N-Aryl carbamates

PREPARATION OF N-ARYL-5R-HYDROXYMETHYL-2-OXAZOLIDINONES FROM N-ARYL CARBAMATES N-PHENYL-(5R)-HYDROXYMETHYL- 2-OXAZOLIDINONE... 

Table 3.26 lists illustrative examples of cleavage reactions of support-bound N-aryl-carbamates, anilides, and /V-arylsulfonamidcs. /V-Arylcarbamatcs are more susceptible to attack by nucleophiles than /V-alkylcarbamates, and, if strong bases or nucleophiles are to be used in a reaction sequence, it might be a better choice to link the aniline to the support as an /V-bcnzyl derivative. Entry 7 (Table 3.26) is an example of a safety-catch linker for anilines, in which activation is achieved by enzymatic hydrolysis of a phenylacetamide to liberate a primary amine, which then cleaves the anilide. 

The alkylation of carbamates and ureas is similarly difficult as the alkylation of amides. Non-deprotonated carbamates or ureas are weak nucleophiles which will react only with carbocations or other, similarly reactive alkylating agents. Metalated carbamates and ureas, on the other hand, are strong bases but poor nucleophiles, and most of the reported examples of their alkylation are limited to methylations, allylations, or benzylations, or to cyclic carbamates and ureas. Two examples of the alkylation of N-aryl carbamates are given in Scheme 6.26. 

Similarly, on-column methylation has been applied to carbamate pesticides containing an active N-H group. Wien and Tanaka (41) showed that N-aryl carbamates are methylated on-column with tri-methylanilinium hydroxide-methanol to give the intact N-methyl and N-aryl derivatives. On the other hand N-methyl, 0-aryl carbamates such as carbaryl or carbofuran yielded only the methyl ethers of their respective phenols. This work has now been extended to sulfur-containing carbamates such as methomyl, methio-carb, aldicarb, etc. (42-43). Here the oxime hydrolysis products of these carbamates are chromatographed as the 0-methyl oximes. 

Prior to the recent paper by Buchwald, an intermolecular version of the arylation of carbamates was published by Hartwig et al. (Eq. (22)) [163]. His group showed that reactions catalyzed by a combination of Pd(OAc)2 and P(tBu)3 formed N-aryl carbamates from aryl bromides or chlorides and tert-butyl carbamate, but that this system was inactive for reactions of amides or sulfonamides. Again, the reaction conditions were not as mild as those used for animation, but they were similar to those employed in the reactions with Xantphos. For the intermolecular reactions, the use of sodium phenoxide as base was crucial. 

In the special case of alkaline hydrolysis of N-substituted aryl carbamates, there is another mechanism involving elimination-addition ... 

This mechanism does not apply to unsubstituted or N,N-disubstituted aryl carbamates, which hydrolyze by the normal mechanisms. Carboxylic esters substituted in the a position by an electron-withdrawing group (e.g., CN or COOEt) can also hydrolyze by a similar mechanism involving a ketene intermediate. These elimination-addition mechanisms usually are referred to as ElcB mechanisms, because that is the name given to the elimination portion of the mechanism (p. 1308). 

The mechanism of the stereoselective syntheses of (K)-3-aryl-5-(hydroxy-methyl)oxazolidinones via the Mannenin reaction of aryl carbamic acid esters with (Jt)-glycidyl butyrate has been explored in detail by Brickner et al. [60]. Namely, N-lithiated carbamate derivatives of anilines are allowed to react with the commercially available (K)-glycidyl butyrate (96-98% enantiomeric excess ee) under appropriate conditions to obtain enantiomerically pure (Jt)-3-aryl-5-(hydroxymethyl)oxazolidinones in 85-99% yields, according the pathways depicted in Scheme 19. 

The first reported synthesis of hydroxyurea (24) consists of the condensation of hy-droxylamine with potassium cyanate (Scheme 7.14) [87]. Condensation of hydroxy-lamine with ethyl carbamate also gives pure hydroxyurea in good yield after recrystallization (Scheme 7.14) [88]. Nitrogen-15 labeled hydroxyurea provides a useful tool for studying the NO-producing reactions of hydroxyurea and can be prepared by the condensation of N-15 labeled hydroxylamine with either potassium cyanate or trimethylsilyl isocyanate followed by silyl group removal (Scheme 7.14) [89, 90]. Addition of hydroxylamine to alkyl or aryl isocyanates yields alkyl or aryl N-hydroxyureas (Scheme 7.14) [91, 92]. The condensation of amines with aromatic N-hydroxy carbamates also produces N-substituted N-hydroxyureas (Scheme 7.14) [93]. 

