Chlorosulfonyl isocyanate 2+2 cycloadditions

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 e, 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... 

Substituted azocine systems are much more stable than the parent compound, and 2-methoxy derivatives have been intensively examined. Starting from cyclohexa-1,4-diene (3), a [2 + 2] cycloaddition with chlorosulfonyl isocyanate, followed by removal of the chlorosulfonyl group, leads to the /3-lactam 4, which can be transformed by O-methylation with Meerwein s salt into the corresponding imidate. Monobromination with A-bromosuccinimide and subsequent treatment with base results in a methoxyazabicyclo[4.2.0]octatriene derivative, which spontaneously isomerizes to 2-methoxyazocine (5).13,14... 

The nitrogen atoms in ADC compounds are highly electrophilic. Nucleophilic attack on nitrogen is easy, and as with electrophilic acetylenes, such as dimethyl acetylenedicarboxylate, it seems likely that some cycloaddition reactions of ADC compounds with unsymmetrical substrates proceed via a stepwise mechanism. PTAD is a powerful electrophile, although TCNE is more reactive, and chlorosulfonyl isocyanate is more reactive still.58... 

I.3.4.2.4. Heterocumulenes The 1,3-dipolar cycloaddition of substituted ben-zonitrile oxides to the C=N group of chlorocarbonyl isocyanate C1C(0)N=C=0 gives 3-aryl-4-chlorocarbonyl-5-oxo-4,5-dihydro-l,2,4-oxadiazoles 172 in 75%-80% yield (340). A similar reaction with chlorosulfonyl isocyanate, C1S02N=C=0, affords 4-unsubstituted oxadiazolinones 173 (341). 

An approach to biotin [166] starts from a [2 + 2] cycloaddition of chlorosulfonyl isocyanate to chromene. The excellent regioselectivity of this reaction may be attributed, at least in part, to the ethereal oxygen. 

Moricini and Kelly [75] have reported the synthesis of spiro-fi-lactams 6 containing an exocyclic double bond (Scheme 2) by the 1,2-dipolar cycloaddition of symmetrically/unsymmetrically substituted allene 4 with chlorosulfonyl isocyanate 5 in ether. 

Georgiev et al. [82] have described the preparation of novel adamantine-spiro-heterocyclic (3-lactams 34, 35, and 40. Grignard reaction of 2-adamantanone 31 with benzylmagnesium halide provided the compound 32, which on further dehydration afforded corresponding analogs 33. Condensation reaction of compound 33 with chlorosulfonyl isocyanate in ether afforded spiro-(3-lactams 34 and cycloaddition with chlorosulfonyl isocyanate resulted in the formation of spiro product 35 (Scheme 10). 

Starting from the commercially available (+)-3-carene, the cycloaddition of chlorosulfonyl isocyanate [228] has been reported to furnish the enantiomeric (3-lactam in a regio- and stereoselective manner [229]. Treatment of the (3-lactam with di-ferf-butyl dicarbonate resulted in iV-Boc (3-lactam, that could be readily opened under mild conditions (Scheme 104). 

The 2 + 2-cycloaddition of chlorosulfonyl isocyanate with chiral alkoxyallenes, derived from ethylidene and benzylidene L-erythritol and D-threitol, produces azetidi-nones that are readily converted into the corresponding tricyclic cephams. NMR and CD spectroscopy were used to assign the absolute configurations of the azetidinones... 

The classical reaction with chlorosulfonyl isocyanate has been extended to it-vinyl sulfide 449 to give a 2.5 1 diastereomeric mixture of 4-(phenylthio)azetidin-2-ones 343 and 450 (Equation 180) <2000MI935>. The facial selectivity in the cycloaddition has been explained by the conformational preference of the allylic groups in the transition structure. A similar reaction with styrene resulted into synthesis of the racemic 4-aryl-azetidin-2-one (Equation 181) <2000TA2351>. The divinyl ether 451 reacted with acid-free chlorosulfonylisocyanate to form 4-vinyloxyazetidin-2-one 452 (Equation 182) <1996SL895, 1997TA2553, 1998TL8349>. Most of the results in the reactions of isocyanate with vinyl ethers could be rationalized by a -conformational preference of the ether in... 

