Allyl sulfonamides, synthesis

Sultams can also be accessed by intramolecular cyclization of compounds containing preformed C-S-N-C-C fragments with a C-C bond formation as demonstrated in a one-pot synthesis of tricyclic sultam 236 <05SL577>. Tetrahydropyridine 235, obtained from 77,7/-bis(allyl)sulfonamide 234 by ring-closure-metathesis (RCM) followed by isomerization, undergoes radical cyclization in the presence of tris(trimethylsilyl)silane (TTMSS) to give tricycle sultam 236. 

Several other types of domino reactions have been employed in the synthesis of natural products. Diastereoselective conversion of allylic carbonate 173 into enone 174 was one key transformation in a total synthesis of (+)-3-isorauniticine 175 (Scheme 27).Treatment of allylic sulfonamide 173 with a palladium catalyst re-gioselectively forms a 7r-allylpalladium intermediate by carbonate displacement. Carbopalladation of the pendant alkene, carbonylation, a second intramolecular alkene insertion, and /3-hydride elimination delivers a 67 22 11 mixture of stereoisomers of which enone 174 is the major product (isolated in 45-53% yield). Carbopalladation products can also undergo anion capture reactions. For instance, during the synthesis... 

Further examples of allyl substrates that proceed via a symmetrical intermediate include the allyl carbonate 161, which reacts with allyl sulfonamide 163 to give the product 164. Elaboration of compound 164 afforded the natural product mesembrane 165. Related strategies have been used in the synthesis of a range of other natural products. ... 

The synthesis of allyl sulfonamides by imidation of allyl sulfides with chloramine-T (TsNClNa) and subsequent [2,3]-sigmatropic rearrangement has been reported (Scheme 43). ... 

Tanaka and Ohno developed the palladium(0)-catalyzed cyclization of bromoallene 222 bearing a sulfonamide for the synthesis of medium-sized heterocycle 223 (Scheme 37).48b In this reaction, bromoallene acts as an allyl dication equivalent 224, and two different nucleophiles can be introduced regioselectively. The intramolecular nucleophilic... 

Tab. 10.6 summarizes the application of this transformation to a variety of racemic secondary allylic carbonates using the lithium anion of 4-methoxy-N-(p-toluidine)-benzene sulfonamide. The excellent regioselectivity obtained for this type of substitution provided an important advance in the synthesis of N-(arylsulfonyl)anihnes using the metal-catalyzed allyhc amination reaction. The allyhc alcohol derivatives examined... 

The Corey allylation system based on a chiral bis(sulfonamide) auxiliary was put to use with success in a number of synthetic efforts, including the total synthesis of the anticancer agent leucascandrolide (Scheme 13). Chiral reagent 152 is added to an achiral aldehyde, 3-(/ -methoxybenzyloxy)propanal, affording intermediate 153 in high stereoselectivity. The latter is transformed into a pyranyl aldehyde, which is subjected to a second allylation (this time, a doubly diastereoselective addition) en route to the completion of leucascandrolide. 

For the synthesis of protected allylic amines, a variety of synthetically useful carbamates and sulfonamides can be used, added to conjugated dienes [65]. Scheme 8.7 shows the proposed mechanism for these reactions. 

Snieckus reported a combination directed ortho-metalation (DoM)-RCM strategy for the synthesis of benzazepine, benzazocine, and benzannulated sulfonamide heterocycles <00SL1294> (Scheme 60). For example, the Boc-protected aniline (75) was sequentially allylated to give 76 which underwent RCM in excellent yield to give benzazepine 77. Use of similar methodology led to 78 and 79 starting from Y-methylbenzamide and p-tolylsulfonamide, respectively. 

The intermolecular addition of carbamates to 1,3-dienes (equation 147) under mild conditions has been described as well. The hydrothiolation of 1,3-dienes has also been reported. " Other related conjugate additions can be performed over methylenecyclopropanes (equation 148) with sulfonamides and the resulting product cyclizes by a second hydroamination of an olefin, finally yielding cyclic sulfonamides. This behavior is reproduced in a similar reaction for the ring opening of vinylcyclopropanes with sulfonamides. One more example in this group of reactions is the synthesis of dUiydrobenzofurans from aryl-allyl ethers. ... 

