Directivity carbamate group

The strongly directing carbamate group allows for the presence of remote sty-ryl or phenylethynyl groups during the enantioselective deprotonation step of the substrate. The phenyl group activates the double or triple bond for an intramolecular carbolithiation [109]. Since carbolithiation is the topic of Chapter 9, only few representative ideas and examples are discussed briefly below. 

It has been proposed dial a directed cuprate addilioti widi a carbamate or a carbonate serving as a reagenl-directing functional group may account for die stereo-clieniical outcome of diese reactions fsee models 115 and 116 in Sclieme 6.25) [39,... 

Other examples of intramolecularly coordinated (by 0 as well as by N groups) organolithium compounds can be found in Setzer and Schleyer (2) and Seebach (4). Two recent reviews are also pertinent. Klumpp (34) deals with 0- and N-assisted lithiation and carbolithiation of nonaromatic compounds, and Snieckus (34a) deals with directed (by amide and carbamate groups) ortho metalation in polysubstituted aromatics. 

The fixation of C02 by amines, which has been recognized for a long time, can either take place directly or it can be mediated by metal or nonmetal species to provide a carbamate group, RR NC02 , which is bound either ionic or covalently to an electrophilic center [1-5]. The direct interaction of C02 with primary or secondary amines can afford carbamic acids or alkylammonium carbamates (Equations 6.1 and 6.2) [1, 2], In the presence of metals, metal salts (Equation 6.3) [3j, k] or metal-complexes, metal carbamates can be obtained [3, 4] ... 

The reaction of metal N-alkylcarbamates M(C)2CN 11 R) (M = Na, Mn(II), Co(II) R = Ph, Pr, Cy) with R C(0)C1 (R = Me, Ph) takes place, at ambient temperature, in a more complex way with the formation of isocyanates (RNCO), carboxylic anhydrides (R C(0)0C(0)CR ), amides (RNHC(O)R ) and C02. Amide formation and the evolution of C02 can be due to (i) the decomposition of mixed anhydride RNHC(0)0C(0)R obtained by addition of the acyl chloride to the oxygen atom of the carbamate group or (ii) the direct reaction of acyl chloride at the carbamic nitrogen atom of M(02CNHR) . The mixed anhydride RNHC(O) 0C(0)R might also decompose via another route so as to afford isocyanate and carboxylic acid. However, a different pathway (Scheme 6.6) has been also envisaged for the formation of RNCO and R C(0)0C(0)CR, which excludes any intermediacy of the mixed anhydride [61a], Two acetic acid molecules, bound to the same metal or to different metal centers, would then be dehydrated and acetic... 

The simple compound 79 is an aggregation pheromone of the fruit fly Drosophila mulleri. Hoppe proposed to synthesise it by asymmetric deprotonation and retentive methylation of a carbamate derivative of n-dodecanol.8 Given that the carbamate group (required for directed oc-lithiation) must, at the end of the synthesis, be removed from the molecule, the best choice is the tetramethyloxazolidine-derived 81, readily formed by acylation with the carbamoyl chloride 80. Lithiation of 81 with excess s-BuLi-(-)-sparteine gives, by asymmetric deprotonation, a configurationally stable complex of organolithium 82 with (-)-sparteine. 

For direct liquid chromatography the native CDs are primarily immobilized via one or two primary hydroxyl groups, e.g. via a carbamate group onto a prefunctionalized silica... 

Product-ion MS-MS spectra of carbamates were investigated by Chiu et al. [24], using thermospray ionization and either protonated or ammoniated molecules as precursor ions. The fragmentation is similar to that in in-source CID. For A -methyl carbamates, the loss of 57 due to methyl isocyanate is a characteristic feature. In N-oxime carbamates, the fragmentation is directed from the oxime rather than from the carbamate group. 

