Carbamates, methoxy, reaction with

The most important group of derivatives for the amino function (Fig. 7-4) is the carbamate group, which can be formed by reactions with acids, acid chlorides or acid anhydrides. A series of chlorides as 2-chloroisovalerylchloride [1], chrysanthe-moylchloride [2] and especially chloride compounds of terpene derivatives (cam-phanic acid chloride [3], camphor-10-sulfonyl chloride [4]) are used. The a-methoxy-a-trifluoromethylphenylacetic acid or the corresponding acid chloride introduced by Mosher in the 1970s are very useful reagents for the derivatization of amines and alcohols [5]. 

Crich and Rumthao reported a new synthesis of carbazomycin B using a benzeneselenol-catalyzed, stannane-mediated addition of an aryl radical to the functionalized iodocarbamate 835, followed by cyclization and dehydrogenative aromatization (622). The iodocarbamate 835 required for the key radical reaction was obtained from the nitrophenol 784 (609) (see Scheme 5.85). lodination of 784, followed by acetylation, afforded 3,4-dimethyl-6-iodo-2-methoxy-5-nitrophenyl acetate 834. Reduction of 834 with iron and ferric chloride in acetic acid, followed by reaction with methyl chloroformate, led to the iodocarbamate 835. Reaction of 835 and diphenyl diselenide in refluxing benzene with tributyltin hydride and azobisisobutyronitrile (AIBN) gave the adduct 836 in 40% yield, along with 8% of the recovered substrate and 12% of the deiodinated carbamate 837. Treatment of 836 with phenylselenenyl bromide in dichloromethane afforded the phenylselenenyltetrahydrocarbazole 838. Oxidative... 

The preformation of carbazol-9-ylpotassium (sodium) has been much less used for the introduction of acyl groups onto nitrogen examples are the formation of 9-methoxy- and 9-ethoxy-carbonylcarbazoles, the dithio-carbamate salt 51, and the malonate 52 by reaction with the alkoxy-chloroformates, carbon disulhde, and malonic acid half-acid chloride, respectively. 

Reaction of 9-fluoro-7-oxo-2,3-dihydro7H-pyrido[l,2,3-de][l,4]oxa-zine-6-carboxylate and ferf-butyl (2-mercaptoethyl)carbamate in DMSO at 100 °C for 5 h gave 9-[2-(ferc-butoxycarbonylamino)ethylthio] derivative (06WOP2006/050943). The iodo atom of 9-iodo-7-oxo-2,3-dihydro-7H-pyrido[l,2,3-de][l,4]oxazine-6-carboxylic acids was coupled with 4 -0-(2-allyloxyethyl)azithromicin in MeCONMe2 in the presence of Bu3N and fra s-di-g-acetato-bis[2-(di-o-tolylphosphino)benzyl]dipalladium(II) and di(ferf-butyl)-4-methylphenol at 110-115 °C for 15-17 h to give a mixture of 9-(3-substituted prop-1- and -2-enyl) derivatives (07WOP2007/ 054296). 10-methoxy and 10-cyano-3-hydroxymethyl-2,3-dihydro-5H-pyr-ido[l,2,3-de][l,4]benzoxazin-5-ones were obtained from 10-bromo derivative by reaction with NaOMe in the presence of Cu(I)I at 140 °C in DMF,... 

In one approach, an imine moiety was generated in situ by reaction of a methoxy carbamate with lithium diisopropylamide. This imine was then condensed with an ester enolate to give the amino-ester, protected as a carbamate. Reaction of 4,70 with lithium diisopropylamide gave imine 4.71, for example. Subsequent reaction with... 

