Acyl tosylates intramolecular

She and co-workers took advantage of the acyl anion equivalent formed from the addition of an NHC to an aldehyde to catalyze the formation of benzopyranones via an intramolecular S 2 displacement (Scheme 50) [167], Various aromatic aldehydes provide alkylation products in moderate yields when the leaving group is either tosylate or iodide. No reaction was observed when phenyl or methyl was placed alpha to the leaving group. 

Benzenium ions (199 X = acyl) on treatment with p-TSA in toluene undergo intramolecular O-alkylation to give the oxazolines (201 X=acyl Scheme 18, path b), rather than ring expansion to the lH-azepine as mentioned earlier for the N-tosyl derivative (Scheme 18, path a). However, these oxazolines are thermally labile and on heating at 180 °C rearrange in high yields (84-93%) to 1-acyl-1//-azepines (200 X = ArCO or Ac) <81AG(E)699>. 

Construction of a nitrogen six-membered heteroring may be achieved by intramolecular C-acylation. This pathway was used, for instance, in the synthesis of l//-naphtho[hc]pyridine-2,3-dione 329 from N-tosyl-N-(a-naphthyl)aminooxallyl chloride 328 (28USP1698894). Approaches to 1H-... 

Whereas intramolecular acylation of indole 88 takes place only in moderate yield, the analogous alkylation of indole 101 gives the dihydrodibenzpyrrol-izine (102) in excellent yield. The reaction conditions for conversion of acid 88 to the tosylate (101) are, however, critical.23 A conversion of tosylate 103 to dihydropyrrolizine 104 was reported.69... 

A separate study of the alkylations of 1 has been reported by Oppolzer and co-workers. The group has employed LDA, LiTMP, and n-C4Hs,Li to metalate 1. The resulting anion condenses with a variety of electrophiles (primary alkyl bromides, iodides, tosylates, disulfides, and acyl derivatives) to afford the corresponding monosubstituted derivatives in 30-95% yield. If the alkyl group contains a double bond in the 4- or 5-position, polycyclic compounds are prepared by thermal extrusion of SO2 followed by intramolecular Diels-Alder cyclization. 

AT-Acylated 0-tosylhydroxyproline derivatives (CXLVIII) are known to undergo intramolecular displacement of 0-tosylate anion by the carboxylate anion under mild conditions leading to iNT-acylated lactones of allohydroxy-proline (CXLIX) (Patchett and Witkop, 1957). 

The application of this intramolecular displacement principle to amides and peptides of JV-acylated 0-tosyl- or 0-mesylhydrox5T)roline derivatives (CL) has not met with success so far (Francis and Witkop, unpublished... 

Under the same basic conditions /ra . -l-acetoxymethyl-1-methyl-2-tosylcyclopropane generated an a-sulfonyl anion, which attacked the ester group intramolecularly and afforded 2,5-dimethyl-l-tosyl-3-oxabicyclo[3.1.0]hexan-2-ol (22) in 50% yield.Stereoselective synthesis with a chiral cyclopropyl sulfoxide was experienced when ( )-4-tolylsulfinylcyclopropane was reacted first with butyllithium and then with methyl benzoate and gave 1-benzoyl-1-[(5)-4-tolylsulfinyl]cyclopropane (23a) in 62% yield. A useful reaction took place when 2-(hy-droxymethyl)cyclopropyl phenyl sulfide was treated first with an excess of butyllithium and then with dimethylformamide and gave 2-hydroxy-l-phenylsulfanyl-3-oxabicyclo[3.1.0]hexane (24), a lactol which has been used to carry out various useful synthetic transformations. Another useful reaction occurred when cyclopropyl phenyl sulfones were treated with butyllithium followed by an acyl imidazole to give acyl cyclopropanes in decent yield. 

Another approach to cephalotaxine intermediate 43 was reported by Weinstein and Craig (65) in 1976 (Scheme 33). The reaction of 3,4-(methy-lenedioxy)-iS-phenethyl tosylate (191), a derivative of the previously used nosylate 117, and sodium 2-carboethoxypyrrole (192), followed by hydrolysis, produced the carboxylic add 193. Intramolecular Friedel-Crafts acylation of 193 with stannic chloride and trifluoroacetic anhydride yielded the benzazepine 194, which was reduced, hydrogenated, and finally oxidized to produce the tricyclic Dolby-Weinreb enamine 43. 

One of the major problems encountered in this synthesis is the difficulty of obtaining the starting materials (either the a-aminocarbonyl compounds or their acylated derivatives). The former may be prepared by Neber rearrangement of ketoxime tosylates with a base such as ethoxide or pyridine.46 a-Acylamino carbonyl compounds can be prepared directly by the reductive acetylation of oximino ketones.28 38 Balaban and his collaborators47-60 have developed an excellent method for the synthesis of a-acylamino ketones (5). They are obtained in yields of 50-90% by the reaction of azlactones (2-aryl-5-oxazolone, 4) with aromatic hydrocarbons in the presence of aluminum chloride under Friedel-Crafts conditions the reaction may proceed either intermolecularly or intramolecularly. 

An example of intramolecular ring-forming release is shown in eq 12.11 Amino alcohols 10 were 7V-acylated with acid chlorides and the crude product was loaded onto PS-TsCl. Base-promoted, ring-forming displacement of the tosylate released the oxazolines into solution. Ring-forming release of a sulfonate linker has also been utilized with a Multipin system, l ... 

Indoles are also accessed by intramolecular cyclization of azides, -acyl, or JV-tosyl anilines with alkynes (eqs 25-28). 

---