Alkynyl carbamates

In recent years, Hoppe s group has considerably extended the isomerization-addition methodology, especially for the highly regio- and stereoselective synthesis of 1,2-alkadienyl carbamates. It involves deprotonation of alkynyl carbamates, transme-talation into a titanium species and subsequent reaction with carbonyl compounds [26-30]. This group recently described the preparation of enantiomerically enriched 4-hydroxyallenyl carbamates 22 by sparteine-mediated lithiation of alkynyl carbamates 20 [29]. Impressive examples of these transformations are summarized in Scheme 8.8. 

Hoppe and Gonschorrek also reported the interesting formation of an enyne structure [137]. Deprotonation of allenyl carbamates 242 bearing a benzoyloxy group caused a 1,4-elimination of lithium benzoate, furnishing 1-alkynyl carbamates 243 in moderate to good yield (Scheme 8.63). 

Various functionalized alkynes can be submitted to carbocupration reactions, such as alkoxyalkynes,150 alkynyl carbamates,151 acetylenic orthoesters,152 and thioalkynes.153 The carbocupration of orthoesters, for example, 204, has been used to prepare a-substituted esters of the type 206 by acidic hydrolysis of the adduct 205 (Scheme 51).152 This allows the formation of regioisomers that are not accessible by copper-mediated addition to acetylenic esters. A stereoselective synthesis of trisubstituted alkenes has been described by Normant et al.lSd> starting from phenylthio-acetylene 207. Carbocupration with lithium di- -butylcuprate affords the intermediate 208 which, upon addition of /z-butyllithium, undergoes a 1,2-metalate rearrangement to the vinylcuprate 209. The latter can be trapped with various electrophiles, for example, ethyl propiolate, providing product 210 with complete regio- and stereocontrol. 

The mechanism can be rationalized as follows (Scheme 76). Palladium iodide triggers the carbonylation of the propargyl amine to give an 2-alkynyl carbamate-Pd-iodide complex that inserts the triple bond to give a syn-vinyl-... 

Pd species. This intermediate undergoes carbonylation, methoxy substitution, and reductive elimination to furnish the Z-configured derivative 193. The resulting Pd(0)-species is reoxidized by oxygen in the presence of iodide ions. On the other hand, the presence of potassium iodide can also equilibrate the ( 2-alkynyl carbamate-Pd-iodide complex to the r/2-alkynyl carbamate-Pd-diiodide complex, which, in turn, causes an anti-attack of the carbamate at the Pdl2-complexed alkyne. Therefore, an antz-vinyl-Pd species results, which ultimately and accordingly leads to the -configured derivative 194. Without carbon monoxide the vinyl-Pd-species suffer a hydro-demetallation. 

Metal-catalysed cyclization is an increasingly important method of synthesis (reviews [B-4I, 2998, 3069, 3501, 3505 ). Bis(acetonitrile)dichloropalladium promotes cyclization of an alkynyl carbamate with epoxypropane and a vinyl chloride [3438] an alkynylaniline is converted into an indole by heating with a palladium chloride-triphenylphosphine catalyst [3631]. Mercury(II) acetate is an effective promotor of the cyclization of the alkenylaniline (37.2) to a reduced carbazole [3861]. 

Alkynyl(phenyl)iodonium salts have found synthetic application for the preparation of various substituted alkynes by the reaction with appropriate nucleophiles, such as enolate anions [980,981], selenide and telluride anions [982-984], dialkylphosphonate anions [985], benzotriazolate anion [986], imidazolate anion [987], N-functionalized amide anions [988-990] and transition metal complexes [991-993]. Scheme 3.291 shows several representative reactions the preparation of Ai-alkynyl carbamates 733 by alkynylation of carbamates 732 using alkynyliodonium triflates 731 [989], synthesis of ynamides 735 by the alkyny-lation/desilylation of tosylanilides 734 using trimethylsilylethynyl(phenyl)iodonium triflate [990] and the preparation of Ir(III) a-acetylide complex 737 by the alkynylation of Vaska s complex 736 [991]. 

With the assembly of the appropriate alkynyl carbamate, Takemoto has shown that Au(I)-catalyzed hydrocarbamation can be used in a tandem reaction approach to prepare nitidine (Scheme 15.125) [373]. Using the bulkier Buchwald-type mon-odentate biphenyl phosphine ligand, G-endo hydroamination products could be formed preferentially over the 5-exo products. 

Hashmi et al. reported that 7V-alkynyl carbamates underwent 1-catalyzed 5-endo-digcyclizdXion, yielding oxazolinones. In this case, the nitrogen was substituted with another EWG in addition to the Boc moiety due to the need in substrate preparation and perhaps attenuating the reactivity of the ynamide moiety (eq 12). ... 

The most salient commonality among the 210 carcinogens that are positive in Salmonella is the electrophilicity that is intrinsic to the molecule or introduced by enzymatic modification. The former can be thought of as ultimate mutagens and include known or presumable alkylating and acylating agents diazo compounds, nitrosamides, nitrosoureas, dimethylcarbamyl chloride, diaryl alkynyl carbamates, aziridines, oxiranes, thiirane,... 

The organolithium intermediate can also react intramolecularly [340] as exemplified by the intramolecular anti-selective 5-exo-dig carbolithiation of a-lithiated cy-carbamoyloxy-l-alkynyl carbamates for the synthesis of highly enantio-enriched protected 2-alkylidene-cycloalkane-l,3-diols [341] (Scheme 6.40). 

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