The titanium- ate complexes of a-methoxy allylic phosphine oxides, generated in situ by reaction of the corresponding lithium anion and Ti(0-i-Pr)4, condense with aldehydes exclusively at the a-position to produce homoallylic alcohols in a diastereose-lective fashion. The overall result is the three-carbon homologation of the original aldehyde, and this protocol has been used in a synthesis of (-)-aplysin-20 from nerolidol. The titanium- ate complex produced by reaction of the chiral lithium anion of an ( )-crotyl carbamate with Ti(0- -Pr)4 affords -y-condensation products (homoaldols) on reaction with aldehydes. Allyl anions produced by the reductive metalation of allyl phenyl sulfides condense with a,p-unsaturated aldehydes in a 1,2-manner at the more substituted (a) allyl terminus in the presence of Ti(0-i-Pr)4. 1,2-Addition of dialky Izincs to a,p-unsaturated aldehydes can be achieved with useful levels of enantiocontrol when the reaction is conducted using a chiral titanium(IV) catalyst in the presence of Ti(0- -Pr)4 (eq 20). Higher ee values are observed when an a-substituent (e.g. bromine) is attached to the substrate aldehyde, but a -substituent cis-related to the carbonyl group has the opposite effect. 

The cyclic carbamate (oxazoIidin-2-one) 313 is formed by the reaction of phenyl isocyanate (312) with vinyloxirane[I92]. Nitrogen serves as a nucleophile and attacks the carbon vicinal to the oxygen exclusively. The thermodynamically less stable Z-isomer 315 was obtained as a major product (10 I) by the reaction of 2-methoxy-l-naphthyI isocyanate (314) with a vinyloxir-... 

The synthons of oxiranes have also been used in this respect. For example, the reaction of C02 with a-bromoacylophenones in the presence of aliphatic primary amines, in methanol, afforded 3-alkyl-4-hydroxyoxazolidin-2-one derivatives under mild conditions [83a]. However, neither oc-bromoacetophenone nor a-chloroacetophenone afforded any carbamate product, and no urethanes were obtained with aromatic or aliphatic secondary amines. The proposed mechanism involved, as the first step, the formation of a 3-alkyl-2-methoxy-2-phenyloxirane intermediate, which reacted with alkylammonium carbamate to give the oxazo-lidone product (Scheme 6.16). This synthetic protocol was successfully applied to the synthesis of bis(oxazolidin-2-one) derivatives by reactions of 2-methoxy-3,3-dimethyl-2-phenyloxirane or a-bromoisobutyrophenone with C02 and aliphatic a,G)-diamines [83b],... 

In general, benzimidazole-2-methyl carbamate derivatives (28) can be synthesized by the reaction of an appropriate diamine (26) with 1,3-dicarbo-methoxy-5-methylisothiourea (27) [43], This is the most general and economic synthesis for benzimidazole carbamates. However, the same reaction was less than satisfactory when the aza analogues of o-phenylenediamines (29) were used. In order to synthesize the aza analogues of mebendazole (2) or flubendazole (3), the reactions of methoxycarbonyl isothiocyanate (30) with a wide variety of diamines such as 3,4-diaminopyridines, 4,5-diaminopyrimi-dines, o-phenylenediamines have been investigated in the presence of dicyclo-hexylcarbodiimide [44, 45] and were found to be quite successful in the synthesis of carbamates (31). 

In addition to the regiocontrol, the use of SMA carbamates provides activation to the reaction through overlapping of the lone-pair electrons on the nitrogen with the s-orbital of the C-Si bond.96 In this process, the trimethylsilyl group is replaced by a methoxy group. In fact any nucleophile can be used. Thus, various carbanions were utilized for the synthesis of spiro compounds that are synthons, for example, in an excellent route to cephalotaxine.354... 

This same methoxy—methyl combination reaction was used as a reference in deriving the absolute kinetic parameters of the reactions of methoxy with methyl formate [192], methyl acetate [367] and dimethyl carbamate [368] (Table 33). 

Kumar and coworkers have reported preparation of 2, 3 -epimino analogues of the antibiotics neamine, ribostamine, and kanamycin B by reaction of suitably protected vicinal benzyloxycarbonylamino tosylates with NaH in N,N-dimethylformamide, followed by deprotection. lodo-carbamates 119 and 120 were obtained by addition of iodine isocyanate to 2-methoxy-4,6-dimethyl-3, 6-dihydro-2/f-pyrane 118 (a mixture of cis and trans isomers), followed by treatment with MeOH. Treatment of compound 119 and 120 with potassium hydroxide in refluxing methanol afforded epimines 121 and 122. 

