Alcohols carbamate synthesis

A" 0-Butenolide, 46, 22 /-Butyl alcohol, in synthesis of phenyl /-butyl ether, 45, 89 reaction with sodium cyanate and trifluoroacetic acid, 48, 32 /-Butyl azidoacctatc, 46, 47 hydrogenation of, 45, 47 /-Butyl carbamate, 48,32 /-Butyl chloroacetate, reaction with sodium azide, 45, 47 /ra S-4-/-BuTYI,CYCLOHEXANOL, 47,16... 

Although numerous methods are known for the synthesis of carbamates of primary and secondary alcohols, they are not satisfactory for the preparation of carbamates of tertiary alcohols /-Butyl carbamate was first obtained by reaction of sodium /-butoxide with phosgene and tbionyl chloride at —60°, followed by reaction with concentrated aqueous ammonia, the overall yield was less than 20%. This procedure, however, was found to be unsuitable for the preparation of carbamates of other tertiary alcohols. Carbamates have been prepared by the... 

The nonphosgene production of isocyanates takes place through the thermolysis of the corresponding carbamate. The carbamate synthesis may involve a number of possible alternative ways, such as the reaction of a nitrocompound with CO, or the reaction of an amine with CO and O2, with urea and alcohol, or with a carbonic ester. Among these routes, the reaction of DMC or DPC with aliphatic amines is a very efficient way to produce carbamates. 

Ono, K., Fugami, K., Tanaka, S. and Tamaru, Y. (1994) Palladium catalyzed arylation of IV-alkyl O-allylic carbamates synthesis of cinnamyl alcohols via Heck arylation. Tetrahedron Lett., 35, 4133-6. 

TABLE 5.7 Heterogeneous catalysts for carbamate synthesis from CO, amine and alkyl halide or alcohol. 

Allylsilanes are available by treatment of allyl acetates and allyl carbonates with silyl cuprates17-18, with antarafacial stereochemistry being observed for displacement of tertiary allyl acetates19. This reaction provides a useful asymmetric synthesis of allylsilanes using esters and carbamates derived from optically active secondary alcohols antarafacial stereochemistry is observed for the esters, and suprafacial stereochemistry for the carbamates20,21. 

Unfortunately, the presence of the benzylic alcohol moiety at the focal point of the dendrimer, along with the catalyst (used in the urethane formation) led to the formation of undesired side products, presumably due to carbamate interchange. These side reactions were avoided by switching to monomer 19, methyl-3,5-dihydroxybenzoate. While the carbamate linkages of dendrons 53 and 54 were too unstable under the alkylation conditions required to afford larger dendrons, the merits of the concept was adequately demonstrated for this accelerated synthesis of [G-3] dendrons. 

The direct conversion of alcohols and amines into carbamate esters by oxidative carbonylation is also an attractive process from an industrial point of view, since carbamates are useful intermediates for the production of polyurethanes. Many efforts have, therefore, been devoted to the development of efficient catalysts able to operate under relatively mild conditions. The reaction, when applied to amino alcohols, allows a convenient synthesis of cyclic urethanes. Several transition metal complexes, based on Pd [218— 239], Cu [240-242], Au [243,244], Os [245], Rh [237,238,246,247], Co [248], Mn [249], Ru [224,250-252], Pt [238] are able to promote the process. The formation of ureas, oxamates, or oxamides as byproducts can in some cases lower the selectivity towards carbamates. 

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. 

Ojima and coworkers have developed a similar approach to the synthesis of piperidine and related ring systems, which they describe as cyclohydrocarbonylation. In this approach, carbamate-protected allylglydnes (for example, 32) are subjected to rho-dium(I)-catalyzed hydroformylation in an alcohol solvent (Scheme 5.13) [17]. 6-Alkoxy-pipecolates 33 are isolated in good yield and were shown to be amenable to further stereoselective transformations. This methodology has recently been expanded to include fully intramolecular variants that can form two rings in a single reaction. Thus, alkenes 34 are subjected to the cyclohydrocarbonylation conditions to provide azabicy-clo[4.4.0]aUcane amino acids 35 which can serve as conformationaUy restricted dipeptide surrogates and /9-turn mimetics [18]. 

Intramolecular rhodium-catalyzed carbamate C-H insertion has broad utility for substrates fashioned from most 1° and 3° alcohols. As is typically observed, 3° and benzylic C-H bonds are favored over other C-H centers for amination of this type. Stereospecific oxidation of optically pure 3° units greatly facilitates the preparation of enantiomeric tetrasubstituted carbinolamines, and should find future applications in synthesis vide infra). Importantly, use of PhI(OAc)2 as a terminal oxidant for this process has enabled reactions with a class of starting materials (that is, 1° carbamates) for which iminoiodi-nane synthesis has not proven possible. Thus, by obviating the need for such reagents, substrate scope for this process and related aziridination reactions is significantly expanded vide infra). Looking forward, the versatility of this method for C-N bond formation will be advanced further with the advent of chiral catalysts for diastero- and enantio-controlled C-H insertion. In addition, new catalysts may increase the range of 2° alkanol-based carbamates that perform as viable substrates for this process. 

Af-Acyloxy-Al-alkoxyureas and carbamates (equation 9, R = NR2, RO) have been generated similarly in MeCN . Earlier, the same group described the synthesis of N,N-dialkoxyureas (76) from the reaction of Al-alkoxy-V-chloroureas (75) with sodium alkox-ides in the corresponding alcohol (equation 10) Properties of Af,Af-dialkoxyamides and -ureas and -carbamates are described in Section V. 

The synthesis of polyurethanes is usually presented as proceeding via the formation of carbamate (urethane) linkages by the reaction of isocyanates and alcohols ... 

The procedure reported here, which is that of Hassner and Heathcock,3 is more convenient than the Wenker synthesis of aziridines4 and appears to be more general.5 It represents a simple route from olefins to aziridines (via 8-iodo carbamates).356 Aziridines are also useful as intermediates in the synthesis of amino alcohols and heterocyclic systems.5,7-9... 

The original synthesis of duloxetine (3) is relatively straightforward, involving a four-step sequence from readily available 2-acetylthiophene 30 (Scheme 14.7). Understandably, the main synthetic challenge stems from the presence of a chiral center, because duloxetine (3) is marketed as the (5)-enantiomer as shown. Thus, a Mannich reaction between 30 and dimethylamine generated ketone amine 31, which was then reduced to provide intermediate racemic alcohol amine 32. The desired optically active (5)-alcohol 32a was accessed via resolution of racemate 32 with (5)-(+)-mandelic acid, which provided the necessary substrate for etherihcation with 1-fluoronaphthalene to afford optically active amine 33. Finally, A -demethylation with 2,2,2-trichloroethyl chloroformate and cleavage of the intermediate carbamate with zinc powder and formic acid led to the desired target duloxetine (3). 

The carbamate derivatives of amino alcohols also proved applicable for the synthesis of cyclic hemiaminal derivatives. Through the ring closures of W-BOC-substituted 1,3-amino alcohols with aldehydes or acetals, 3-BOC-1,3-oxazine derivatives were obtained <1998TL6561, 1999J(P1)1933, 2006JOC8481, 2006T8687, 2006TL7923>. 

The synthesis of the protected 5-hydroxy P-amino acids 91 required a stereoselective amination of the vinyl sulfoximine 4 (Scheme 1.3.29). Carbamoylation of alcohols 4 with trichloroacetyl isocyanate afforded carbamates 86 in high yields. 

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