Spontaneous reaction of iV-chlorosulfonyl isocyanate with a-substituted allylsilanes is valuable for the synthesis of 4-silyl-2-pyrrolidinones.179-181 The [3 + 2]-cycloaddition of crotylsilanes proceeds stereospecifically as does the... 

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. 

Graf [103] originally proposed a two-step mechanism for the cycloaddition of chlorosulfonyl isocyanate to alkenes. This leads to the 1,4-dipole shown in Eq. (5-35), which can then ring close to give a y9-lactam (and as by-product an unsaturated amide via a proton shift from R or R to N ). Moriconi [104], on the other hand, has proposed a nearly concerted, thermally allowed +, j2a] cycloaddition, probably initiated by a r-complex formation, and proceeding through the dipolar activated complex shown in the lower part of Eq. (5-35). 

W-C4H9) [106, 107]. Ab initio MO calculations have shown that the [2 - - 2] cycloaddition between cis- or Jraw-alkenes and isocyanates to yield y9-lactams takes place by a concerted mechanism in the gas phase, with retention of the alkene configuration in the product. However, increasing solvent polarity contributes to the asynchronicity of the reaction to such an extent that the mechanism changes from a concerted to a two-step process involving a zwitterionic intermediate, with a consequent loss of alkene stereospecificity, as observed in the reaction between chlorosulfonyl isocyanates and vinyl ethers [794]. 

FIGURE 10.1 Diasterofacial differentiation in [2+2]-cycloaddition of chlorosulfonyl isocyanate with carbohydrate vinyl ethers 47. 

Kaluza, Z, Furman, B, Patel, M, Chmielewski, M, As3fmmetric induction in [2 + 2] cycloaddition of chlorosulfonyl isocyanate to l,2-0-isopropylidene-3-0-vinyl-glycofuranoses. Tetrahedron Asymmetry, 5, 2179-2186, 1994. 

CYCLOADDITIONS f-Butyicyanoketene. a-Chloro-N-cyclohexylpropanaldoxime. Chlorosulfonyl isocyanate. Dichloroke-tene. Dimethyl acetylenedicarboxylate. Diphenyl ketene, 2-Methoxyallyl bromide. 2-Methoxy-6-methyl-l,4,3,5-oxathiadia-zine 4,4-dioxide. Oxygen, singlet. 4-Phen-yl-l,2,4-triazoline-3,5-dione. Silver fluoro-borate. Trimethylsilyldiazomethane. 

Two groups have independently explored dipolar cycloadditions of oxiranes with chlorosulfonyl isocyanate. Treatment of oxiranes with C1S02N=C=0 in benzene <84JHC1721, 84SC687) or in CH2C12 <86SC123> gives rise to either cyclic carbonates or 2-oxazolidones, or both after hydrolytic workup (Equation (27)). 

When bicyclopropylidene reacted with chlorosulfonyl isocyanate the ) -lactam 17 resulting from [2 + 2] cycloaddition was a minor product. The main product was 5-chlorosulfonyl-7-methylene-5-azaspiro[2.4]heptan-4-one (16). ... 

A C-C double bond was also formed on reaction of dicydopropylacetylene with chlorosulfonyl isocyanate. Conceivably a [2-1-2] cycloaddition took place to give an unstable product that rearranged to 6-chloro-4,5-dicyclopropyl-l,2,3-oxathiazine 2,2-dioxide in 96 /o yield. ... 

Dipolar intermediates are very likely in all [6 + 2] cycloadditions with chlorosulfonyl isocyanate. 

Bishomotropylium ions are postulated as intermediates in the cycloadditions of TCNE and chlorosulfonyl isocyanate onto c -bicyclo[6.1.0]nonatrienes... 

The cycloaddition of alkenylidenecyclopropanes 5 with chlorosulfonyl isocyanate is described via electrophilic attack at C4, disrotatory opening of the cyclopropane ring to form a dipolar intermediate 8, and ring closure by nucleophilic attack of nitrogen or oxygen on either end of the allyl cation portion of the intermediate 8 which gives adducts 9-12. [27t -I- 2tc] Products 13 were also obtained. 

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