Metallinos, C., Nerdinger, S., Snieckus, V. N-Cumyl Benzamide, Sulfonamide, and Aryl O-Carbamate Directed Metalation Groups. Mild Hydrolytic Lability for Facile Manipulation of Directed Ortho Metalation Derived Aromatics. Org. Lett. 1999, 1, 1183-1186. 

The stereochemical outcome for the Strecker reaction is rationalized by the reaction pathway described in Fig. (22). A preferred conformation of in situ generated imine 57 may be the one in which the bulky carbamate group directs toward cis to the hydrogen atom on the a-methine carbon of the imino group. TMSCN then attacks intramolecularly the Si face of 57 by means of activation through coordination of the imino group to the hypervalent silicon atom. This may result in the preferential formation of the syn isomer over the anti counterpart. 

Now comes the clever bit. Lithiation of 63 with LDA occurs next to Br at the only remaining free position 64 but the halogen dance (chapter 32) exchanges Br and Li so that Li is next to the excellent ortho-directing carbamate 65. Protonation with EtOH gives 66 ready for introduction of the fourth and last OH group. 

The introduction of a carbonyl carbamate group at position 4 of the pyrazol-3-one ring can be done directly by fusion of appropriately 2-substituted /i-keto ester with a hydrazine (04TJC659) (Scheme 16). The jS-keto ester 67 was synthesized in two steps from ethyl 4,5-dioxo-2-phenyl-4,5-dihydrofuran-3-carboxylate 65 by decarbonylation to ethoxy-carbonylbenzoylketene intermediate 66 in refluxing benzene and then nucleophilic addition by methyl carbamate. Ethyl 2-benzoyl-3-[(methoxy-carbonyl)amino]-3-oxopropanoate 67 with diphenylhydrazine on heating in benzene gave 4-substituted pyrazol-3-one 68 in 44% yield. 

The enzyme phosphotriesterase hydrolyzes many different organophosphorus triesters, including several acetylcholinesterase inhibitors. The chemical mechanism involves an activated water molecule that directly attacks the phosphorus center with a resultant inversion of configuration [708]. Thus the overall reaction mechanism does not involve the formation of a phosphorylated-enzyme intermediate, but it does involve a Schiff base-type interaction between carbon dioxide and a lysine residue giving a carbamate group in the active site. 

Directed lithiation of (9-aryl carbamates provides a method for the formation of 2-substituted phenols. For example, quenching with dimethylformamide (DMF) gave the aldehyde 130 (1.120). Interestingly, if no electrophile is added but the mixture is allowed to warm to room temperature, then a rearrangement takes place, in which the aryllithium species undergoes attack on the carbamate group (1.121). 

The discovery of the A-cumyl directed metalation group (DMG) for amides, 0-carbamates, and sulfonamides helps to broaden the scope of new DoM strategies. Synthetic utility is demonstrated by establishing viable routes to 4- and 4,7-substituted saccharin derivatives (eq 50). Thus, BuLi/TMEDA metalation of selected biaryl A -cumylsulfonamides followed by M(Y-diethylcarbamoyl chloride quench results in a regioselective functionalization (eq51). 

Cramer and co-workers reported a Ni-catalyzed asymmetric hydrocarbam-oylation reaction of alkenes with diaminophosphine oxide ligands. The acyl C—H bond of a carbamate group was directly functionalized. It is known that secondary phosphine oxides are usually air-stable and robust preligands because of their unique tautomerization between P and In the presence of bases or transition metals, such an equilibrium can be shifted to the trivalent phosphinous acid and thus provide the opportunity for hetero-bi-metallic catalysis where a late transition metal and an early transition metal can coordinate to the phosphorus atom and the oxygen atom, respectively (Scheme 8.17). 

To demonstrate the advantages associated with utihzing carbamates as crosscoupling partners, a synthetic application of the methodology was reported by Garg, Snieckus, and coworkers (Scheme 2.20) [68]. Thus, in this synthesis of di-substituted pyridine 108, the carbamate group of 105 was first used as a directing... 

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