Hydroformylation/acetal formation

Acetalization of oxo aldehydes is used to protect sensitive aldehyde products, especially in asymmetric hydroformylation preventing racemization of an a-chiral aldehyde product [18-22,27]. Acetal formation can also be applied to the synthesis of monocyclic or spirocyclic pyranes as potential precursors and building blocks for natural products such as pheromones or antibiotics. A representative example is the synthesis of the pyranone subunit of the Prelog-Djerassi lactone. For this purpose, various 1,2-disubstituted homoal-lylic alcohols were used (Scheme 3) [32],... 

General Procedure for the Hydroformylation/N,N-acetal Formation. Synthesis of Biaza-cycloalkanes. The unsaturated diamine (leq), [Rh(OAc)2h (0.5 mol % Rh atoms) and BIPHEPHOS (2 mol %) were placed in an autoclave under N2 followed by deoxygenated benzene The vessel was flushed and evacuated three times with CO/H2 (1 1,13 bar) and then pressurized to 28 bar. The reaction was kept at 40-80 °C for 20h. The autoclave was cooled and the gases were released followed by selective extraction of the total product with light petroleum. Concentration of the solvent gave in most cases NMR pure material of the title compounds. 

Eilbracht et al. by means of rhodium-catalyzed tandem hydroformylation/acetalization of cccw-alkenediols [20]. It had been previously reported that hydroformylation of alkenol resulted in cyclic hemiacetal [21]. Starting from enediols, the authors paved the way for subsequent acetalization, leading to fused bicyclic compounds in a one-pot cascade. As expected, exclusive formation of czs-fused perhydrofuro[2,3fr]furan 6 occurred when applying 60 bar of syngas (CO H2 = 3 1) at 120 °C in dichloromethane to diol 5 in the presence of a [Rh(cod)Cl]2/PPh3 catalytic system (Scheme 4). 

Biphasic reaction conditions can be achieved within a wide range of operating conditions with respect to co-solvents. The most common co-solvents are the lower alcohols the purpose is to improve substrate solubility and as a consequence to increase reaction rate. Recent work with ethanol as a co-solvent shows that this is very effective at improving reaction rates [3]. It is estimated for example that the solubility of 1-octene in a 50 50 mixture of ethanol and water is 104 times greater than in water alone [3], In a comparison of several co-solvents - ethanol, methanol, acetone, and acetonitrile - it was found that ethanol was the most effective at improving reaction rates in the two-phase hydroformylation of 1-octene [4], Generally, though, the use of co-solvents in hydroformylation reactions with Rh/TPPTS catalysts is not advisable, because of diminished reaction selectivity and the possibility of acetal formation (see below). 

Homoallyl alcohols, such as 3-methyl-3-buten-l-ol, under the condition of n-regioselective hydroformylation at 3 bar, subsequent hemi-acetal formation, and final dehydration give rise to 3,4-dihydro-4-methyl-2//-pyran (Scheme 4.34) [76]. 

Figure 5.14 Rates of acetal formation In the Rh- or Ru-catalyzed hydroformylation-acetallzation.

Beginning with the only occasionally observed formation of acetals as final products of hydroformylation reactions, the hydroformylation-acetalization tandem reaction is nowadays one of the most important reactions in the framework of hydroformylation. Today, the undesired formation of acetals can be avoided by special setup of the reaction conditions. On the other hand, the tandem reaction is an important protocol for the protection of the carbonyl groups toward several... 

Hydroformylation is often accompanied by sequential or side reactions. Frequently found as sequential reactions are those already described aldol condensation and acetal formation, Tishenko type reactions as well as oligomeri2ation and polymerization. The hydrogenation of aldehydes to alcohols under hydroformylation conditions can also be included. 

The one-pot acetal formation in the rhodium-catalyzed styrene hydroformylation... 

Next, regioselective silyiation, reduction, and protection steps produced 288. Oxidative cleavage of C=C double bond and diastereoseiective crotylation with 290 gave intermediate 291. The latter was submitted to hydroformylation and acetate formation yielding product 292 (Scheme... 

Internal acetals are found in several biological active natural products such as di-hydroclerodin [209] and aflatoxins as 6/2-70 [210]. An efficient formation of this functionality was described by Eilbracht and coworkers [211], using a hydroformylation of an enediol as 6/2-71 to give the tetrahydrofurobenzofurans 6/2-72 (Scheme 6/2.15). 

Abstract Aldehydes obtained from olefins under hydroformylation conditions can be converted to more complex reaction products in one-pot reaction sequences. These involve heterofunctionalization of aldehydes to form acetals, aminals, imines and enamines, including reduction products of the latter in an overall hydroaminomethylation. Furthermore, numerous conversions of oxo aldehydes with additional C.C-bond formation are conceivable such as aldol reactions, allylations, carbonyl olefinations, ene reactions and electrophilic aromatic substitutions, including Fischer indole syntheses. 

Scheme 3 Formation of 0,0-acetals under hydroformylation conditions...

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