Allenic sulfonamide

An a-allenic sulfonamide undergoes Pd-catalyzed carbonylative cyclization with iodobenzene, affording a mixture of isomeric heterocycles (Scheme 16.12) [17]. The coupling reaction of an allene with a PhCOPdl species takes place at the allenyl central catrbon to form a 2-acyl-Jt-allylpalladium complex, which is attacked by an internal sulfonamide group in an endo mode, affording a mixture of isomeric heterocycles (Scheme 16.13). 

The Ru-catalyzed cyclocarbonylation of a-allenic sulfonamides proceeds in the presence of Et3N under a CO atmosphere (20 atm) to yield ,/funsaturated lactams (Scheme 16.32) [36], In order to gain an insight into the reaction mechanism, a deuterium-substituted a-allenic sulfonamide was subjected to the carbonylation. The deuterium was found to be totally transferred to the methyl group. Based on this observation, a mechanism has been proposed which involves a ruthenacycle derived from addition of the Ru-H to the terminal double bond of allene (Scheme 16.33). 

Similarly, ruthenium(0)-catalyzed cyclocarbonylation of allenic sulfonamides 41 yielded y- and <5-unsaturated lactams 42 (Eq. 20) [30]. The lactam formation is claimed to start with the oxidative addition of a Ru(CO)4 fragment into the N-H bond of 41. Subsequent syn addition of the resultant Ru-H species to the... 

Like their unprotected counterparts, a-allenic sulfonamides of the type 404, which are easily accessible by lithiated methoxyallene to N-tosylimines, can be cyclized to the corresponding 3-pyrrolines (e.g., 405) in the presence of substoichiometric amounts of silver nitrate (Equation (21)).337,337a The method can be applied to the synthesis of mono- or bicyclic products which were obtained with moderate to good yields. The analogous cycloisomerization of /Uallenic sulfonamides to tetrahydropyridins was developed by Ibuka and co-workers.338... 

The cyclization of the allenic sulfonamide 8, performed by treatment with silver tetrafluoro-borate in dichloromethane, gave the //a .v-2,3-disubstituted pyrrolidine derivative 9 exclusively. The configuration was assigned by 111 NMR217. 

Kang, S.-K. and Kim, K.-J. (2001) Palladiiun (0)aryl iodides and carbon monoxide. Organic Letters, 3, 511-514. 

For the cyclization of the less nucleophilic sulfonamides, this conversion can only be achieved via this two-step protocol. The addition of I2 was highly regioselective, addressing the terminal C=C bond, whereas the second step could deliver several products including the SN2-substitution, SN2 -substitution and bimolecular double substitution products 297-299, depending on the length of the tether connecting the amine and the allene moiety [144, 145],... 

In situ epoxidation of allenyl alcohols [20], aldehydes [21], acids [22] and sulfonamides [23] followed by intramolecular ring opening of the intermediates was thoroughly investigated by Crandall and co-workers. They showed that products formed either from the allene oxide or the spirodioxide intermediate can be prepared selectively. Allenyl acids 56, for example, react first with DMDO on their more substituted double bond. When the concentration of the oxidant is low (DMDO is formed... 

The oxidation of allenylsulfonamides 75 is also possible by using DMDO [23], Unlike the corresponding reaction of allenyl acids, oxidation of allenyl sulfonamides usually cannot be stopped after the formation of the allene oxide 76 but proceeds further to the spirodiepoxide intermediate 77, finally giving hydroxypyrrolidinone 78 and hydroxypiperidone 79, respectively (Scheme 17.23). Similarly to y-allenyl alcohols, aldehydes and acids, five-membered heterocycles, e.g. 80, are also formed from y-allenylsulfonamides. In the latter case the reaction can be terminated after the first epoxidation by addition of p-toluenesulfonic acid. 

With this revision in our original plans, both alkenes and allenes were found to undergo efficient cycloadditions to produce cyclooctenone products in a new [6+2] cycloaddition process. This novel cycloaddition has been shown to proceed efficiently with alkenes tethered with sulfonamide, ether, or geminal diester Hnkers (Tab. 13.15, see page 294). Isomerization of the olefin, a potential competing reaction in this process, is not observed. Methyl substitution of either alkene in the substrate is well tolerated, resulting in the facile construction of quaternary centers. Of mechanistic importance, in some cases cycloheptene byproducts were isolated from [6+2] cycloaddition reactions in addition to the expected cyclooctenone products (that is, entries 3 and 4). 

The reaction of o-halobenzenesulfonamide 256 with allene 257, in the presence of Pd(0), affords the exocyclic alkene 258 via nitrogen attack on the 7t-allyl Pd-intermediate 259 (Scheme 35) <2001EJ0707>. The related cyclopropane product 260, formed in high yields in the analogous reactions of carboxamides, is not observed for the sulfonamide substrate 256. 

General Reaction Chemistry of Sulfonic Acids. Sulfonic acids may be used to produce sulfonic acid esters, which are derived from epoxides, olefins, alkynes, allenes, and ketenes, as shown in Figure 1 (10). Sulfonic acids may be converted to sulfonamides via reaction with an amine in the presence of phosphorus oxychloride [10025-87-3], POCl3 (11). Because sulfonic acids are generally not converted direcdy to sulfonamides, the reaction most likely involves a sulfonyl chloride intermediate. Phosphorus pentachloride [10026-13-8] and phosphorus pentabromide [7789-69-7] can be used to convert sulfonic acids to the corresponding sulfonyl halides (12,13). The conversion may also be accomplished by continuous electrolysis of thiols or disulfides in the presence of aqueous HQ [7647-01-0] (14) or by direct sulfonation with chlorosulfuric acid. Sulfonyl fluorides are typically prepared by direct sulfonation with fluorosulfuric acid [7789-21-1], or by reaction of the sulfonic acid or sulfonate with fluorosulfuric acid. Halogenation of sulfonic acids, which avoids production of a sulfonyl halide, can be achieved under oxidative halogenation conditions (15). 

