latter case, the more reactive aldehyde is added to an excess of the second aldehyde. Under these conditions, the ketal formed from the chelated aldehyde reacts with the second aldehyde. 

Trimethylamine oxide (6, 624 7, 507) or alkaline hydrogen peroxide selectively oxidizes 2 and 3 at the C B bond to give protected 3-keto aldehydes (6). 

Chiral 4,4-dialkyl-l-cyclopentenones.1 The chiral bicyclic lactam 2, derived from levulinic acid and 1, on monoalkylation exhibits slight if any selectivity regardless of the electrophile. However, a second alkylation exhibits high endo-selectivity. This product (3), after reductive cleavage, furnishes a keto aldehyde that is cyclized by base to a chiral 4,4-disubstituted-2-cyclopentenone (4). Either antipode of 4 can be prepared by the sequence of alkylation. 

Intramolecular Michael-aldol cyclization One route to a hydrindane involves base-catalyzed cyclization of the keto aldehyde 1 to the hydrindene 2. Although Zr(0-/-Pr)4 is useful, Zr(0-n-Pr)4 is the most satisfactory base, both in respect to yield and selectivity. 

When amino alcohols are used as the amine components along with glyoxal or a-keto-aldehydes, this process generates 2-hydroxy-morpholines 128 (Scheme 7.17) [62, 63], According to Carboni [63], this reaction proceeds with variable diastereo-selectivities (e.g. 129-131), and we have found that certain chiral amino alcohols give modest asymmetric induction (e.g. 132) [62]. 

For the same reason, reaction of the keto aldehyde with one equivalent of ethylene glycol selectively forms the acetal of the aldehyde functional group. The ketone can then be reduced with NaBFLj and the acetal protecting group can be removed. 

The 1,5-diketone formation by the Michael addition of allylsilane (48) to a, -unsaturated ketones was applied to the synthesis of (+)-nootkatone. Reaction of the keto group of keto aldehyde (58) with allyl Orignard reagent and dehydration gave the diene aldehyde (59). The selective oxidation of the terminal double bond afforded the 1,5-dica nyl compound (60), which is not stable and converted directly to pyridines and phenols (Scheme 18). ... 

Keto aldehyde 191 (Scheme 2.87) was prepared as a common precursor in the synthesis of a series of isoprenoid pheromones. One of the synthetic options required the selective reduction of a ketone carbonyl in this compound. Under mild conditions of acetalization (weak acid, methanol), only the aldehydic function of 191 was affected to form a mono-protected derivative, 192. Reduction of the keto group in the derivative with sodium borohydride and subsequent removal of the acetal protecting group gave the desired hydroxy aldehyde 193. ... 

Another interesting feature of the amphiphilic alkylation of carbonyl compounds using MAD is its chemoselectivity. For instance, in the alkylation of polyfunctional molecules such as keto-aldehydes 131, the aldehyde carbonyl was selectively methylated with the MAD-MeLi system to give the secondary keto alcohol 132 in 72 % yield (Sch. 93) [130]. 

Tetra-n-butylammonium triacetoxyborohydride in refluxing benzene reduced aldehydes but not acyclic ketones, the selectivity was demonstrated in competition experiments and keto aldehyde reductions. The more reactive cyclohexanones were reduced only slowly under the same conditions. The limitation of this convenient method is that proximal hydroxy groups activated the reagent enabling the... 

Selectively protected keto aldehyde (209) is prepared by KMn04 oxidation of (208). 

A novel one-pot Dess-Martin oxidation was developed for the construction of the y-hydroxy lactone moiety of the CP-molecules in the laboratory of K.C. Nicolaou. Bicyclic 1,4-diol was treated with 10 equivalents of DMP in dichloromethane for 16h to promote a tandem reaction first, the bridgehead secondary alcohol was selectively oxidized to the ketone, followed by a ring closure to afford the isolable hemiketal, which was further oxidized by DMP to give a keto aldehyde. Trace amounts of water terminated the cascade to give a stable diol, which was not further oxidized with DMP. Subsequent TEMPO oxidation furnished the desired y-hydroxy lactone. 

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