Alcohols synthesis from acyl compounds

Enantioenriched alcohols and amines are valuable building blocks for the synthesis of bioactive compounds. While some of them are available from nature s chiral pool , the large majority is accessible only by asymmetric synthesis or resolution of a racemic mixture. Similarly to DMAP, 64b is readily acylated by acetic anhydride to form a positively charged planar chiral acylpyridinium species [64b-Ac] (Fig. 43). The latter preferentially reacts with one enantiomer of a racemic alcohol by acyl-transfer thereby regenerating the free catalyst. For this type of reaction, the CsPhs-derivatives 64b/d have been found superior. 

Organopalladium intermediates are also involved in the synthesis of ketones and other carbonyl compounds. These reactions involve acylpalladium intermediates, which can be made from acyl halides or by reaction of an organopalladium species with carbon monoxide. A second organic group, usually arising from any organometallic reagent, can then form a ketone. Alternatively, the acylpalladium intermediate may react with nucleophilic solvents such as alcohols to form esters. 

Formylfuran reacts with potassium cyanide in alcohol solution to give a product containing two furan nuclei. What is this product and how does it form Can you suggest an alternative synthesis of the compound from 2-formylfuran using propane-1,3-dithiol as one reagent Hint consider an acyl anion equivalent approach). 

In a series of papers [23], Tamai et al. reported using l,r-binaphthyl isomers as templates for a diastereoselective synthesis of ester alcohols from the corresponding acyl compounds. They reported a low d.e. of 16% of the ester alcohol [Eq. (8) 23c]. However, their more recent modifications gave improved yields and higher diastereoselectivities. When they added a polyether as a 2 -substituent and lengthened the chain between the dicarbonyls, the 7 -isomer was formed exclusively. Hydrolysis of this product yields the / -lactone. The authors suggest that the cooperative chelation of the oxygen side chain plays an important role in the exclusive formation of the / -enantiomer. 

Keto esters and amides are versatile intermediates in organic synthesis and often are prepared from acyl Meldrum s acid adducts. This method involves formation of acyl Meldrum s adducts by reaction of Meldrum s acid with activated carboxylic acids followed by decarboxylation in the presence of nucleophiles such as alcohols or amines (Scheme 21.2). The ability of readily available acyl Meldrum s acids to react with various nucleophiles allows quick access to a variety of functionalized compounds. Apphcation of this methodology in synthetic chemistry has been widely exploited. For example, acyl Meldrum s adducts can react with imines to prepare pyridinones or... 

Based on the Amaryllidaceae alkaloid galanthamine, a biomimetic solid-phase synthesis of 2527 compounds was reported by Shair and coworkers (Figure 11.13) The core scaffold, initially prepared in several steps, was diversified by means of four successive reactions Mitsunobu reaction of the phenolic moiety with five primary alcohols, Michael addition of the a, 3-unsatnrated cyclohexenone with thiols, iV-acylation or A -alkylation of the cyclic secondary amine, and treatment of the ketone with hydrazines and hydroxylamines. Further evaluation of library constituents for their ability to block protein trafficking in the secretory pathway of mammalian cells led to the discovery of sercramine as a potent inhibitor of the VSVG-GFP protein movement from the Golgi apparatus to the plasma m brane. 

Another method used to remove phosgene substitutes from the desired products is to destroy them with appropriate nucleophiles such as water or alcohols. This method can, of course, only be applied when the product is insensitive to these nucleophiles, as is the case for carbamates, carbonates, ureas, cyanides, isocyanides, and alkyl chlorides. Chloroformates, carbamoyl chlorides, isocyanates, acyl chlorides, N-carboxylic anhydrides, and carbodiimides, on the other hand, cannot be purified by this method. Consequently, a synthesis of these compounds using phosgene is worthy of consideration. 

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