Isocyanates, reaction with allenes

Four-membered heterocycles are easily formed via [2-I-2] cycloaddition reac tions [65] These cycloaddmon reactions normally represent multistep processes with dipolar or biradical intermediates The fact that heterocumulenes, like isocyanates, react with electron-deficient C=X systems is well-known [116] Via this route, (1 lactones are formed on addition of ketene derivatives to hexafluoroacetone [117, 118] The presence of a trifluoromethyl group adjacent to the C=N bond in quinoxalines, 1,4-benzoxazin-2-ones, l,2,4-triazm-5-ones, and l,2,4-tnazin-3,5-diones accelerates [2-I-2] photocycloaddition processes with ketenes and allenes [106] to yield the corresponding azetidine derivatives Starting from olefins, fluonnaied oxetanes are formed thermally and photochemically [119, 120] The reaction of 5//-l,2-azaphospholes with fluonnated ketones leads to [2-i-2j cycloadducts [121] (equation 27)... 

The 1,2-functionalization of the allene moiety in 2-azetidinone-tethered alleny-nol derivatives has also been explored [96]. Carbamate 174 was selected as the starting material for the palladium(II)-catalyzed reaction. The above carbamate was prepared from the ot-allenic alcohol 171a by treatment with tosyl isocyanate. Reaction of compound 174 was carried out at room temperature in acetonitrile in the presence of 10 mol% of Pd(OAc)2, 5 equiv of LiBr, 2 equiv of Cu(OAc)2 and 1.2 equiv of K2CO3 under an atmospheric pressure of oxygen. The 1H-XMR spectrum of the crude material displayed neither signal corresponding to the allene... 

The reaction between isocyanic acid and allenes was also studied and showed different regiochemistries depending on the substitution pattern (Scheme 35). Thus, in the simplest case (not studied experimentally), the formation of the 4-substituted cycloadduct (141) is predicted to be strongly favored, mainly because of the lower distortion of the allenic moiety at the transition structure (140). In contrast, substituted allenes such as 1,3-dimethylallene form the 3-alkylidene derivative (143) via a more stabilized transition structure like (142), in good agreement with the experimentally observed regiochemistry[113-115]. 

Dobrowolski and co-workers reported calculations of the thermodynamic stability of the products derived from cycloaddition of vinylimine and ketene and of isocyanic acid and allene using MP2, density functional theory (DFT) (B3PW91), and Hartree-Fock (HF) methods with the 6-311+- -G basis set. Fourteen different structures were calculated for these cycloaddition reactions and the values of the free Gibbs energy showed that only 4- and 3-methylene-/3-lactams could be formed in considerable amount. 

Menthol [(—)-l] has been used as a chiral ligand for aluminum in Lewis acid catalyzed Diels-Alder reactions with surprising success2 (Section D.l.6.1.1.1.2.2.1). The major part of its application is as a chiral auxiliary, by the formation of esters or ethers. Esters with carboxylic acids may be formed by any convenient esterification technique. Esters with saturated carboxylic acids have been used for the formation of enolates by deprotonation and subsequent addition or alkylation reactions (Sections D.l.1.1.3.1. and D.l.5.2.3.), and with unsaturated acids as chiral dienes or dienophiles in Diels-Alder reactions (Section D. 1.6.1.1.1.), as chiral dipolarophiles in 1,3-dipolar cycloadditions (Section D.l.6.1.2.1.), as chiral partners in /(-lactam formation by [2 + 2] cycloaddition with chlorosulfonyl isocyanate (SectionD.l.6.1.3.), as sources for chiral alkenes in cyclopropanations (Section D.l.6.1.5.). and in the synthesis of chiral allenes (Section B.I.). Several esters have also been prepared by indirect techniques, e.g.,... 

A ten-membered ring derivative was prepared by the reaction of allene 7.91 with N-chlorosulfonyl isocyanate to give -lactam 7.92.51 Removal of the sulfonyl group and acid hydrolysis gave 10-amino-l-cyclodecene-l-carboxylic acid, 7.93. Similar... 

Aromatic isocyanates react with regular olefins only in the presence of metal catalysts. For example, reaction of ethylene with phenyl isocyanate in the presence of liganded nickel (o) catalysts under argon in THF at -20 °C affords a five-membered ring metalla-cycle, which on hydrolysis gives a Af-substituted carboxylic acid amide. Heating of the metallacycle causes jS-elimination with formation of Af-substituted acrylic acid amides Diolefines and allenes also undergo this reaction with phenyl isocyanate. From 1,1-bis-p-dimethylaminophenylethylene and p-nitrophenyl isocyanate a linear 1 1 adduct is obtained... 

