Tosyl intramolecular

One such example is shown in Scheme 9, where intermediate 20 was swiftiy taken to 37 in a one-pot deprotection-tosylation-intramolecular y-alkylation mechanism utilizing tosyl fluoride. The resulting terminal olefin, when subject to Tsuji-Wacker oxidation conditions, furnished methyl ketone 38, which when exposed to strongly basic conditions triggered the Robinson annulation sequence, providing us with a cyclopentenone annulated analog 39. 

In a similar reaction the bis-tosylate shown below was to be converted into a bis-malonate derivative. In this cyclic derivative both groups are hold closely together and intramolecular reactions proved to be so much faster than intermolecular substitution under all ex-... 

Intermediate 37 can be transformed into ( )-thienamycin [( )-1)] through a sequence of reactions nearly identical to that presented in Scheme 3 (see 22— 1). Thus, exposure of /(-keto ester 37 to tosyl azide and triethylamine results in the facile formation of pure, crystalline diazo keto ester 4 in 65 % yield from 36 (see Scheme 5). Rhodium(n) acetate catalyzed decomposition of 4, followed by intramolecular insertion of the resultant carbene 3 into the proximal N-H bond, affords [3.2.0] bicyclic keto ester 2. Without purification, 2 is converted into enol phosphate 42 and thence into vinyl sulfide 23 (76% yield from 4).18 Finally, catalytic hydrogenation of 23 proceeds smoothly (90%) to afford ( )-thienamycin... 

Desulfonylation of dimethyl l-tosyl-l//-azepine-2,5-dicarboxylate 1 with Raney nickel in refluxing ethanol gives the intramolecularly hydrogen bonded dimethyl 1 //-azepine-2,5-dicar-boxy late (2), a rare example of a stable 1-unsubstituted 1//-azepine.12 2-Acetyl-1 //-azepine (75% mp 144 C) was obtained in a similar manner. 

The earliest method developed for the preparation of nonracemic aziridine-2-car-boxylates was the cyclization of naturally occurring (3-hydroxy-a-amino acid derivatives (serine or threonine) [4]. The (3-hydroxy group is normally activated as a tosyl or mesyl group, which is ideal for an intramolecular SN2 displacement. The cyclization has been developed in both one-pot and stepwise fashion [4—9]. As an example, serine ester 3 (Scheme 3.2) was treated with tosyl chloride in the presence of triethylamine to afford aziridine-2-carboxylate 4 in 71% yield [9]. Cyclization of a-hydroxy- 3-amino esters to aziridine-2-carboxylates under similar conditions has also been described [10]. 

A highly efficient construction of the steroidal skeleton 166 is reported by Kametani and coworkers111 in the intramolecular Diels-Alder reaction of the a, jS-unsaturated sulfone moiety of 165 (equation 117). Thus, when the sulfone 165 is heated in 1,2-dichlorobenzene for 6h, the steroidal compound 166 can be obtained in 62% yield. The compound 166 produces estrone (167) by elimination of benzenesulfinic acid and subsequent hydrogenation of the formed double bond. The stereoselectivity of the addition reflects a transition state in which the p-tosyl group occupies the exo position to minimize the steric repulsion between methyl and t-butoxy groups and the o-quinodimethane group as shown in equation 117. 

The intramolecular cycloaddition has proven to be the method of choice for the preparation of steroids. A diastereomeric mixture of 204, prepared from 191 and tosylate 203 has been cleanly converted to dl-estra-1,3,5(10)-trien-17-one (205) in 85% yield (equation 130). A second example of the intramolecular cycloaddition reaction is the formation of the cycloadduct (209), the key intermediate in a synthesis of the As-pidosperma alkaloid aspidospermine, upon heating 208 at 600 °C (equation 131)124. The sulfone 208 can be prepared by reaction of 3-ethyl-3,4,5,6-tetrahydropyridine (206) with the acid chloride 207. 

The reaction can be done intramolecularly. N-Benzyl pent-4-ynamide reacted with tetrabutylammonium fluoride to an alkylidene lactam. Similar addition of a tosylamide-alkene, with a palladium catalyst, led to a vinyl Al-tosyl pyrrolidine. Similar cyclization reactions occur with tosylamide-alkynes. ... 

A stmple and general synthesis of 2,2,4,5-tetrasubstituted furan-3(2//)-ones from 4-hydroxyalk-2-ynones and alkyl halides via tandem CO, addition-elimination protocol is described <96S 1431>. Palladiuni-mediated intramolecular cyclization of substituted pentynoic adds offers a new route to y-arylidenebutyrolactones <96TL1429>. The first total synthesis of (-)-goniofupyrone 39 was reported. Constmction of the dioxabicyclo[4.3.0]nonenone skeleton was achieved by tosylation of an allylic hydroxy group, followed by exposure to TBAF-HF <96TL5389>. 