Only few types of benzyUithium compounds being configurationally stable in solution at —78°C are known lithium-TMEDA complexes of secondary 0-benzyl Af,Af-dialkyl carbamates, such as 211 or the 2,4,6-triisopropylbenzoate 212 ° , of secondary N-aryl-Af-Boc-benzylamines (213) and the dUithio-(—)-sparteine derivative 214 . ... 

The transition metal catalyzed synthesis of arylamines by the reaction of aryl halides or tri-flates with primary or secondary amines has become a valuable synthetic tool for many applications. This process forms monoalkyl or dialkyl anilines, mixed diarylamines or mixed triarylamines, as well as N-arylimines, carbamates, hydrazones, amides, and tosylamides. The mechanism of the process involves several new organometallic reactions. For example, the C-N bond is formed by reductive elimination of amine, and the metal amido complexes that undergo reductive elimination are formed in the catalytic cycle in some cases by N-H activation. Side products are formed by / -hydrogen elimination from amides, examples of which have recently been observed directly. An overview that covers the development of synthetic methods to form arylamines by this palladium-catalyzed chemistry is presented. In addition to the synthetic information, a description of the pertinent mechanistic data on the overall catalytic cycle, on each elementary reaction that comprises the catalytic cycle, and on competing side reactions is presented. The review covers manuscripts that appeared in press before June 1, 2001. This chapter is based on a review covering the literature up to September 1, 1999. However, roughly one-hundred papers on this topic have appeared since that time, requiring an updated review. 

We have used organo-phosphorus acids [25] as promoters of the reaction of aromatic amines with dimethylcarbonate (DMC) or diphenylcarbonate (DPC) in the presence of carbon dioxide to generate N-alkyl- or aryl-carbamates. We have applied this methodology to the carbamation of aniline, naphtylamine, toluen-diamine, 4,4 -diaminophenyl-methane, among others. 

N-Arylaminophthalimides, hydrazines, hydrazones, and N-H containing heterocycles are N-arylated by combined use of Ar3Bi and Cu(OAc)2 (Scheme 14.134) [281] in which Cu(OAc)2 oxidizes Ar.l i to Ar jl i(OAc)2 and catalyzes the arylation via transmetalation (Section 14.3.4.2). The Cu(OAc)2-promoted N-arylation of amides, sulfonamides, ureas, carbamates, and anilines with ArsBi proceeds efficiently in the presence of EtsN or pyridine (Scheme 14.135) [282]. N-Arylation occurs selectively on the primary amino group of aminobenzanilides (Scheme 14.136) [283]. A variety of amines are N-alkylated in moderate yields by use of alkylbismuthanes assisted by Cu(OAc)2 [284]. 

Aromatic amines have been shown to be intermediates in the metal catalyzed carbonylation of nitroaromatics to aryl carbamates. Previous research established that the novel bis(methoxycarbonyl) complex, Ru(dppe)(C0)2[C(0)0Me]2, was the most abundant species present during catalysis. In this study, the complete kinetic analysis of the reaction of p-toluidine with Ru(dppe)(C0)2[C(0)0Me]2 established that the C-N bond formed by nucleophilic attack on a metal carbonyl, and that the organic product was removed from the metal by an intramolecular elimination of aryl isocyanate. 

By employing o-(trimethylsilyl)phenyl triflate derivatives (11) as the aryne precursors, Larock and coworkers have developed a facile transition metal-free N-arylation method for amines, sulfonamides and carbamates under very mild reaction conditions (Scheme 12.4) [11]. Aromatic and aliphatic, as well as primary and secondary amines, react well, afTording good to excellent yields of the desired products. Secondary amines generally react faster than primary amines in... 

Reports by the groups of Chan, Evans, and Lam in 1998 revealed an alternative method to conduct copper-mediated couplings that form C(aryl)-0 and C(aryl)-N bonds. In this process, arylboronic acids react with compounds containing N-H or 0-H bonds in the presence of a Cu(II) reagent or catalyst. TTiese reactions were initially conducted with stoichiometric amounts of copper reagents. " Amines, anilines, amides, ureas, carbamates, and sulfonamides underwent N-arylation in moderate to excellent yields by this process (Equation 19.124). The commercial availability of boronic acids and the ability to conduct these arylations in air under mild conditions has caused this method to be adopted quickly for synthetic applications on a small scale. 

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