Heating of the cycloadduct (R = CeHn) in pyridine causes formation of an isomeric cyloadduct resulting from addition across the C=N bond. A small amount of this isomer is also formed in the reaction with of the titana allene with t-butyl isocyanate. 

In the reaction of allenes with C=N heterocumulenes, such as isocyanates, isothiocyanates and carbodiimides, [2+2] cycloadducts or switter ionic linear 1 1 adducts are also formed. For example, from tetramethoxyallene and phenyl isocyanate the [2+2] cycloadduct is obtained Also, from tetrathiethylallene and p-toluenesulfonyl isothiocyanate the four-membered ring cycloadduct is formed In contrast, the same allene reacts with p-toluenesulfonyl isocyanate to give a [2+2] cycloadduct, which is in equilibrium with the linear switter ionic adduct. Using chlorosulfonyl isocyanate as the reagent, only a switter ionic product is formed Some [2+2] cycloadducts derived from allenes and isocyanates are listed in Chapter 3, Section 3.3.1. 

In the reaction of allene with phenyl isocyanate in the presence of a nickel (o) compound, the flve-membered ring metallacycle 259 is obtained, which on treatment with FeCls affords the diamide 260, formed by an oxidative coupling reaction... 

An ab initio study of the 2 + 2-cycloadditions of allene to isocyanic acid and ketene to vinylimine found the reactions to be concerted and mostly asynchronous.28,29 The diastereoselective 2 + 2-cycloaddition of dichloroketene with a chiral enol ether (26) produced the cyclobutanone (27), which leads to a key intermediate (28) in (g) the total synthesis of the natural alkaloid (-)-Swainsonine (29) (Scheme 8).30 The... 

Review. New synthetic reactions based on the onium salts of aza-arenes have been reviewed (75 references). The reactions discussed involve activation of carboxylic acids or alcohols with 2-haIopyridinium, benzoxazolium, benzothiazolium, and pyridinium salts to afford 2-acyloxy or 2-alkoxy intermediates, which can be transformed into esters, amides, thiol esters, (macrocyclic) lactones, acid fluorides, olefins, allenes, carbodiimides, isocyanates, isothiocyanates, and nitriles under appropriate conditions. 

The methods for generating acyl ketenes (Scheme 7-V) and their subsequent in situ participation in [4 + 2] cycloadditions with a wide range of hetero- or olefinic and acetylenic dienophiles (Scheme 7-VI), including acyl ketenes,185 186,197 carbonyl compounds, 86-188 nitriles,1874,189,191 isocyanates and isothiocyanates,1864,190,191 ketenes,191 imines,1864,1874,191,192 carbo-diimides,l87c 190,191,193 ynamines,194 ketene acetals,1864,195 enol ethers,1864,191,196 and V-sulfinylamines197 have been extensively reviewed.5,9,12 Two reports have detailed the 4-n- participation of allenic ketones in [4 + 2] cycloaddition reactions [Eq. (51)].198,199... 

Aromatic and aliphatic acyl isocyanates participate in a similar range of [4 + 2] cycloadditions although [2 + 2] and simple addition reactions often are observed. The acyl isocyanate substituents may determine or alter the observed course of the reaction, and the substituent effects have been detailed in extensive reviews.7,71 Observed [4 + 2] cycloadditions of acyl isocyanates with selected olefins, p-quinones, allenes, the carbon-carbon double bond of ketenes, electron-rich acetylenes, imines, dianils, ethy-lenediimines, enamines, enol ethers, ketene acetals, carbodiimides, azirines, and vinyl sulfides have been described.7 0 The reaction of aromatic acyl isocyanates with carbodiimides is not a simple, direct [4 + 2] cycloaddition but proceeds by a kinetic [2 + 2] cycloaddition followed by a subsequent rearrangement to provide the observed [4 + 2] cycloadduct [Eq. (40)].97... 

Electrophilic attack also occurs at the -Y-position of propargyl ligands, and this reaction converts propargyl complexes to allene complexes. An example of this protonation process is shown in Equation 12.61. This reaction has been used to initiate cycloaddition reactions. An example of this type of cycloaddition is the [3-t2] reaction of p-toluenesulfonyl isocyanate with the propargyl complex in Equation 12.62. Propargyl and Ti -allyl ligands are about equally reactive toward such cycloadditions. 

An isodesmic reaction has been employed to study substituent effects on the stability of ketenimines, XCH=C=NH. A (negative) correlation with the electronegativity of the substituent X was found. The sensitivity to the substituent effect is less than that for ketenes or isocyanates, but more than that found for diazomethanes or allenes. Particular stabilizing effects are found for tt-acceptors, e.g. X = AIH2, BH2, 0=CH, HO2C, CN, NO2, and HSO2 (suggesting cyano-cation resonance stmctures are important), and for X = Li (i.e. ynamine resonance). 

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