Sultams chlorides

The same stereochemical result is obtained when the horyl cnolate 4, derived from sultam 1 is transmetalated by the addition of titanium(lV) chloride and subsequently reacted with aldehydes106g. 

Hanessian reported the synthesis of enantiomerically pure or highly enriched allylglycine and its chain-substituted analogs from the reaction of the sultam derivatives of O-benzyl glyoxylic acid oxime with ally he bromides in the presence of zinc powder in aqueous ammonium chloride (Eq. 11.41).72 Brown noticed the critical importance of water in the asymmetric allylboration of /V-trimethylsilyIbcnzaldimines with B-allyldiisopinocampheylborane.73 The reaction required one equivalent of water to proceed (Eq. 11.42). 

The sultam, sulthiame (170), shows anticonvulsant activity. p-Aminobenzenesulfonamide can be alkylated by w-chlorobutylsulfonyl chloride (168) in... 

Sultam 53 has proved to be an excellent chiral auxiliary in various asymmetric C-C bond formation reactions. One more example of using sultam 53 is the asymmetric induction of copper(I) chloride-catalyzed 1,4-addition of alkyl magnesium chlorides to a,/ -disubstituted (/ )-enesultams 60. Subsequent protonation of the reaction product gives compound 61c as the major product (Scheme 2-30 and Table 2-11).56... 

Dipolar addition is closely related to the Diels-Alder reaction, but allows the formation of five-membered adducts, including cyclopentane derivatives. Like Diels-Alder reactions, 1,3-dipolar cycloaddition involves [4+2] concerted reaction of a 1,3-dipolar species (the An component and a dipolar In component). Very often, condensation of chiral acrylates with nitrile oxides or nitrones gives only modest diastereoselectivity.82 1,3-Dipolar cycloaddition between nitrones and alkenes is most useful and convenient for the preparation of iso-xazolidine derivatives, which can then be readily converted to 1,3-amino alcohol equivalents under mild conditions.83 The low selectivity of the 1,3-dipolar reaction can be overcome to some extent by introducing a chiral auxiliary to the substrate. As shown in Scheme 5-51, the reaction of 169 with acryloyl chloride connects the chiral sultam to the acrylic acid substrate, and subsequent cycloaddition yields product 170 with a diastereoselectivity of 90 10.84... 

A somewhat similar isomerization was observed with the sultam 5-methylimino-4-phenyl-l,3,4-dithiazolidine 1-dioxide (17 i = H). On heating at 60°C in the presence of benzoyl chloride, rearrangement into the isomeric 5-phenylimino-4-methyl-l,3,4-dithiazolidine 1-dioxide (19, 1 = H) was found (Scheme IV.ll). As intermediate can be proposed the amidinium salt 18 (78JOC4951). Furthermore, NMR-controlled test tube experiments revealed that this rearrangement also occurs under influence of aluminum trichloride and methanesulfonyl chloride. Also, the 2-phenyl derivative 17 (R = CeHs) could be isomerized it required heating in acetone with m-dichlorobenzoic acid as catalyst (Scheme IV.ll). 

A five-membered sultam was prepared from A,A -dibenzoylcystine diethyl ester via a sulfonyl chloride and sulfonamide (Scheme 30) (60CB784). 

As mentioned in the introduction, recent synthetic developments now allow access to the 1,2-thiazine structure via disconnection type C (Figure 23). This process can be accomplished by a Friedel-Crafts-type cyclization of sulfamoyl chlorides. The initial report of this reaction utilized a stoichometric amount of aluminium chloride promoter <19920PP463>. Recently, however, A -ethyl phenethylsulfamoyl chloride 214 was shown to undergo Friedel-Crafts cyclization to form sultam 215 with just a catalytic amount of In(OTf)3 (Equation 33) <2002SL1928>. 

Oppolzer et al. (321) applied his own sultam as the auxiliary for a cychc nitrone in the synthesis of (—)-allosedamine (Scheme 12.60). The enantiomerically pure nitrone 209 was synthesized from 208 by base treatment, attack of the enolate on 1-chloro-l-nitrosocyclohexane at the nitrogen atom, and subsequent elimination of chloride. Subsequent addition of aqueous HCl gave the cyclic nitrone 209. The nitrone participated in a 1,3-dipolar cycloaddition with styrene, proceeding with complete exo-specificity. The product, 210, was obtained with a de of 93%. Two further reaction steps yield the piperidine alkaloid ( )-aUosedamine 211 in an overall yield of 21%. 

Jurczak and Kiegiel reported that additions of allylmagnesium chloride and allyl bromide in the presence of Zn to iV-methyl and W-phenylglyoxyloyl-(2R)-borane-10,2-sultam occurred in a diastereoselective manner. Similarly, the Lewis acid mediated addition of allyltrimethylsilane also gave good diastereoselectivity and in the case with TiCU a change of direction of asymmetric induction was observed <99TL1009>. 

Formally, the synthetic route outlined in Scheme 6 constitutes the preparation of a new ring system from another. Nucleophilic attack of amine on the sulfonate ester, a particularly good leaving group, leads to monocyclic compound 67. Conversion of the sulfonic acid moiety into a sulfonyl chloride by POCI3 then yields the sulfonyl chloride siVu, which then undergoes nucleophilic attack by the pendant amine resulting in the chiral sultam 68. 

V-Acylbornane-l 0,2-sultams 2 are prepared from the bornane-10,2-sultam 1 via NH-deproto-nation with sodium hydride and subsequent acylation with a suitable acid chloride. 

With an excess of the lithiating agent, 1-benzenesulfonylindoles form dilithiated derivatives, which may be dialkylated or dideuterated (81JHC807). Reaction with carbonyl compounds, however, may result in the formation of the 2-substituted indole with cleavage of the protecting group (Scheme 37), although the reaction with benzoyl chloride yields the sultam (134). 

