Isocyanates, reaction with alkynes

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. 

Thus the simplest aliphatic monomeric nitrone (369) has been studied in its reactions with alkynes and isocyanates. Problems were encountered since the nitrone was found to be in the form of an adduct (370) with excess pivaldehyde, although it is possible to remove the aldehyde in vacuo at the melting point. The simple products of cycloaddition (371) and (372) were isolated in good yield. 

The 1,3-dipolar character of triazaallenium salts, from now on referred to as l,3-diaza-2-azoniaallene salts, is evidenced by the many [3+2] cycloaddition reactions these types of compounds can participate in. The l,3-diaza-2-azoniaallene salts are generated in situ and trapped with suitable dipolarophiles. For example, l,3-diaza-2-azoniaallene salts undergo stereospecific [3+2] cycloaddition reactions with alkynes and olefins. However, they fail to react with isocyanates, isothiocyanates and azo compounds. Also, [3+2] cycloadditions to carbodiimides and cyanamides are observed. In contrast, nitriles fail to react. 1,3-Diaza-2-azoniaallene salts are obtained in the oxidation of 1,3-disubstituted triazenes with t-butyl hypochlorite. The resultant Al-chlorotriazenes react with antimony pentachloride to form the salts as reactive intermediates. Above —25°C, l,3-diaza-2-azoniaaUene salts disproportionate into diazonium salts and azo compounds. 

Methylarsine, trifluoromethylarsine, and bis(trifluoromethyl)arsine [371-74-4] C2HAsF, are gases at room temperature all other primary and secondary arsines are liquids or solids. These compounds are extremely sensitive to oxygen, and ia some cases are spontaneously inflammable ia air (45). They readily undergo addition reactions with alkenes (51), alkynes (52), aldehydes (qv) (53), ketones (qv) (54), isocyanates (55), and a2o compounds (56). They also react with diborane (43) and a variety of other Lewis acids. Alkyl haUdes react with primary and secondary arsiaes to yield quaternary arsenic compounds (57). 

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]... 

M-substituted 2-pyridones can be prepared by N-alkylation, under basic conditions (pfCa of the amide proton is 11). The resulting anion can then react on either nitrogen or oxygen depending on the conditions employed [24-27]. Also, several direct methods for the construction of N-substituted 2-pyridones have been reported. Two such examples can be seen in Scheme 3 where the first example (a) is an intramolecular Dieckmann-type condensation [28] and the second (b) is a metal-mediated [2 -I- 2 + 2] reaction between alkynes with isocyanates [29,30]. 

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... 

Oxazin-4-ones and -thiazin-4-ones are well represented in the chemical literature. Thiazin-4-ones can be synthesized from 1,3-oxazinium salts by the action of hydrogen sulfide and potassium carbonate (81H(15)85l) and oxazin-4-ones are obtained by cycloadditions between isocyanates and ketenes (Scheme 73), or alkynes (Scheme 74), or between nitriles and acylketenes (Scheme 75). Similarly diketene is often used and affords oxazin-4-ones by its reactions with imidates and cyanamides (Scheme 76) (80H(14)1333>. 

Thiobenzoyl isocyanate is widely used as a starting material for the syntheses of TAs 23-28 both in condensation with ethyl sodiocyanoacetate (86KGS3) and in [4 + 2]-cycloaddition reactions with alkenes and alkynes containing electron-donor groups (81CB2713 85ZC324) (Scheme 4). It is established that the rate of cycloaddition increases from alkenes to alkynes and with the electron-donor properties of substituents. 

The mechanism of ring formation from monoalkyne and heterocumulenes, catalysed by Ni(0) complexes, Lx Ni(0), has been proposed to involve one-step cycloaddition scheme (10) [103] and scheme (11) [104, 105] show the formation of the 2-pyrone ring in the alkyne reaction with carbon dioxide and the 2-pyridone ring in the alkyne reaction with isocyanate respectively ... 

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). 

Sydnones can be regarded as cyclic azomethine imines and as such they undergo thermal cycloaddition reactions with a range of dipolarophiles. Thus, reaction with phenyl isocyanate converts 401 into 1,2,4-triazole 402. On photolysis, 3,4-diarylsydnones lose carbon dioxide and give nitrile imines, which can also be intercepted by dipolarophiles. Thermal reactions with acetylenic dipolarophiles lead to the formation of pyrazoles (Scheme 88) however, these reactions are rarely completely regioselective with unsymmetrical alkynes, e.g., <2000BKC761, 2000TL1687>. 

Coordinated alkyne and alkylidyne groups can form new C-C bonds by reactions with other compounds such as isocyanates (468), isocyanides (469), or by a reduction mechanism (470) (Fig. 43). 

Few reactions of alkynes with C—X bonds are valuable for the preparation of four-membered hetero-cycles. Ynatnines react with aldehydes and ketones in the presence of Lewis acids to give unstable oxetene derivatives which undergo electrocyclic opening (Scheme 43). Open-chain products are also obtained with thiocarbonyl compounds,Schiff bases and iminium salts. Reactions of ynamines with carbon dioxide, ketenes, - ketenimines and isocyanates " often give mixtures of products and are of little preparative value. 

Pyridones are accessible from formal [2 -i- 2 + 2] cycloaddition of two alkynes and an organic isocyanate. Two quite distinct catalyst systems have been developed for this reaction, with significant differences between them in mechanism and mechanistic implications on selectivity. 

Similarly, although the yields are lower, the Co catalysts also show generally reversed regioselectivity in reactions with carbodiinudes as compared with isocyanates. °- In fact, the 4,6-disubstituted product is formed with complete regioselectivity in reactions of di(p-tolyl)carbodiimide with terminal alkynes. 

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