Isocyanates with alkynes

Reactions involving the [4 + 1 + 1] principle, an example of which is shown in equation (136), are rather uncommon and of strictly limited utility [3 + 2 + 1] and [2 + 2 + 2] processes, on th,e other hand, are well known. Representative [3 + 2+1] three-bond formation processes are given in equations (137)—(141), from which it can be seen that the common situation is where ammonia, a substituted amine or formamide constitutes the one-atom fragment. Many [2 + 2 + 2] atom fragment syntheses are known and some are familiar reactions. Thus, the cobalt(I)-catalyzed condensation of nitriles and isocyanates with alkynes gives pyridines and 2-pyridones, often in excellent yield (e.g. equation 142), while the cyclotrimerizations of nitriles, imidates, isocyanates, etc., are well established procedures for the synthesis of 1,3,5-triazine derivatives (e.g. equation 143). Further representative examples are given in equations (144)-(147), and the reader is referred to the monograph chapters for full discussion of these and other [2 + 2 + 2] processes. Examination of the... 

The formal [2+2+1] cocyclization of alkenes, alkynes and CO by transition metal complexes has been used as a powerM tool for the synthesis of cyclopentenones (Scheme 10.1a) [15]. Other variants of C=C bond like allene, carbonyl or imino moiety can also be used in place of alkene or as a partner of alkene to synthesize 4-or 5-alkylidene cyclopentenones, [16] y-lactones [17] or y-lactams, [18] respectively. Catalytic [2+2+1] cocyclization can also be used with full efficiency to construct heterocyclic compounds using het-erocumulenic compounds such as carbodiimides and/or isocyanates with alkynes and CO (Scheme 10.1c). 

The 4-hydroxy-THISs react with electron-deficient alkynes to give cycloadducts (3) that spontaneously eliminate sulfur, producing 2-pyridones (3). Bulky 5-substituents lead to a decrease in the addition rate, and elimination of isocyanate with formation of thiophenes becomes favored (3, 12, 13). Benzyne yields an isolable adduct that exclusively extrudes isocyanate on thermolysis, but sulfur on irradiation (Scheme 7)... 

In a manner analogous to classic nitrile iinines, the additions of trifluoro-methylacetonitrile phenylimine occur regiospecifically with activated terminal alkenes but less selectively with alkynes [39], The nitnle imine reacts with both dimethyl fumarate and dimethyl maleate m moderate yields to give exclusively the trans product, presumably via epimenzation of the labile H at position 4 [40] (equation 42) The nitrile imine exhibits exo selectivities in its reactions with norbornene and norbornadiene, which are similar to those seen for the nitrile oxide [37], and even greater reactivity with enolates than that of the nitnle oxide [38, 41], Reactions of trifluoroacetomtrile phenyl imine with isocyanates, isothiocyanates, and carbodiimides are also reported [42]... 

The cobalt(I)-catalyzed condensation of nitriles (1 mole) or isocyanates (1 mole) with alkynes (2 moles) gives pyridines and 2-pyridones, often in excellent yield (Scheme 72). 

Diaryl-1,2,3,5-oxathiadiazines (277 from sulfur trioxide and aryl isocyanates) with (3-diketones yield pyrimidines (278). s-Triazine reacts with RCH2CN to give 4-aminopyrimidines (279 see Section 3.2.1.6.1 for a similar reaction), and with electron-rich alkenes and alkynes to yield pyrimidines such as (280) from EtC = CMe (Section 3.2.1.10.2). 

Fusion of a thiazole to pyrimidine betaines does not change the tendency of the latter for cycloaddition reactions, e.g. (306) forms adducts with alkynes (73JHC487). Similarly 1,3-thiazine betaines (399) react as 1,4-dipoles with aryl isocyanate with elimination of COS to produce pyrimidine betaines (400) (76CB3668). 

A Ni°-based system related to those already described in connection with syntheses of both cyclobut-enediones and several five-membered heterocycles (Sections 9.4.2.1, 9.4.3.3 and 9.4.3.5) is also capable of catalyzing pyridone synthesis from isocyanates and alkynes. However, the structures found for the isolable metallacyclic intennediates in this system imply a completely different insertion sequence isocyanate first, followed by the two alkynes (Scheme 35). As a consequence, the regiochemistry found in the products of reaction of unsymmetrical alkynes is the reverse of that typical of Co larger substituents end up at positions 4 and 6. Thus, starting wiA the carbonyl carbon of the isocyanate, each carbon-caib-on bond forming event is strongly regioselective for the less-hindered alkyne caibon (equation 46). The... 

Nickel(O) complexes undergo oxidative addition reactions with alkynes to give nickelacyclopentadienes and also react under certain conditions with carbon dioxide or isocyanates to form oxanickelacyclopentenones (87) " or azanickelacyclopentenones (88) (Scheme 30). In both cases the chelating basic ligand TMEDA (tetramethylethylenediamine) influences the reaction strongly. 

This behaviour correponds to the observation that other unsaturated hydrocarbons, e.g. alkynes, allenes or 1,3-butadienes, which readily undergo transition metal catalyzed cyclooligomerizations, do also incorporate CX multiple bonds in such cycloadditions only with difficulty in most cases 207 208). Besides the well known cobalt-catalyzed pyridin synthesis from alkynes and nitriles98 cocyclooligomerizations have been achieved with alkynes on one side and isocyanates 209), carbodiimides210) and carbondioxide 211) on the other side as well as with 1,3-butadienes and aldehydes 212), carbondioxide213 and 2-aza- or 2,3-diaza- 1,3-butadiene214. ... 

Many examples of alkene and alkyne insertion into metal-carbon bonds can also be found in the section on homogeneous catalysis. Other recent examples include the insertion of conjugated dienes into palladium-allyl bonds, olefin arylation in the presence of palladium acetate, and the reaction of ethylene with arylmagnesium halides in the presence of nickel chloride. Reaction of isocyanates with nickel-ethynyl compounds... 

The bis-alkyne side chain was synthesized as outlined in Scheme 64. Hy-drazone 300 was alkylated, followed by hydrolysis, to give a-hydroxy ketone 301, which was converted to oxazolone by treatment with trichloroacetyl isocyanate. The oxazolyl triflate 302, prepared by reaction of the oxazolone with triflic anhydride, was coupled with alkyne 213 under Sonogashira conditions as reported by Panek [118], followed by deprotection of MPM and oxidation, to furnish the side chain precursor bisalkynyloxazole 299. 

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