Reaction aminocarbonylation

The catalytic oxidative carbonylation of allene with PdCb and CuCh in MeOH affords methyl a-methoxymethacrylate (559)[499]. The intramolecular oxidative aminocarbonylation of the 6-aminoallene 560 affords the unsaturated J-amino ester 561. The reaction has been applied to the enantioselective synthesis of pumiliotoxin (562)[500]. A similar intramolecular oxycarbonyla-tion of 6-hydroxyallenes affords 2-(2-tetrahydrofuranyl)acrylates[501]. 

The main reaction of this type has been the reductive cyclization of nitropyridine derivatives carrying an o-amino ester or o-aminocarbonyl substituent. These cyclize in situ via the o-diamino derivative to give pyridopyrazines of known constitution, either for establishment of structure of products obtained in the ambiguous Isay synthesis (see Section 2.15.15.6.1), or in the synthesis of aza analogues of biologically active molecules. 

These reactions are related to the formation of pyrroles and quinolines from aminocarbonyl compounds and acetylenes (582,583) and may be contrasted with the formation of pyran derivatives by electrophilic attack on an enamine, followed by addition of an oxygen function to the imonium carbon (584-590). 

A highly diastereoselective alkenoylation of protected optically active a-hydroxy- and a-aminoalkanals is achieved with (alkyl-substituted) [1-(diisopropylaminocarbonyloxy)-l-[(4-tnethylphenyl)sulfonyl]-2-alkeuyl]lithium,1 ,2, generated by deprotonation with butyllithi-um in THF. During the reaction, the aminocarbonyl residue migrates and 4-methylbenzenesul-finate is eliminated. 

These reactions occur, presumably, via cyclic transition states with preferential placement of the allylic diisopropylcarbamate substituent in an equatorial position. The ( )-.vi -diastcreomer is available with much greater stereoselectivity by using the corresponding 1-diisopropyl-aminocarbonyl-2-propenyltitanium reagent (see Section D.1.3.3.3.8.)fi. 

YAMAGUCHi N (1988) Aminocarbonyl reaction. Antioxidant activity of the reactants, eg in biscuits, rice confectionery, sausages and margarine , Shokuhin-no Hoso, 20 (1) 41-8. 

Murphy, E.R., MartineUi, LR-, Zaborenko, N., Buchwald, S.L., Jensen, K.F. (2007) Accelerating Reactions with Micro-Reactors at Elevated Temperatures and Pressures Profiling Aminocarbonylation Reactions. Angewandte Chemie, 119(10), 1764-1767. 

Reaction of iV-aminocarbonyl-2-phenylethylamines with mesityl oxide and 2-butenal afforded l,2,3,6,7,llb-hexahydro-477-pyrimido[6,l- ]isoquinoline-4-ones <2003MC278>. 9,10-Dimethoxy-l,2,3,6,7,llb-... 

In a more recent report, Larhed and coworkers have presented microwave-mediated fluorous reaction conditions for palladium-catalyzed aminocarbonylations [100]. 

Murphy ER, Martinelli JR, Zaborenko N, Buchwald SL, Jensen KF (2007) Accelerating reactions with microreactors at elevated temperatures and pressures profiling aminocarbonylation reactions. Angew Chem Int Ed 46 1734-1737... 

The Pd-catalyzed carbonylation of 2,6-dibromopyridine in the presence of 2-pyridylamine gave N,lV -di(2-pyridyl)pyridine-2,6-dicarboxamide under relatively high pressure and prolonged reaction time [156]. Partial aminocarbonylation of 2,6-dibromopyridine was more cumbersome—only 55% of the monocarboxamide 195 was isolated in a shorter reaction time accompanied by the corresponding 2,6-dicarboxamide in 32% yield. 

As previously discussed, the Pd-catalyzed reactions of 2,5-dibromopyridine including Sonogashira, Negishi, and alkoxycarbonylation all take place at C(2). It has also been demonstrated that aminocarbonylation of 2,5-dibromo-3-methylpyridine occurred regioselectively at C(2) to afford 196 despite the steric hindrance of the 3-methyl group [157]. 