Sulfonyl chlorides possessing an a-hydrogen undergo elimination of hydrogen chloride when treated with bases to yield sulfenes. Like ketenes, sulfenes can undergo [2 + 2] cycloaddition to support-bound imines to yield p-sultams (Entry 5, Table 15.2). 

Selective C-S bond cleavage of a /3-sultam ring bearing a variety of substituents at C-3 and C-4 can be achieved by reaction with Lewis acids and yields aryl ketones or aldehydes. A solution of ethylaluminium dichloride in hexane is easier to handle than solid aluminium chloride due to their relative moisture sensitivities (Scheme 25) <1998T8941>. 

Substitution of the acetate group at the C-3 position of the /3-sultam 105 can occur by reaction with silyl enol ethers in the presence of zinc iodide or zinc chloride. When the diazo compound is used, after desilylation with tetrabutyl-ammonium fluoride (TBAF), photochemical cyclization gives the bicyclic /3-sultam 106 as a mixture of two cis/ fra -diastereoisomers. When silyl enol ethers derived from cyclic ketones are used, the substitution product is stabilized by a retro-Michael-type reaction leading to open-chained sulfonamides 107 (Scheme 31) <1997LA1261>. 

A synthetic approach to /3-sultams containing a direct bond between a tri- or tetracoordinated phosphorus atom and the nitrogen atom of the 1,2-thiazetidine 1,1-dioxide ring has been realized by direct phosphitylation or phosphorylation at nitrogen. Unfortunately, attempts to synthesize N-phosphorylated /3-sultams by reaction with diethyl phosphorochloridate and diethyl phosphorobromidate, generated in situ from diethyl phosphate and carbon tetrachloride or carbon tetrabromide, failed. However, when the /3-sultam is treated with freshly distilled diethyl phosphorochloridite or tetramethylphosphorodiamidous chloride in the presence of triethylamine, the expected AHliethy I phosphite and iV-phosphorodiamidous /3-sultams 150 are obtained (Equation 10). /3-Sultams unsubstituted... 

Monosilyl 3-sultams are prepared using [2+2] cycloaddition by treatment of methanesulfonyl chloride and an aryl or tert-butylimine in THF at room temperature. Better yields are obtained using a /-butylimine (83%) than an aryl imine (18-59%) (Equation 14). /3-Sultams obtained as a mixture of two isomers are separable by silica gel column chromatography <1998CPB757>. 

The synthesis of 3-alkyl-substituted 1,2-thiazetidine 1,1-dioxides starts by transformation of the amino acids L-Val, L-Leu, L-Ile, and L-Phe into amino alcohols. These ate converted via the bromides to the corresponding thiols 161. Immediate oxidative chlorination affords either sulfonyl chloride hydrochlorides or sulfonic acids 162 which are transformed into the parent /3-sultams 163 <2004HCA90>. Similarly, L-cystine derivatives 164 have also been transformed into the parent /3-sultams 165 by oxidative chlorination followed by cyclization (Scheme 50) C1997LA1261, 2004HCA90>. 

Triphenylphosphine dichloride was used as a mild halogenating reagent to transform the sodium sulfonate salt 175 into the corresponding sulfonyl chloride. Further treatment using triethylamine gave the / -sultam 77 in satisfactory yield (Equation 15) <1998S423>. 

An efficient asymmetric synthesis of the 3-substituted /3-sultams 163 has been reported. The key step of the synthesis is the Lewis acid-catalyzed aza-Michael addition of the enantiopure hydrazines (A)-l-amino-2-methoxy-methylpyrrolidine (SAMP) or CR,l ,l )-2-amino-3-methoxymethyl-2-azabicyclo[3.3.0]octane (RAMBO) to the alke-nylsulfonyl sulfonates 176. /3-Hydrazino sulfonates were obtained in good yield and excellent enantioselectivity. Cleavage of the sulfonates followed by chlorination resulted in the corresponding sulfonyl chlorides 177. The (A)-3-substituted /3-sultams 163 have been obtained in moderate to good yields and high enantioselectivity over two steps, an acidic N-deprotection followed by in situ cyclization promoted by triethylamine (Scheme 55) <2002TL5109, 2003S1856>. 

The successful application of sulfanyl amines in the diastereoselective and enantioselective synthesis of as-3,4-disubstituted /3-sultams has been reported (Scheme 56). The protocol is based on the oxidation of the 1,2-aminothiols 178 with hydrogen peroxide and ammonium heptamolybdate. Chlorination of the resulting /3-aminosulfonic acids was achieved using phosgene. The /3-aminosulfonyl chlorides 179 obtained were cyclized under basic conditions and without epimerization to yield the t -3,4-disubstituted /3-sultams 180 (>96% de, ee) (Table 13) <2005S1807>. 

Table 13 Synthesis of the c/s-3,4-disubstituted, 3-sultams 180 by cyclization of the 1,2-aminosulfonyl chlorides 179 <2005S1807>...

Sultams are accessible using a [2+2] cycloaddition reaction between an alkylsulfonyl chloride and an aryl or /-butylimine, better yields being obtained in the latter case. A diastereoselective synthesis of these /3-sultams has been described where 1,3-asymmetric induction occurs in a [2+2] cycloaddition between a sulfene intermediate and... 

Enantioselective fluorination. The N-fluoro sultams 1 and 2 are prepared from the imine available from ( + )-camphor-10-sulfonyl chloride. 

Sulfenes, generated in situ from alkylsulfonyl chlorides and triethylamine, react with thiatriazoline (50) to give sultams (53). The sultams isomerize on heating at 60 °C in the presence of benzoyl chloride, or A1C13 and methanesulfonyl chloride (equation 24). 

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