The synthesis was carried out as shown in Scheme 13.24. A diol was formed and selectively tosylated at the secondary hydroxy group (Step A-4). Base then promoted the skeletal rearrangement in Step B-l by a pinacol rearrangement corresponding to 23-11 => 23-III in the retrosynthesis. The key intramolecular Michael addition was accomplished using triethylamine under high-temperature conditions. 

Chapter 1 deals with alkylation of carbon nucleophiles by alkyl halides and tosylates. We discuss the major factors affecting stereoselectivity in both cyclic and acyclic compounds and consider intramolecular alkylation and the use of chiral auxiliaries. 

In order to synthesize quinolizidine compounds, some authors have used the Parsons method (Bu3SnH/AIBN) to cleave the iV-tosyl group of 2-piperidones such as 144 (AIBN = 2,2 -azobisisobutyronitrile). After detosylation to 145, the intramolecular cyclization of the lactam promoted by sodium hydride gave quinolizidinone 146. T reatment of this compound with Raney nickel both cleaved the C-S bond and reduced the C=C bond to give quinazolinone 147, while the lactam carbonyl was reduced with LiAlH4 to give 148 (Scheme 23) <2005TL8551>. 

Izquierdo et al. reported the enantioselective synthesis of 5-O-methylthioswainsonine 53 from a derivative a d-glucose as a single stereoisomer. Intramolecular alkylation of the tosylate precursor 52 created the bicyclic system in the final step of the synthesis as outlined in Equation (17) <1996TA2567>. 

While nitrogen sources such as chloramine-T and PhI=NTs have been used for aziridination reactions, TsNC12 has not been explored until now. The reaction of TsNCL, with Pd(OAc)2 and K2C03 provides the expected N-tosyl aziridines in good yields <06TL7225>. This reaction presumably proceeds through an initial amidohalogenation reaction catalyzed by palladium. The chloroamide is then converted to the aziridine via an intramolecular substitution reaction. 

When a solution of phenacyl halide 258 and excess tosyl hydrazide in methanol is heated to reflux, l-(tosylamido)-4-aryltriazole 261 is formed. The reaction proceeds presumably via dihydrazide derivative 259 that subsequently undergoes intramolecular cyclocondensation to triazoline 260. In the following step, the triazoline must be oxidized to the final triazole product 261. Mechanism of the oxidation is not quite clear, but the probable oxidant is the starting phenacyl halide, as a half of it is converted to the corresponding acetophenone tosylhydrazone that is isolated as the main side product of the reaction (Scheme 37) <2004H(63)1175>. 

These workers also synthesized tryptamine stannane 161 and effected Stille couplings with this compound, including the intramolecular reaction 162 to 163 [171]. Eight- and 9-membered rings could also be fashioned in this manner. Other Pd catalysts were much less successful. The N-tosyl derivative of 162 was similarly prepared and used in Stille chemistry. 

Katritzky et al. <1997JOC4148> described the cyclization of pyrrole derivatives 133 via lithiation at the benzotriazol-1-ylmethyl group and subsequent intramolecular nucleophilic displacement of tosylate to give in good yields dihydropyrrolizines 65, which lead to 3/7-dihydropyrrolizines 68 under treatment with malonate anion (see Section 11.01.5.3). 

Aminopyrazoles 257 substituted at the C-4 and C-5 positions react with a variety of imidate hydrochlorides giving iV-hydroxyamidines 258, that after tosylation and intramolecular cyclization afford the corresponding pyrazolo[ 1,5-4 )-[l,2,4]triazole derivatives 259 (Scheme 21) <1998CPB287, 1998CPB69>. 

Also, the intramolecular [3+2] cycloaddition approach can be used to generate several tricyclic ring systems 66-68 when the azide and the cyanamide functionalities are bonded to a carbocyclic ring <20010L4091> (Scheme 14). The relative stereochemistry of the starting materials is preserved in the products. While the yield of the m-fused 5-5-6 tricyclic ring system 66 is very high, the yield of the trans-fuseA products 67 and 68 is considerably lower as expected based on the unfavorable conformation for the cycloaddition process. The even lower yield for the tosylated and therefore activated derivative 68 was rationalized by its decreased thermal stability. 

N-Tosyl amides and lactams.2 DCC in combination with 4-pyrrolidinopyri-dine (4-PPy) effects condensation of carboxylic acids with secondary sulfonamides to provide N-tosyl amides in 75-90% yield. The intramolecular version of this reaction provides 4-, 5-, and 6-membered N-tosyl lactams in 60-90% yield. 

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