Isocyanates, cycloaddition with alkenes

The high reactivity of CSI is probably associated with the powerful electronwithdrawing character of the chlorosulfonyl moiety, which activates the adjacent isocyanate group with respect to nucleophilic addition. The [2 + 2] cycloadditions with alkenes may therefore be depicted as in Scheme 33. 

Woodward s synthesis, 4, 416-419 Chlorophyll b, 4, 382 Chlorophyll c, 4, 382 Chlorophyll d, 4, 382 Chlorophylls, 4, 378 biosynthesis reviews, 1, 99 structure, 4, 370 substituents reactions, 4, 402 Chloroporphyrin e6, 4, 404 Chloroprothixene pharmacology, 3, 942 Chloropyramine as antihistamine, 1, 177 Chloropyrifos synthesis, 2, 201 Chloropyrifos-ethyl as insecticide, 2, 516 Chloropyrifos-methyl as insecticide, 2, 516 Chloroquine, 1, 145 adsorption on nucleic acids, 1, 179 as antimalarial, 1, 173, 2, 517 Chloroquine, hydroxy-as antimalarial, 2, 517 Chlorosulfonyl isocyanate cycloaddition reactions with alkenes, azetidin-2-ones from, 7, 261 reactions... 

One of the most facile methods for construction of the (i-lactam skeleton would be [2 + 2] cyclo additions of isocyanates to alkenes. However, the [2 + 2] cycloadditions of alkyl or aryl isocyanides with either 2,3-dihydrofuran or vinyl ethers often fails under normal conditions. High pressure can surmount this difficulty in certain cases. For instance, alkyl isocyanates 125 underwent [2 + 2] cycloadditions with such cyclic vinyl ethers as 126 to produce the P-lactams 127 (Scheme 34) [80]. 

Various unsaturated compounds, such as CO2, isocyanates and aldehydes, undergo Pd-catalysed cycloaddition with vinyl epoxides. Reaction of CO2 with 127 affords cyclic carbonates 128 with retention of the configuration at C(3), offering a method of cis hydroxylation of epoxides [66], and has been used for the synthesis of the side-chain unsaturated (—)-exo-brevicomin (129) [67], The tetrahydrofuran 131 was prepared by [3+2] cycloaddition of activated alkenes such as benzylidene malononitrile (130) with vinyl epoxide via Michael addition and allylation [68],... 

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. 

When we wish to make (3-lactams by the alternative addition of an isocyanate to an alkene, a substituent on nitrogen is again required, but for quite a different reason. Because alkenes are only moderately nucleophilic, we need a strongly electron-withdrawing group on the isocyanate that can be removed after the cycloaddition, and the most popular by far is the chlorosulfonyl group. The main reason for its popularity is the commercial availability of chlorosulfonyl isocyanate. It reacts even with simple alkenes. 

The thermal [2 + 2J cycloaddition of cumulenes with alkenes, imines, and carbonyl compounds is one of the most useful routes to four-membered ring compounds. Ketenes and keteniminium salts add to alkenes to give cyclobutanones (Houben-Weyl Vol. IV/4 pp 174 205) 41 al-lenes add to alkenes to give methylenecyclobutanes (Houben-Weyl Vol. IV/4 pp 151-173), ketenes add to carbonyl compounds to give //-lactones (Houben-Weyl Vol. VI/2 pp 520-527), ketenes add to imines to give /1-lactams, and isocyanates add to alkenes to give //-lactams (Houben-Weyl Vol. V/lb p 1098). 

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.,... 

The synthesis of a series of isoxazoles 15 and isoxazolines 15a on the solid phase has been reported by Pei and Moos [50] via [3 + 2] cycloaddition of alkenes and alkynes with highly reactive nitrile oxides. The cycloaddition reactions of resin-bound peptoids were carried out in toluene at 100°C or in DCM-H2O at room temperature, depending on the precursors of the nitrile oxides. Benzaldehyde oxime and various nitroalkyl compounds were selected as nitrile oxide precursors. The nitrile oxides were generated in situ by reacting the nitroalkyl compounds with phenyl isocyanate and triethylam-ine or by oxidizing the oximes with sodium hypochlorite in the presence of triethylamine (Fig. 7). 

Ketenes react with imines via [2+2]-cycloaddition to produce P-lactams.278 An example is the reaction of the acid chloride of phenylacetic acid with Proton Sponge to give ketene 340, which reacted with the tosyl imine shown and a quinuclidine catalyst to give a 65% yield of P-lactam 341, in 96% ee.229 A-Substituted isocyanates also undergo thermal [2+2]-cycloaddition reactions with alkenes, generating P-lactams.280... 

Chlorosulfonyl isocyanate is prepared from chlorocyanogen and sulfur trioxide. It reacts with alkenes to form 1-chlorosulfonyl azetidin-2-ones, from which the corresponding compounds, unsubstituted in the 1-position, can be obtained by the action of thiophenol. The cycloaddition occurs stereospecifically cw-azetidin-2-one is formed from a Z-alkene ... 

Jochims [134] and Hassan s [135] groups reported the efficient use of l-aza-2-azoniaallene salts 119 and 0-acetylated j6-D-glucopyranosyl isothiocyanate 89 for the preparation of glucopyranosylimino-l,3,4-thiadiazoles 121 and 122. These salts, prepared from chloroalkylazo derivatives 118 and antimony (V) chloride, can undergo 1,3-dipolar cycloadditions with multiple bonds-containing compounds, such as alkynes, alkenes, isocyanates, isothio-... 

Neooctams, such as the unsubstituted parent compound (191), are easily obtained in cycloadditions. Isocyanates [125,126], sulphonyl isocyanates (43) [29,127] and especially chlorosulphonyl isocyanate (189) [128] react with alkenes to form variously-substituted j3-lactams [129—135]. Synthesis of compound (191) is an example of this reaction which has been discussed in detail [52]. The same compound (192) can be obtained in the photolytic rearrangement of the pyrazolone (194) [136]. Compound (196) is neooctam-5,7-diene, obtained from the azocine (195) and hydrogen bromide [137]. Lactam (196)is a partly saturated form of (199). The latter is an unstable neooctam derivative, formed in an intramolecular ketene-imine cycloaddition reaction (see (198))... 

The cycloaddition of alkenes is quite general and has been extended to the formation of azanickelacycles 12 by using isocyanates instead of CO2 in the reaction with alkenes or 1,3-butadienes (Eq. 6). These... 

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