Lewis Acid-Catalyzed Additions of (Benzotriazol-1-yl)diethoxymethane to Enol Ethers and Enamides. New Syntheses of β-Alkoxyalkanal and β-Aminoalkanal Acetals
Abstract:Addition of (benzotriazol-1-yl)diethoxymethane 11 to various acyclic and cyclic enol ethers and enamides produces the corresponding adducts, which were reacted with either NaAlH(4) or Grignard reagents to afford acyclic acetal-ethers (18a-f), cyclic alpha-(substituted)-beta-acetals (19a-c), amino-acetals (24a,b), and 1,3-amino-ethers (25), all known but previously difficult-to-access classes of compounds.
“…As the pyrrole ring is known to be a useful protecting group for primary amines, 27 the process at room temperature and high pressure can be considered to be a new access to optically active amino aldehydes, building blocks in biosynthesis and total synthesis of different alkaloids. 28 When the oxo process is applied at high temperature and low pressure, racemization is avoided and the regioselectivity is enhanced; this leads to a regioselective and stereospecific synthetic approach to optically active 5-alkyl-5,6-dihydroindolizine derivatives. 29 The unusual behavior of the N-allylpyrroles depicted here shows that the nature of the substrate is a crucial parameter for determining the selectivity of the rhodium-catalyzed hydroformylation reaction.…”
Rhodium-catalyzed hydroformylation of the chiral (S)-3-alkyl-3-pyrrol-1-ylprop-1-enes at 100 atmospheres total pressure and 25°C led to the preferential formation of the branched 3-alkyl-2-methyl-3-pyrrol-1-ylpropanals. At 30 atmospheres and 125°C, the linear 4-alkyl-4-pyrrol-1-ylbutanals were obtained: these aldehydes are not the final products, but evolve into more stable 5,6-dihydroindolizines, with the same optical purity as the starting olefins, via a domino cyclization-dehydration process. According to the generally accepted mechanism for rhodium-catalyzed hydroformylation, the regioselectivity, and then the final chemoselectivity, can be rationalized by taking into account that while at room temperature no b-elimination occurs, at high temperature the belimination involves the branched rhodium-alkyl intermediate only.According to the generally accepted mechanism for the rhodium-catalyzed hydroformylation of olefins, 1 metal hydride addition to the double bond to give an isomeric metal-alkyl intermediates is a key step. This step can be reversible or nonreversible, depending on the substrate nature and the reaction conditions. Under mild conditions, i.e. at room temperature, the insertion is a nonreversible step; this is very important, because the regioselectivity for the formation of the branched b and the linear l rhodium-alkyl intermediates determines the regioselectivity for the formation of the final aldehydes B and L, respectively (Scheme 1). In contrast, if the alkyl formation is reversible, the selectivity-determining step will occur later, i.e. at the stage of the addition of carbon monoxide to the tricarbonyl species to give the tetracarbonyl species, as demonstrated by theoretical calculations in the case of hydroformylation of 1,1-diphenylethene at 100°C. 2 Both electronic and steric effects determine the regioselectivity of the formation of rhodium-alkyl complexes (Figure 1). Indeed, the hydroformylation under mild conditions of vinylaromatic substrates such as styrene, 3 vinylfurans, 4 vinylthiophenes, 5 vinylpyrroles, 6 and vinylpyridines 7 always provides a large predominance of the branched isomer over the linear one (B/L = 95:5 for styrene). As far as oxygen-containing substrates are concerned, vinyl ethers provide a regioisomeric ratio B/L of ≥ 80:20. 8 Under the same conditions, alkenes with a-hydrogens (i.e., linear alk-1-enes) give the two regioisomers in an almost 1:1 molar ratio. 9 An oxygen in the b-position to the vinyl group favors the formation of the branched isomers, as observed for allyl ethyl ether (B/L = 70:30) and similar substrates. 8 The linear isomers largely predominate over the branched ones in the hydroformylation of 3-alkyl-substituted alk-1-enes (e.g., 3-methylbut-1-ene). 10
