8-Lactams, from chlorosulfonyl isocyanate

Lactams, from chlorosulfonyl isocyanate, 46, 27 preparation of, 46,56 18,20-Lactone op 3 -acetoxy-208-hy-deoxy-S-pregnene-18-oic acid, 46,57... 

While the formation of cyclobutanones froradichloroketenes and P-lactams from chlorosulfonyl isocyanates generally showed very good regioselectivity [133], a high... 

Scheme 38 Formation of chiral [S-lactams (155) from chlorosulfonyl isocyanate (148) and homochiral enol ethers (154)...

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... 

On the pages which follow, general methods are illustrated for the synthesis of a wide variety of classes of organic compounds including acyl isocyanates (from amides and oxalyl chloride p. 16), epoxides (from reductive coupling of aromatic aldehydes by hexamethylphosphorous triamide p. 31), a-fluoro acids (from 1-alkenes p. 37), 0-lactams (from olefins and chlorosulfonyl isocyanate p. 51), 1 y3,5-triketones (from dianions of 1,3-diketones and esters p. 57), sulfinate esters (from disulfides, alcohols, and lead tetraacetate p. 62), carboxylic acids (from carbonylation of alcohols or olefins via carbonium-ion intermediates p. 72), sulfoxides (from sulfides and sodium periodate p. 78), carbazoles... 

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). 

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]. 

An alternative route to chiral p-lactams was provided by reactions of electron-deficient isocyanates with chiral nucleophilic alkenes such as vinyl ethers or vinyl acetates. Chlorosulfonyl isocyanate (CSI), a commonly used reactive isocyanate [34], undergoes stereospecific 5-yn-addition to alkenes. The chlorosulfonyl group can subsequently be reductively removed from the nitrogen atom. It has been shown that reactions between CSI and (Z)- and ( )-alkenyl ethers stereoselectively give cA-3,4-disubstituted azetidinones from (Z)-olefins and tmns-3,4-... 

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). ... 

Azetidin-2-ones are more reactive than y- and <5-lactams because of ring strain. This is true for the alkaline fission to give salts of / amino carboxylic acids, as well as for the acid-catalysed hydrolysis to fi-carboxyethylammonium salts. Starting from alkenes and chlorosulfonyl isocyanate, a stereocontrolled synthesis of / -amino carboxylic acids can be realized. Ammonia and amines react with azetidin-2-ones, also with ring-opening, to produce / -amino carboxylic amides. Hence they are acylated by azetidin-2-ones ... 

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]. 

Alkoxyallene 140 derived from 1,3-benzyHdene-L-erythritol treated with chlorosulfonyl isocyanate provided diastereomeric S-lactams 141 with a moderate stereoselectivity, these after the intramolecular alkylation of the nitrogen atom afforded compounds having oxacepham skeletons which were... 

The D-g/wco-pentitol-l-yl substituted uracil 96 and its D-galacto-isomer were synthesized from tri-O-benzyl-D-glucal and -o-galactal, respectively, by [2+2]cy-cloaddition of trichloroacetyl or chlorosulfonyl isocyanate, cleavage of the p-lactam rings in the products with methanol after AT-carbamoylation, and cycliza-tion of resulting glycosylureas. Tosylation of 4-(D-ga/acro-pentitol-l-yl)-2-phenyl-2/f-l,2,3-triazole led to the 3,6-anhydride 97 and two partially tosylated derivatives. ... 

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