Unsymmetrical aldehydes, synthesis

The Hantsch pyridine synthesis provides the final step in the preparation of all dihydrop-yridines. This reaction consists in essence in the condensation of an aromatic aldehyde with an excess of an acetoacetate ester and ammonia. Tlie need to produce unsymmetrically subsrituted dihydropyridines led to the development of modifications on the synthesis. (The chirality in unsymmetrical compounds leads to marked enhancement in potency.) Methyl acetoacetate foniis an aldol product (30) with aldehyde 29 conjugate addition of ethyl acetoacetate would complete assembly of the carbon skeleton. Ammonia would provide the heterocyclic atom. Thus, application of this modified reaction affords the mixed diester felodipine 31 [8]. 

The asymmetric synthesis of unsymmetrical vicinal diamines by samarium diiodide induced reductive coupling of nitrones derived from aUphatic aldehydes with optically pure N-tert-butanesulfinyl aromatic imines has been recently reported [41]. For example, the reaction between nitrone 55 and... 

A closely related protocol for the synthesis of imidazoles was independently investigated by Sparks and Combs (Scheme 6.199) [362]. Here, the authors employed readily available unsymmetrical keto-oximes as building blocks, initially leading to N-hydroxyimidazoles. Diaryl keto-oximes were condensed with various aldehydes (1.1 equivalents) in the presence of 4 equivalents of ammonium acetate under microwave conditions at 160 °C. In this way, the N-hydroxyimidazoles were formed... 

SYNTHESIS OF UNSYMMETRICAL BIARYLS USING A MODIFIED SUZUKI CROSS-COUPLING 4-BIPHENYLCAR BOX ALDEHYDE ([1,1 -Biphenyl]-4-carboxaldehyde)... 

Ether synthesis.5 Unsymmetrical ethers can be obtained from an aldehyde or ketone and an alkoxytrimethylsilane with trityl perchlorate (equation I). 

The method has been extended to include the synthesis of aldehydes or of unsymmetrical ketones by using appropriate mixtures of carboxylate salts. 

Ariza took advantage of the use of acetylides for preparation of unsymmetrical 1,4-diols, adopting it to the synthesis of the natural product musclide B [27]. He also showed for a number of different aldehydes that by correct choice of the enantiomeric ligand the diastereomeric, protected diols were accessible in 87 13 to 98 2 diastereoselective ratios (Eq. 22). 

Scheme 95 describes in principle the same synthesis technique using a bisphospho-nium salt 562 as the central molecular part of the molecules 563 and 565. Olefination of the ylide generated from 562 with two equivalents of the ketoaldehyde 561 yields ketocarotenoid 563211). Unsymmetrical ketocarotenoid 565 has been synthesized by the Wittig reaction of 562 with a mixture of aldehydes 564 and 511 and subsequent hydrolysis of the acetal protective group 271) (Scheme 95). 

---