Lactone formation in superacidic media

Abstract

The reaction of substituted 1 -hydroxycyclohexanecarboxylic acids in fluorosulphuric acid has been studied. Cyclisation takes place around 0 "C, accompanied by rearrangement in appropriate cases, yielding the thermodynamically stable lactone or mixture of lactones. An unexpected feature of these reactions is that the carboxy-substituted cyclohexyl carbocation does not undergo ring contraction, unlike the unsubstituted cyclohexyl carbocation, although the cycloheptyl system contracts to cyclohexyl. We suggest that the cyclohexyl carbocation is strongly stabilised by carboxyl substitution, as a result of through-space interaction between the carboxyl oxygen atom and the carbocation centre.Superacidic media have long been recognised as ideal for carrying out cyclisation reactions.' Over the past decade, the method has been applied widely to obtain homocyclic and heterocyclic systems.2 The work of Sorensen on methylated linalools showed that the relative rates of competing methyl shift and carbocyclisation reactions were similar in superacidic and in normal acid media. The emphasis on cyclisation in superacids results from supression of competing reactions with external nucleophiles and elimination reactions; this allows intramolecular reaction of the carbocation with an internal nucleophile to dominate, yielding a cyclic product. Such a process usually yields the thermodynamically stable product, since the carbocation has a long lifetime under these conditions, and solvation by the counterion lowers barriers to rearrangement., Lactones should be readily accessible by this route, but the reaction has generally been ignored, except for formation in solution of the lactone of bicyclo[3.1.0] hex-2-ene-endo-6-carboxylic acid.4 We have, therefore, investigated the preparation of lactones in superacidic conditions, starting with a simple example, cyclohexanecarboxylic acid 1,4-lactone (1). Our experience of superacid reactions has been that the carbocation centre is relatively mobile, so that in this case a carbocation generated at any convenient position should migrate to give the stable 1,4-lactone. We therefore took the readily accessible 1 -hydroxycyclohexanecarboxylic acid (2), and dissolved it in FS0,H-SO, at -70 "C. The 13C n.m.r. spectrum showed only the presence of the protonated acid. On warming the solution to 0 "C overnight, and then adding fresh SO, and running the spectrum at -70 "C, the presence of the lactone (1) was detected. Quenching the reaction mixture in alkaline aqueous methanol gave the lactone as a crystalline solid, whose identity was confirmed conventionally. +OHMigration of the carbocation from C-1 to C-4 could take place either directly in a 1,4-shift, or by a combination of 1,2-and possibly 1,3-shifts. To distinguish between the possibilities, we repeated the experiment on a sample of (2) which had been fully deuteriated on C-2 and C-6. The deuteriated sample in FS0,H-SO, at -70°C gave a spectrum similar to that of the undeuteriated acid in similar conditions except for loss of the C-2 peaks. ...

Molecular rearrangements of superelectrophiles

“…Whittaker and Carr have described a series of superacid-promoted reactions to prepare bicyclic lactones [ 28 ]. Several of the conversions involve superelectrophilic rearrangements.…”

“…Several studies have examined this question using deuterium-labeled superelectrophiles. Reaction of 1-hydroxycyclohexanecarboxylic acid ( 137 ) in FSO 3 H and SO 3 at −70 °C, followed by warming to 0 °C, gives a clean conversion to the protonated bicyclic lactone 140 ( Scheme 28 ) [ 28 ]. A mechanism is proposed which involves ionization to the superelectrophile 138 , followed by successive hydride shifts to give the charge separated dication 139 .…”

Carbocations in Superacid Systems

“…(3.71)]. Protonated lactones may be prepared by direct protonation 582 or by protonating hyroxycarboxylic acids 583 [Eq. Experimental evidence and theoretical data indicated that the strained cubyl system effectively stabilizes the carbocationic centers through CÀC bond hyperconjugation (283).…”