Aside from alkoxycarbonylations, hydroxycarbonylations in the presence of water to yield allenic carboxylic acids [15] (93, Y = OH) and aminocarbonylations in the presence of amines to give the analogous amides [139] (93, Y = NRR ) have also been carried out, respectively (Scheme 7.13). These products of structure 102 can also be obtained if using the propargylamines 101 with R1 = Ph or R3 Z H as starting materials (Scheme 7.15) [140]. Additionally, hydroxycarbonylations, also termed carboxyla-tions, are successful without palladium catalysis by reaction of propargyl halides and carbon monoxide in the presence of nickel(II) cyanide under phase-transfer conditions [141, 142]. 

Dioxotetrahydropyrimidine-5-carboxylates (1341) were prepared in 50-72% yields, by the cyclization of (V-(aminocarbonyl)aminomethy-lenemalonates (1340) in alcohol by the action of sodium alcoholate, or in 48-97% yields in the reaction of /V-substituted urea and EMME in ethanol in the presence of sodium ethylate at room temperature for several days. Compounds 1341 were also prepared in 41 and 62% yields, respectively, in the reactions of N-methyl- and /V,N -dimethylurea and EMME in the melt at 120°C for 24 hr (52JA4267). 

Abstract Development in the field of transition metal-catalyzed carbonylation of epoxides is reviewed. The reaction is an efficient method to synthesize a wide range of / -hydroxy carbonyl compounds such as small synthetic synthons and polymeric materials. The reaction modes featured in this chapter are ring-expansion carbonylation, alternating copolymerization, formylation, alkoxycarbonylation, and aminocarbonylation. 

Aminocarbonylation can also be carried out by use of CO and a silyl amide. Watanabe et al. reported the cobalt-catalyzed aminocarbonylation of epoxides [55]. Some silyl amides such as PhCH2NHSiMe3 and Et2NSiMe3 were applicable to the reaction to give the /i-siloxy amide in good yields, whereas high reaction temperature was required. The use of 4-(trimethylsilyl) morpholine was found to be crucial for a milder and more efficient carboami-nation here, the reaction proceeded at ambient temperature under 0.1 MPa of CO. However, N-(2-hydroxyalkyl)morpholines, a product without carbonyla-tion, were yielded as by-products (Scheme 18) [56]. 

T. Komano worked with him. The work accomplished at that time included the following N-debenzyloxycarbonylation of 1,3,4,6-tetra-0-acetyl-2-(benzyloxycarbonyl)amino-2-deoxy-D-hexopyranoses in the conversion of a,/3-acetoxy to glycosyl bromide (1961) oxidative cleavages of 1,2-diamino sugars and their significance in the mechanism of the aminocarbonyl reactions (1962) and synthesis of 2-amino-2-deoxy-/3-o-glucosides via 3,4,6-tri-D-acetyl-2-benzylsulfonamido-2-deoxy-a-D-glu-copyranosyl bromide (1962). 

Other interesting examples of these amino-exchange reactions are the conversion of 3-aminocarbonyl-4-R-l-(2,4-dinitrophenyl)pyridinium salt (2) into 3-aminocarbonyl-4-R-l-cbutylpyridinium salt by Cbutylamine (82RTC342) and the preparation of l-(pentadeuteriophenyl)-3-amino-carbonyl-4-deuteriopyridinium salt from 3-aminocarbonyl-l-(2,4-dinitro-phenyl)-4-deuteriopyridinium salt (2, R = D) with pentadeuterioaniline (84T433) (Scheme IIL2). 

The occurrence of this Sn(ANRORC) process has also been substantiated by N-labeUng experiments. Reaction of 3-aminocarbonyl-l-methylpyridinium salt (5, R = CONH2, Alkyl = CH3) with N-labeled liquid ammonia gives incorporation of the label into the pyridine ring (Scheme III.5) (84T433). 

Not only cyanide but also an isocyanide behaves as a nucleophile to attack a carbonyl compound or an imine that is prepared in situ from an carbonyl compound. " In these reactions, an isocyanide is a synthetic equivalent to an aminocarbonyl anion. Asymmetric version of this reaction appeared in 2003. Using a combination of Lewis acid SiCU and a Lewis base chiral bisphosphora-mide, the corresponding a-hydroxyamide is obtained in 96% yield with >98% ee (Scheme 4.23). 

