Metalation carbamates

D. Hoppe. O. Zschage, Chiral Metallated Carbamates.- Tools for New Strategies in A.symmetric Synthesis in Organic Synthesis via Organometallics, K. H. Dotz. R. W. Hoffmann, Eds., pp 267-284, Vieweg, Braunschweig 1990. 

Configurational stability has also been confirmed for various metalated carbamates by Hoppe and coworkers. Remarkably, carbamate-protected alcohols such as 20 are deprotonated enantioselectively, when treated with i-butyllithium in the presence of (—)-sparteine. The lithium carbenoids like 21 (R = alkyl) thus generated turn out to retain their configuration (equation 11). Similar results have been obtained for a-lithiated amines and carbamate protected amines " . As a rule, dipole stabilization of the organolithium compounds in general also enhances the configurational stability of a-oxygen-substituted lithium carbenoids. 

The highly selective abstraction of one of the enantiotopic protons in carbamates due to the presence of (—)-sparteine dnring the metalation step, onthned in equation 11, proved itself to be a particularly fruitful concept in the context of chiral economy Thus the protocol permits one to convert a prochiral snbstrate into a non-racemic product in remarkable enantioselectivity. Usually, metalated carbamates like 21 generated by this method react with electrophiles under retention of confignration (eqnation 70). In the metalation step, mediated by (—)-sparteine, the pro-5 proton is removed predominantly, and reaction products 169 are obtained in >95% ee as a rnle (eqnation 70) . ... 

The role that metalated carbamates play in synthesis is pointed out in equation 71 As they can be considered as protected alcohols, they serve as equivalents of alkanol d synthons 176. Starting from prochiral carbinols, an alkylation is feasible in a highly enantioselective manner. 

The possibility of insertion of C02 into metal-amide bonds via a mechanism not unlike S02 insertion into metal-alkyl bonds remains a viable possibility in C02 chemistry although it was not realized in these studies by Chisholm and co-workers. In this mechanism, C02 acting as an electrophile, attacks an amide nitrogen, with the intermediate then rearranging to the metal carbamate, (68). 

In natural processes, metal ions are often in high oxidation states (2 or 3), whereas in chemical systems the metals are in low oxidation states (0 or 1). This fact inverts the role of the metal center, such that it acts as a one-electron sink in a natural system, but as a nucleophile in an artificial ones (see other chapters of this book and the review by Aresta et al. [109]). Nevertheless, important biochemical processes such as the reversible enzymatic hydration of C02, or the formation of metal carbamates, may serve as natural models for many synthetic purposes. Starting from the properties of carbonic anhydrase (a zinc metalloenzyme that performs the activation of C02), Schenk et al. proposed a review [110] of perspectives to build biomimetic chemical catalysts by means of high-level DFT or ah initio calculations for both the gas phase and in the condensed state. The fixation of C02 by Zn(II) complexes to undergo the hydration of C02 (Figure 4.17) the use of Cr, Co, or Zn complexes as catalysts for the coordination-insertion reaction of C02 with epoxides and the theoretical aspects of carbamate synthesis, especially for the formation of Mg2+ and Li+ carbamates, are discussed in the review of Schenk... 

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] ... 

Despite the great number of metal-carbamates isolated to date, the transfer of a carbamic group from a metal center to an alkylating agent such as an alkyl halide or diatkyl sulfate has been documented in only a few cases [1, 2]. 

The transfer of carbamate groups from metal carbamates to acylating agents, such as acyl halides and chloroformates, has been extensively studied by Calderazzo and coworkers. 

Scheme 6.6 Reaction of metal carbamates with acylating agents a plausible route to isocyanate.

The transfer of a carbamate moiety to epoxides is a suitable entry into carbamic esters of 1,2-diols. Yoshida and Inoue reported tbat tbe reaction of Ti(NMe2)4 with C02 and 1,2-epoxycyclohexane, followed by hydrolysis of the reaction mixture, afforded tra s-2-hydroxycyclohexyl N,N-dimethylcarbamate [77a], This reaction was the first example of transfer of a carbamate group from a metal carbamate to an epoxide (Scheme 6.13). 