This reaction was first reported by Riemschneider in 1949. It is an acidic transformation of alkyl or aryl thiocyanates into thiocarbamates and is known as the Riemschneider reaction. In this reaction, when thiocyanates are treated with concentrated sulfuric acid, the corresponding thiocarbamates are obtained. In parallel, when thiocyanates are treated with concentrated sulfuric acid in the presence of alcohol or olefin, the corresponding A -substituted carbamates are yielded. The alcohols or olefins that are stable in the presence of sulfuric acid, including isopropyl alcohol, cc-butyl alcohol, r-butyl alcohol, cyclohex-anol, isobutylene, and camphene aU are suitable for this reaction, whereas low-order alcohols such as methanol and ethanol do not react with thiocyanate to give the corresponding A -substituted thiocarbamates. hi addition, the benzyl thiocyante and some ortho-substituted phenyl thiocyanates cannot be transformed into the corresponding thiocarbamates under these conditions because they are sensitive to sulfuric acid. Some unsuitable thiocyanates are o-carboxyl, o-methoxy, o-nitrophenyl thiocyanates, and o-methyM-amino phenyl thiocyanate. ... 

Reaction of 2 methoxy 4"propenyl phenyl methyl carbamate, 11, with... 

Reaction of 2-methoxy-4-propenyl phenyl methyl carbamate, 11, with 4-pheny1-1,2,4-triazoline-3,5-dione, 1. A 100 ml round-bottomed flask was charged with 1.58 g (9.04 x 10 mole) of I and 40 ml of CH2CI2. The red solution was cooled in an ice bath with stirring. To this red solution, a... 

An interesting acid surrogate is oxazolidine 4.90 (developed by Meyers), which reacted with methoxy carbamate 4.70 (see section 4.3.B.U) in the presence of lithium diisopropylamide and TiCl(OiPr)3 to give 4.91 - Acid hydrolysis converted 4.91 to an acid and esterification gave methyl 3-(N-methylcarbamoyl)-4-methylpentanoate, 4,92 (90% ee, R see chapter five for other enantioselective reactions). In addition, the 3-aminobutanoate derivative was prepared by this method, as was the 3-amino-hex-5-enoic acid derivative. 

In reaction 27 (Ar = 3,4-diclorophenyl), no carbamate was formed at room temperature and pressure but, when the reaction was conducted by injecting complex (J) (Ar = Ph) into an autoclave containing a THF-MeOH solution preheated at 200 and under 60 atm CO, carbamate was formed along with aniline. This behaviour is consistent with the aforementioned competition between dehydrogenation of the coordinated methoxy group and CO insertion. In the first case, some aniline is formed which is not later carbonylated and so accumulates in solution. In the second, the aniline initially formed can further react with the methoxycarbonyl complex to afford carbamate (or isocyanate, if the mechanism proceeds analogously to the one found for Ru(CO)3(DPPE)). 

The reaction between ethyl Hthiopropiolate and the N-acylpyridinium salt formed by reaction of 4-methoxy-3-methyl-5-(triisopropylsilyl)pyridine 2363 with (+)-frafis-2-(a-cumyl)-cyclohexyl chloroformate (TCC chloro-formate) was the starting point in the synthesis of (-l-)-aUopumihotoxin 267A (1718) by Comins et al. (Scheme 301). The dihydropyridone product (—)- 2364 was obtained diastereoselectively (>96%) before hydrogenation to the saturated ester (+)-2365. However, some epimerization of the methyl substituent was apparent after cleavage of the TCC carbamate with lithium methoxide and cyclization to the indolizidinone (—)-2366 (dr 8 1). Acetoxylation at C-8 with lead tetraacetate was stereoselective, and introduced the acetate from the axial direction, possibly by stereoelec-tronicaUy-controUed intramolecular transfer of acetate from a lead—enol intermediate. The acetoxy product (—)-2367 was protodesilylated with formic acid, after which a one-pot tandem reduction with K-Selectride followed by hthium aluminum hydride gave diol (- -)-2368 with complete... 

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