Table 1 Overview of aminocarbonylation reactions performed under microreaction conditions...

Scheme 11 The aminocarbonylation reaction performed in a microflow reactor [33] toluene, base...

The Mannich reaction consists on the condensation of a CH-activated compound with a primary or a secondary amine and a non-enolizable aldehyde or ketone to afford p-aminocarbonyl derivatives known as Mannich bases (Scheme 20). This sequence is of great use for the constmction of heterocyclic targets, as illustrated for example by the Robinson-Schopf synthesis of tropinone in 1937 or by the preparation of some azabicyclo[3.3.1]nonanones or pyranocoumarine derivatives (Fig. 1) [100]. In the following, representative recent examples of the formation of five- to seven-membered ring heterocycles will be presented. 

Aminocarbonylation Reactions without Using Gaseous Carbon Monoxide... 

This chapter covers the recent advances in amidocarbonylations, cyclohydrocarbonylations, aminocarbonylations, cascade carbonylative cyclizations, carbonylative ring-expansion reactions, thiocarbonylations, and related reactions from 1993 to early 2005. In addition, technical development in carbonylation processes with the use of microwave irradiation as well as new reaction media such as supercritical carbon dioxide and ionic liquids are also discussed. These carbonylation reactions provide efficient and powerful methods for the syntheses of a variety of carbonyl compounds, amino acids, heterocycles, and carbocycles. 

Aminocarbonylation provides an efficient method for the synthesis of carboxamides from readily available alkenyl halides. This reaction finds many applications in organic synthesis, especially for the introduction of amides with a variety of A -substituents. For example, steroidal alkenyl iodide 137 was transformed to the corresponding amide derivative 138 in 88% yield through aminocarbonylation (Equation (10)). In this reaction, the palladium catalyst was recovered by using an ionic liquid, l-butyl-3-methylimidazolium salt 139, as reaction media, and reused five times with only a minor loss of activity. ... 

Aminocarbonylation has also been applied to the synthesis of unsymmetrical ferrocene-1,1 -bis-carboxamides. Ferrocene-based chiral ligands are very useful in asymmetric catalysis, and enantiomerically pure ferrocenyl ligands can be obtained by optical resolution of unsymmetrically substituted ferrocenes. However, the synthesis of such unsymmetrical ferrocenes is not an easy task. The use of aminocarbonylation gave a solution to this challenge. For example, the Pd-catalyzed reaction of symmetrical ferrocenyl diiodide 144 with two different amines, morpholine and diethylamine (5 equiv. each) under 39.5 atm of CO, gave the desired unsymmetrically disubstituted ferrocene-biscarboxamide 145 in 85% yield (Equation (11)). ... 

Since formamide is a weak nucleophile, the use of imidazole or 4-dimethylaminopyridine (DMAP) is necessary for acyl transfer to formamide via an activated amide (imidazolide) or acylpyridinium ion. As Scheme 22 illustrates, the reaction starts with the oxidative addition of aryl bromide 152 to Pd(0) species, followed by CO insertion to form acyl-Pd complex 154. Imidazole receives the aroyl group to form imidazolide 155 and liberates HPdBr species. Then, imidazolide 155 reacts with formamide to form imide 156. Finally, decarbonylation of imide 156 gives amide 157. In fact, the formations of imidazolide intermediate 155 and imide 156 as well as the subsequent slow transformation of imide 156 to amide 157 by releasing CO were observed. This mechanism can accommodate the CO pressure variations observed during the first few hours of aminocarbonylation. When the reaction temperature (120 °C) was reached, a fast drop of pressure occurred. This corresponds to the formation of the intermediary imide 156. Then, the increase of pressure after 3 h of reaction was observed. This phenomenon corresponds to the release of CO from imide 156 to form amide 157. ... 

In connection with the aminocarbonylation processes described above, an apparent CO-free aminocarbonylation reaction of aryl and alkenyl iodides was reported using A, Wdimethylformamide (DMF) as the ammonia substitute in the presence of phosphorus oxychloride (POCI3) (Scheme 23). This reaction is so far restricted to DMF at present. 

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