Scheme 6.13 Transfer of carbamate group from a metal carbamate to epoxides.

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. 

Studies of the polymerisation of alanine A-carboxylic acid anhydride with diethylzinc or triisobutylaluminium as the catalyst have revealed the relatively fast deprotonation of the monomer NH group by the metal alkyl as the first reaction step. This reaction (easily detectable by evolution of the ethane or isobutane) produces A-metallated initiating species (substituted metal carbamates) which, however, are not monomeric but undergo association via metal-heteroatom coordination bonds [75,175]. 

Reductive cleavage of Aloe groups can be accomplished under Pd 0)-catalysis using various hydride donors such as formic acid,190 tributylstannane,191 phenyl-silane,192 sodium borohydride193 or various borane-amine complexes.194 The reaction gives metal carbamate derivatives and propene as the primary products With tributylstannane the reaction is usually conducted in the presence of acetic... 

The total synthesis of amaryllidaceae alkaloid buflavin was achieved in the laboratory of A. Couture by utilizing a Horner-Wittig reaction between a biaryl aldehyde and a metalated carbamate. The diphenyl phosphine oxide carbamate was deprotonated with n-BuLi. To the resulting metalated carbamate was added the solution of the biaryl aldehyde in THF. The reaction afforded the corresponding (Z)- and ( )-enecarbamates in good yield and with high -selectivity. 

A solution of both ammonium pyrrolidinedithiocarbamate and diethyldithio-carbamate has been used for eomplexing iron (Co, Ni, Cu, Zn, Cd, Pb) in sea water. The metal carbamate complexes are extracted from 500 ml of sea water at ca. pH 5 into 30 ml of Freon TF (l,l,2-trichloro-l,2,2-trifluoroethane) and back-extracted into 10 ml of 0.3 M nitric acid. The main advantage of this method is the transfer of the metals to a solution in which their concentrations do not change with time 70). 

Hoppe D, Zschage O (1990) Chiral metallated carbamates Tools for new strategies in asymmetric synthesis. In Dotz KH, Hoffmann RW (eds) Organic synthesis via organo-metallics, 1st edn. Vieweg, Braunschweig, p 267... 

Aresta M, Dibenedetto A, Quaranta E (1995) Reaction of alkali-metal tetraphenylborates with amines in the presence of CO2 a new easy way to aliphatic and aromatic alkali-metal carbamates. J Chem Soc Dalton Trans 3359-3363... 

Aresta M, Quaranta E (1992) Alkali-metal-assisted transfer of carbamate group from phosphocarbamates to alkyl halides a new easy way to alkali-metal carbamates and to carbamate esters. J Chem Soc Dalton Trans 1893-1898... 

Chisolm [85-87] has extensively studied the reactirai of CO2 with amides of early transitimi metals to give metal carbamates (4.21). Insertion of the heterocumulene into the metal-amido bond (4.21)... 

As shown in Scheme 4.15, this reaction pathway has been largely exploited from the synthetic point of view for the preparation of a great number of metal carbamate... 

The aptitude of metal-amides and metal-carbamates to hydrolyze in the presence of adventitious water, as well as the occurrence of (4.22a), are major caveats in studying the mechanistic aspects of this insertion reaction [109] and the mechanism summarized by (4.22a) and (4.23) may also be working in other cases. However, CO2 attack oti metal bonded nitrogen is also possible and has been documented experimentally. 

However, CO2 can react with metal-imido bonds through a [2+2] cycloaddition reaction to give N,0-bound metal carbamates [118]. The latter species can react further and either extrude the corresponding isocyanate with formation of a metal-0x0 complex [83, 119] or also insert a second CO2... 

As already emphasized for transition metal carbamates, the O2C-N bond of the carbamate moiety of these systems is somewhat labile, and the carbamate group undergoes CO2 exchange processes easily. 

Some compounds retard oxidation entering simultaneously into several reactions. For example, they react with both alkyl and peroxyl radicals (anthracene, methyl-enequinone), decompose hydroperoxides, and terminate chains in the reaction with RO 2 (metal carbamates and thiophosphates). Such compounds are inhibitors of com-... 

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