Aldehyde unsaturated, synthesis

Vicario, J., Uria, U., Badia, D., Carrillo, L., Reyes, E., Pesquera, A. (2010). On water rtninium/enatnine catalysis organocatalytic enantioselective cyclopropanation of a,p-unsaturated aldehydes. Synthesis, 2010, 701-713. 

The 5-oxohexanal 27 is prepared by the following three-step procedure (1) 1,2-addition of allylmagnesium bromide to an a, / -unsaturated aldehyde to give the 3-hydroxy-1,5-diene 25, (2) oxy-Cope rearrangement of 25 to give 26, and (3) palladium catalyzed oxidation to afford 27. The method was applied to the synthesis of A -2-octalone (28), which is difficult to prepare by the Robinson annulation[25]. 

The formation of pyridine derivatives from a, P-unsaturated aldehydes and ammonia involves formation of three bonds during the ring synthesis. For example, with an a, P-unsaturated aldehyde, both 2,5-substituted as well as 3,4-substituted pyridines can be obtained, depending on whether a 1,2- (eq. 17) or 1,4-addition (eq. 18) occurs with ammonia. Reactions are performed in the vapor phase with catalysts. 

Dijbner-von Miller Synthesis. A much less violent synthetic pathway, the Dn bner-von Miller, uses hydrochloric acid or 2inc chloride as the catalyst (43). As in the modified Skraup, a,P-unsaturated aldehydes and ketones make the dehydration of glycerol uimecessary, and allow a wider variety of substitution patterns. No added oxidant is required. With excess aniline the reaction proceeds as follows ... 

The reactions of dichlorocarbene with morpholine and piperidine enamines derived from cyclopentanone and cyclohexanone have been reported to lead to ring expanded and a-chloromethylene ketone products (355,356). Similarly a-chloro-a, -unsaturated aldehydes were obtained from aldehyde derived enamines (357). Synthesis of aminocyclopropanes (353,359) could be realized by the addition of diphenyldiazomethane (360) and the methylene iodide-zinc reagent to enamines (367). 

This reaction has recently been exploited for the synthesis of 2,3-diarylthiophenes. Thus, P-chloro-a,p-unsaturated aldehyde 19 underwent reaction with ethylthioglycolate to produce 20. The production of 20 by this method enabled the synthesis of a number of derivatives for investigations of their use as anti-inflammatory agents. 

Although a number of reagents can be used to reduce an isoxazole ring, molybdenum hexacarbonyl31 was selected for use in this synthesis. The action of this reagent on 24 reduces the weak N-0 bond of the isoxazole ring and produces a //-amino-a,//-unsaturated aldehyde (i.e. a vinylogous formamide) (see Scheme 19). Intermediate 87 forms smoothly upon deprotection of the terminal acetylene carbon with basic methanol-THF. 

An alternative process for the synthesis of vinylepoxides was clearly needed, so reactions with stoichiometric amounts of chiral sulfide were investigated (Scheme 9.16a) [74]. Indeed, when benzyl sulfonium salt 20 was treated with unsaturated aldehydes, the ees and des were high in all cases, whereas the yields [75] were highly substrate-dependent. The same products could be formed by treatment of an unsaturated sulfonium salt with benzaldehyde, but the yields and se-lectivities were generally slightly lower. 

Synthesis of highly functionalized 3,4-dihydro-2H-pyrans by high-pressure Lewis-acid-catalyzed cycloaddition of enol ethers and a,/i-unsaturated aldehydes [83]... 

A highly diasteieoselective synthesis of substituted 1,2,3,4,4a,9,9a, 10-octahydroacridines 95 with five stereogenic centers has been achieved by domino imine condensation/intramolecular polar [4ti + 2k] cycloaddition of anilines and oo-unsaturated aldehydes 94 <96JPR(338)468>. 

---