Chlorosulfonyl isocyanate, cycloaddition alkenes

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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). 

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. 

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]. 

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.,... 

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 ... 

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. 

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 in (2), this cycloaddition (in which preferentially the chlorosulfonyl isocyanate (8) is used) occurs stereoselectively, since the stereochemistry of the alkene is transferred... 

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. 

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