Treatment of lV-methanesulfonyl-l,4-dihydFopyridine with n-butyllithium, followed by benzyl bromide, leads to the corresponding lV-l-(2-phenylethyl)sulfonyl-l,4-dihydropyridine in low yield. The sulfonamide shown in Scheme 131 (entry c) has proved a valuable c -isoprenoid synthon which allows the two-step C -homologation of allyl halides. This synthon was used for the remarkable two-step stereoselective synthesis of nerol from 3-methyl-2-butenyl chloride (Scheme 131, entry c). Finally, the a-chloro dicarbanion of 4-(a-chlon>methanesulfonyl)morpholine is readily availabl on reaction with 2 equiv. of n-butyllithium in THF, and it leads to the corresponding dimethyl derivative with no detectable monoalkylated product or starting sulfonamide on methylation. Intramolecular versions of these reactions allow the low yield synthesis of neopentyl cyclopropanesulfonate (scheme 131, entry d) and the efficient preparation of cyclopropanesulfomorpholine (scheme 131, entry e). ... 

Such a procedure has been exploited for the synthesis of several derivatives for which an anti-inflammatory activity has been claimed [58]. A derivative under study as the Histamine H3 antagonist was prepared by the thermal intramolecular Diels-Alder reaction of a triene derivative of buta-1,3-diene-1-sulfonic acid amide. 1,3-Butadiene sulfonamides 182 (a 67%, b 69%, c 99%, d 51%) were prepared by the base mediated condensation of M-Boc-methanesulfonamides (181) with a series of aldheydes. N-akylation of 182 to give trienes 183 (a 69%, b 76%, c 82%, d 59%) was achieved by reacting the sodium salts with allyl bromide in THF at reflux. The intramolecular Diels-Alder reactions of compounds 183 were performed at 145 °C in toluene in a sealed vessel under argon. Under these conditions compounds 184 and 184 were obtained in good yields (a 76% ratio 6 1, b 71% ratio 6 1, c 92% ratio 3 1, d 87% ratio 3 1). 

Assorted anions. These are generated by deprotonation of allylic halides," chloromethylphosphonic esters, conjugated hydrazones, chiral carbamates,unsaturated a-aminonitriles, phosphonamides," and sulfonamides. The dianions derived from tu-haloalkanecarboxylic acids cyclize, and this reaction forms the basis of a synthesis of V-Boc cyclic imino acids. The conjugate bases of 2-(arylmethoxy)-methyl-2-oxazolines are unstable as [2,3]sigmatropic rearrangement takes place even at — 75°C. 

A synthesis of Agelastatin A by Weinreb and co-workers featured the use of a 13 bis[2-(trimethylsilyl)ethylsuifonyl] sulfodiimide 137 2 as an enophile in a two-step allylic amination reaction [ heme 8.137]. The initial ene reaction produced a dipolar intermediate 1373 that underwent a [2,3] Sigmatropic shift to afford the SES-protected allylic amine derivative 137,4. Reductive cleavage of the N-S bond followed by cleavage of the Boc group with trifluoroacetic acid gave the sulfonamide 1373 in 50-60% overall yield. Final deprotection of the SES group with TBAF returned the desired amine 137,6 in 90% yield. 

Polymer bound acrylic ester is reacted in a Baylis-Hillman reaction with aldehydes to form 3-hydroxy-2-methylidenepropionic acids or with aldehydes and sulfonamides in a three-component reaction to form 2-methylidene-3-[(arylsulfonyl)amino]propionic acids. In order to show the possibility of Michael additions, the synthesis of pyrazolones was chosen. The Michael addition was carried out with ethyl acetoacetate and BEMP as base to form the resin bound p-keto ester. This was then transformed into the hydrazone with phenylhydrazine hydrochloride in the presence of TMOF and DIPEA [28]. The polymer bound phenol was readily coupled to a variety of allyl halides by using the Pl- Bu to generate a reactive phenoxide [29]. 

Asymmetric Allylation Reactions. Enantioselective allylic alkylation is used extensively in asymmetric synthesis with chiral nonracemic phosphines often serving as the source of enantio-discrimination. A monodentate phosphabicyclononane derivative in conjunction with Pd(dba)2 was found to be effective in promoting the asymmetric allylation of 2-substituted cyclopen-tenyl and cyclohexenyl carbonates with malonate and sulfonamide nucleophiles with ee s ranging from 50 to 95% (eq 16). ... 

This allylation protocol was used in the total synthesis of amphidinolide to give homoallylic alcohol 12 in 72% yield and 17 1 dr (eq 5). Initial transmetallation of stannane 10 with (R,R)-1 via allylic transposition yielded an intermediate borane. Introduction of aldehyde 11 at -78 °C provided for a facile condensation reaction leading to 12. Stereocontrol was induced from the 1,2-diphenylethane sulfonamide auxiliary and could be predicted from a Zimmerman-Traxler model with minimized steric repulsions. The high level of selectivity obtained in this case was a result of a matched diastereomeric transition state featuring the inherent Felkin-Ahn selectivity for nucleophilic attack in aldehyde 11, with the (5)-configuration of the benzoate of 10, as well as the (7 ,7 -antipode of auxiliary 1, resulting in threefold stereodifferentiation. 

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