Hydroamination of Allenes Different related amines can also be cyclized. The use of free amino groups led to long reaction times (several days), but sulfonamides, acetyl or BOc as protecting group led to fast conversion (in the latter case, problems of diastereoselectivity were observed). Optimization studies showed that, although cationic gold (I) complexes were not effective for these conversions, AuCI was a very good catalyst for these reactions. 

A new type of triaryl phosphine-functionalized imidazolium salt containing cations such as (6) has been prepared. Palladium complexes of (6) generated in situ have been used successfully in Heck-type reactions of aryl halides with acrylates and of 4-bromotoluene with styrene derivatives.34 The first Heck-type reaction of aryl halides with allenes has been reported. 1,3-Double arylations were observed with 3-substituted-l,2-allenyl sulfones, while 1-monoarylation was favoured with 3,3-disubstituted-l,2-allenyl sulfones.35 It has been shown that the a-arylation of methane-sulfonamides (7) may be achieved using palladium catalysis reaction proceeds through the sulfonamide enolates.36 It is also reported that palladium cross-coupling of alkynes with /V - (3 - i odophe n y I an i I i ncs) may lead to the formation of substituted carbazoles.37... 

The enantioselective hydroaminations of allenes with chiral phosphine catalysts was accomplished with substrates that had a terminal symmetric substitution and with the amines protected as carbamates or sulfonamides. The same symmetric substituents were necessary for the enantioselective transformation nsing chiral counterions. However, very recently, high enantiomeric excesses were reached with trisubstituted asymmetric allenes by a dynamic kinetic enantioselective hydroamination of allenyl carbamates (eqnation 110), even thongh the E/Z ratio of the prodncts was not optimal. 

Pyrroles can be synthesized from 3-pyrrolines 39 which can be prepared from a Crabbe reaction of propargyl sulfonamides 38 and selective cycloisomerization of the resulting allene intermediate. Subsequent oxidation of 3-pyrrohnes with 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) lead to 2-alkyl and aryl pyrroles 40 in this domino process (14EJO2305). 

Intriguing variable cyclization modes were also observed in the reaction of allenic epoxyalcohols with cationic gold catalysts (Scheme 4-99). Whereas substrates bearing a 6w-(phenylsulfonyl)methyl or sulfonamide group in the tether afforded mainly or exclusively the 7-exo-trig cyclization product, a very imusual 9-ent/o-trig cycloisomerization was observed with the corresponding malonate derivative. 

Toste has described the intramolecular enantioselective hydroamination of y- and 6-aUenyl sulfonamides catalyzed by enantiomerically pure bis(gold) phosphine complexes [42]. For example, treatment of the terminally-disubstituted y-allenyl sulfonamide 59 with a catalytic amount of [(R)-3,5-xylyl-binap](AuOPNB)2 (OPNB =p-nitrobenzoate) formed protected pyrrolidine 60 in 88% yield with 98% ee (Eq. (11.34)). Likewise, treatment of 6-allenyl sulfonamide 61 with a catalytic amount of [(JJ)-Cl-MeObiphep](AuOPNB)2 in nitromethane at 50 °C for 24h formed 2-alkenyl piperidine 62 in 70% isolated yield with 98% ee (Eq. (11.35)). Realization of high enantioselectivity in this protocol required employment of both a terminally disubstituted allene and a sulfonamide nucleophile. 

Reaction outcomes have been reported for 1,6-hexadiene (W=CH2, X=Br, I), diallyl sulfide (W=S, X=Br, I), diallyl ether (W=0, X=Br, diallyl sulfone (W=S02, X=Br, I), diallylmalonates [W=C(C02R)2, X=C1, Br, ], diallyl sulfonamide (W=N-Ts, X=C1, Br), and diallyl carboxyamide (W=N-C02R, X=C1, Br, ). Changing the steric and electronic character of the olefins can infiuence the regiochemical outcome in these systems. Less-substituted olefins (eq 3), electron-rich acetylenes (eq 4), and allenes (eq 5) react preferentially. Bis-allenic and 1,6-diyne systems also undergo radical cyclization. These factors are exemplified below. 

The similar addition to allenic tosyl sulfonamides produced the hromo allylic sulfonamides which were cyclized with potassium carhonate in DMF (eq 10). ... 

Hamid MHSA, Allen CL, Williams JMJ et al (2009) Ruthenium-catalyzed V-alkylation of amines and sulfonamides using borrowing hydrogen methodology. J Am Chem Soc 131(5) 1766-1774... 

The development of catalytic methods for the hydroamination of nonactivated alkenes, allenes, and alkynes has received considerable attention in recent years [1]. These highly atom-economical processes allow direct access to industrially and biologically relevant classes of compounds such as amines, enamines, and imines from cheap and readily available starting materials. This has recently led to an ever-increasing range of molecular compounds that have been identified as catalysts for these transformations (Scheme 13.1). Whereas rare-earth catalysts have been found to be mainly active in intramolecular hydroamination, other catalysts - in particular those of the late transition metals - are frequently limited to the addition of weakly basic substrates (aniline, sulfonamides, carboxamides, etc.) to alkenes, alkynes, and allenes. 

An interesting pathway towards the A-tosylated 3-trifluoromethylpyrrole 441 was developed by Rutjes et al. [ 144]. The palladium catalyzed addition of benzyloxy-allene 439 to sulfonamide 438 led to the A, 0-acetal 440 in excellent yield. Subsequent, treatment of 440 with the Grubbs II catalyst followed by acid workup gave the A-tosylpyrrole 441 in 80 % yield. 

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