Chlorosulfonyl isocyanate 6+2 cycloaddition reactions

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. 

RHF methodology, used to investigate the cycloaddition reaction of isocyanic acid with methylenimine, confirmed a two-step mechanism via a cis intermediate for the equimolar reaction.22 The 2 + 2-cycloaddition of chlorosulfonyl and trichloroacetyl... 

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). 

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 study of [2 + 2]cycloaddition of chlorosulfonyl isocyanate (CSI) to a variety of l,2-0-isopropylidene-3-0-vinyl-D-glycofuranoses (Scheme 32) showed that the observed high selectivity of these reactions was steri-cally controlled and depended on the size of the substituent at C-5 of the sugar [89]. The /3-lactams 113 and 114, obtained from vinyl ethers 112, were transformed into the corresponding cephams 115-118 by the intramolecular alkylation of the j6-lactam nitrogen atom [89,90]. [2 -I- 2]Cycloaddition of CSI to (Z) and (E) vinyl ethers proceeds stereospecifically with asymmetric induction in the range reported for simple vinyl ethers to afford corresponding cis and trans /3-lactams [91,92]. 

A theoretical study of the catalytic and substituent effects on the 2 - - 2-cycloaddition reactions between isocyanates and aldehydes was presented. Steady-state NOE coefficients have been used to develop a stereochemical model for the transition state for 2 -I- 2-cycloaddition of chlorosulfonyl isocyanate with chiral vinyl ethers. The asymmetric 2 -I- 2-cycloadditions of chlorosulfonyl isocyanate to chiral vinyl ethers derived from sugars and hydroxy/acids have been reviewed. 

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... 

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). 

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... 

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]. 

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. ... 

An alternative approach to the p-lactam ring system uses the cycloaddition of an alkene with an isocyanate such as chlorosulfonyl isocyanate (0=C= N—SOiCl). For example, reaction of cyclopentadiene with chlorosulfonyl isocyanate gave the p-lactam 183 (3.121). The A-unsubstituted -lactam is formed under these conditions owing to the ease of removal of the SO2CI group. The regioselectivity can be explained by combination of the more electron-rich end of the alkene with the electron-dehcient carbon atom of the isocyanate. 

Owing to the importance of p-lactam antibiotics, the [2+2]cycloadditions of ketenes to imines and isocyanates to olefins play a special role because both reactions lead to direct formation of a four-membered azetidinone-2 ring. The first one can be performed using a large variety of ketenes and ketene equivalents, whereas the second one leads to useful compounds only in the case of chlorosulfonyl isocyanate and vinyl acetates, vinyl silyl ethers, and dienes. One example of the addition of an isocyanate to a vinyl ether has been reported (Scheme 1). ... 

The reaction between tri-O-acetyl-D-glucal 7 and chlorosulfonyl isocyanate has been studied in the past, but neither formation of a cycloadduct nor of a rearranged product has been observed. Isocyanate acted only as acid catalyst causing decomposition of sugar material. On the other hand, [2+2]cycloaddition of active isocyanates to dihydro-2H-pyran and to its derivatives has been widely investigated, under a variety of conditions. The reaction of tosyl isocyanate with dihydro-2H-pyran 1 at low temperature (0 ) led to the formation of bicyclic p-lactam 2. Elevation of the cyclization temperature resulted in the rearrangement of the four-membered ring to the open-chain amide 3 (Scheme 4). 

Silver acetate catalyses the cycloaddition of methyl isocyanoacetate with electron-deficient alkenes to produce A - or A -pyrrolines in good yields. The reaction of 3-acetoxy-l-methylallylsilane with A-chlorosulfonyl isocyanate at 0°C produces the... 

As a Carbon Nucleophile in Uncatalyzed Reactions. Some electrophiles do not need Lewis acids, being already cationic and electrophilic enough to react with allyltrimethylsilane. Examples are the dithianyl cation (eq 20), the tricarbonyl(cyclohexadienyl) iron cation (eq 21), ( r-allyl) tetracarbonyliron cations, and chlorosulfonyl isocyanate (CSI). Other reagents react directly by cycloaddition, but need further steps to achieve an overall electrophilic substitution, as in the reactions with nitrones (eq 22). 

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