“…As the pyrrole ring is known to be a useful protecting group for primary amines, 27 the process at room temperature and high pressure can be considered to be a new access to optically active amino aldehydes, building blocks in biosynthesis and total synthesis of different alkaloids. 28 When the oxo process is applied at high temperature and low pressure, racemization is avoided and the regioselectivity is enhanced; this leads to a regioselective and stereospecific synthetic approach to optically active 5-alkyl-5,6-dihydroindolizine derivatives. 29 The unusual behavior of the N-allylpyrroles depicted here shows that the nature of the substrate is a crucial parameter for determining the selectivity of the rhodium-catalyzed hydroformylation reaction.…”
Rhodium-catalyzed hydroformylation of the chiral (S)-3-alkyl-3-pyrrol-1-ylprop-1-enes at 100 atmospheres total pressure and 25°C led to the preferential formation of the branched 3-alkyl-2-methyl-3-pyrrol-1-ylpropanals. At 30 atmospheres and 125°C, the linear 4-alkyl-4-pyrrol-1-ylbutanals were obtained: these aldehydes are not the final products, but evolve into more stable 5,6-dihydroindolizines, with the same optical purity as the starting olefins, via a domino cyclization-dehydration process. According to the generally accepted mechanism for rhodium-catalyzed hydroformylation, the regioselectivity, and then the final chemoselectivity, can be rationalized by taking into account that while at room temperature no b-elimination occurs, at high temperature the belimination involves the branched rhodium-alkyl intermediate only.According to the generally accepted mechanism for the rhodium-catalyzed hydroformylation of olefins, 1 metal hydride addition to the double bond to give an isomeric metal-alkyl intermediates is a key step. This step can be reversible or nonreversible, depending on the substrate nature and the reaction conditions. Under mild conditions, i.e. at room temperature, the insertion is a nonreversible step; this is very important, because the regioselectivity for the formation of the branched b and the linear l rhodium-alkyl intermediates determines the regioselectivity for the formation of the final aldehydes B and L, respectively (Scheme 1). In contrast, if the alkyl formation is reversible, the selectivity-determining step will occur later, i.e. at the stage of the addition of carbon monoxide to the tricarbonyl species to give the tetracarbonyl species, as demonstrated by theoretical calculations in the case of hydroformylation of 1,1-diphenylethene at 100°C. 2 Both electronic and steric effects determine the regioselectivity of the formation of rhodium-alkyl complexes (Figure 1). Indeed, the hydroformylation under mild conditions of vinylaromatic substrates such as styrene, 3 vinylfurans, 4 vinylthiophenes, 5 vinylpyrroles, 6 and vinylpyridines 7 always provides a large predominance of the branched isomer over the linear one (B/L = 95:5 for styrene). As far as oxygen-containing substrates are concerned, vinyl ethers provide a regioisomeric ratio B/L of ≥ 80:20. 8 Under the same conditions, alkenes with a-hydrogens (i.e., linear alk-1-enes) give the two regioisomers in an almost 1:1 molar ratio. 9 An oxygen in the b-position to the vinyl group favors the formation of the branched isomers, as observed for allyl ethyl ether (B/L = 70:30) and similar substrates. 8 The linear isomers largely predominate over the branched ones in the hydroformylation of 3-alkyl-substituted alk-1-enes (e.g., 3-methylbut-1-ene). 10
“…In the presence of Lewis acids, N -(diethoxymethyl)benzotriazole 750 undergoes addition to enol ethers to produce 1-(benzotriazol-1-yl)-1,3,3-trialkoxypropanes 751 . Reactions with Grignard reagents convert derivatives 751 into β-alkoxyalkanal acetals 752 <1997JOC700> . Scheme 118 …”
Section: Reactivity Of Substituents Attached To Ring Nitrogensmentioning
Selective reduction of the amide moiety of acyclic and macrocyclic amidoketals was studied in presence of various reagents (BH 3 . Me 2 S, iBuAlH 2 , Red-Al w , LiAlH 4 ). The best results were obtained with lithium aluminium hydride in the presence of triethylamine traces, whereas borane dimethyl sulfide gave rise to a partial ketal reduction of the acyclic compound and Red-Al w to a cleavage of the macrocyclic molecule accompanied by an unexpected trans-acetalization.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
