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《有机化学》课程教学资源（文献资料）Rearrangement of 1,2-Glycols, Halohydrins, and Azidohydrins

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VOLUME 41, NUMBER 14 0 Copyri ht 1976 by the American 8hemical Society JULY 9,1976 Molecular Rearrangements with Ethoxycarbonyl Group Migrations. 2. Rearrangement of 1,2-Glycols, Halohydrins, and Azidohydrins1*2 ,Jacques Kagan,' Dalmacio A. Agdeppa, Jr., David A. Mayers, S. P. Singh, Mary J. Walters, and Richard D. Wintermute Chemistry Department, University of Illinois, P.O. Box 4348, Chicago, Illinois 60680 Received September 29,1975 The ethoxycarbonyl group has been shown to undergo a facile 1,2 migration during the pinacol rearrangement of glyceric esters in fluorosulfonic acid. Pyruvic esters and 2-hydroxy-3-butenoic esters were also formed, and the prolonged treatment of some pyruvic esters in fluorosulfonic acid led to their isomerization into p-keto esters. The product of ethoxycarbonyl group migration was also found in the treatment of an azidohydrin with nitrosonium tetrafluoroborate, and that of halohydrins with silver salts. The rearrangement of tert- butyl 2-hydroxy-3-chloro- 3-phenylbutyrate (24) without fragmentation upon treatment with silver carbonate argued against a mechanism involving a carboxylium ion, and in favor of a process in which the alkoxycarbonyl moiety acts as an internal nucleophiie. The migration of a carboethoxyl group in preference to hydrogen, alkyl, or aryl groups in the well-known pinacol rearrangement has not been previously noted,3 but we were encouraged to look for it by its discovery in the acid-catalyzed isomerization of epoxides.ll4 Glyceric esters 1, obtained by mild hydrolysis of glycidic esters (I) or by hydroxylation of OH OH II - COOEt Ph-C-C-COOEt Ph -7 - 7 II R I he k ke R I 1 COOEt I OH I -CCKOOEt Ph-C-COR Ph-C-C-COOEt II I CH, R 2 3 4 I ph-(i Me Me Ph-C-C-COOEt 5 6 bR=H m,R=Me e,R=Et f,R = Ph cinnamic esters, were treated with sulfuric acid, alone or in acetic acid, trifluoroacetic acid, or boron trifluoride, with poor results. For example, treatment of lm with sulfuric acid in acetic acid yielded the allylic alcohol 4m with only minor amounts of 3-phenyl-2-butanone and of the desired rearrangement product 3m. Fluorosulfonic acid used as solvent was found to be a most convenient catalyst for the desired pinacol rearrangement, and the standard procedure in this work consisted in dissolving 1 in pure fluorosulfonic acid, both having been precooled to 0 "C, pouring the reaction mixture over ice after 3 min at this temperature, and extracting with carbon tetrachloride. The crude extract was free from starting material. The experimental results, presented in Table I, were very reproducible. They were generally similar to those obtained in the reaction of the related glycidic esters with boron trifluoride,ls4 and the same sequence of apparent migratory aptitudes was deduced. The allylic alcohols 3 were not detected, but independent treatment of 4m, 4e, and 4f under the reaction conditions confirmed their reactivity and their partial conversion into the lactones 5m and 5e and the indene 6, respectively. The synthesis of indenes from phenyl substituted allylic cations has been previously de~cribed.~ The intramolecular Friedel-Crafts reaction requires the allylic-benzylic cation to have the geometry shown in E-7. Whether or not the.other E-7 2-7 isomer was formed was not established directly. The observed cyclization to 6 from each diastereoisomer of If in the presence of boron trifluoride agreed with a facile interconversion of both cation^,^ but the absence of the lactone 5f indicated a slow rate of cyclization from 2-7. Note that the indene 6 had not been observed in the boron trifluoride catalyzed rear- 2355

2356 J. Org. Chem., Vol. 41, No. 14,1976 Kagan, Agdeppa, Mayers, Singh, Walters, and Wintermute Table I. Pinacol Rearrangement of Glyceric Esters with FSOIH at 0 "C for 3 min (Yields from NMR Analyses) % products Precursor 2 3 5 Others lh u 6.5 a U lm b 84 16 (threo + threo- lm b 84 16 erythro- lm b 84 16 lm-ds b 90 10 (threo + le (threo + 9 75 9 If (threo + 60 13 6 (12),8 (6),9 (9) erythro) erythro) erythro) erythro) Too complex for analysis. Trace. rangement of If, which yielded a single product, resulting from phenyl group migration, further indicating that 4f was not formed under the conditions of that reacti0n.l The dehydration of both isomers of 1m into an almost single rearranged product 3m (Table I) contrasted with the results of the boron trifluoride treatment of Im, from which the three rearranged products 2m, 3m, and 4m were 0btained.l However, the isomerization of lm into the allylic alcohol was the preferred process in weaker acids, such as trifluoroacetic or dilute fluorosulfonic acids, and the treatment of Im with pure fluorosulfonic acid under conditions identical with those used with lm gave a somewhat different product distribution, 52% of 3m, 48% of 5m, and a trace of 2m. The migration of the phenyl group from the 3 to the 2 position would also have given 3m from lm, but this process was ruled out by the study of lm-3-methyl-d~, which yielded 3m-d3 with no deuterium at the acetyl position, a result which agrees with the behavior of 1m.l The acid treatment of If yielded two unexpected products, ethyl 2,2-diphenylacetoacetate (8) and acetophenone (9), along with 2f, 3f, and 6 (Table I). This reaction contrasted with that of If with boron trifluoride, which yielded only 2f,2 and where the allylic alcohol 4f could not have been an intermediate, since its treatment with boron trifluoride yielded the indene 6 as the sole product. Shorter reaction times did not have a marked effect on the yield of 9, but reduced the formation of 8, and these studies also demonstrated the very fast rate of this pinacol rearrangement, which was complete in less than 15 s at -5 "C and where only 6% of starting material was left after 15 s at -50 "C. The formation of acetophenone described above must have taken place in the reaction of the starting material, since the reaction products did not yield it when submitted to the treatment with fluorosulfonic acid. The idea that an air oxidation reaction had taken place, formally the reverse of a pinacol synthesis, was dismissed by checking that bubbling air through a solution of If did not lead to any detectable fragmentation. The most reasonable mechanism for the fragmentation of glyceric esters into carbonyl products involves a protonation at the ester carbonyl, followed by a retro-aldol cleavage reaction. This type of acid-catalyzed /3 fission had not 07H RZ II + PhCOR, + R2-CH-COOEt I R3 Table 11. Isomerization of 2f Catalyzed by FSOBH at 0 "C -_ I_ Time, min 2f 3f 8 5 79 15 6 10 71 21 8 20 50 33 17 40 28 50 22 80 16 57 27 120 8 64 28 150 5 65 30 180 2 71 27 210 0 71 29 Table 111. Isomerization of 2m Catalyzed by FSO3H at 0 "C Time, min 2m 3m I1 3 95 3 2 90 48 32 20 180 19 46 35 300 5 55 40 450 0 56 44 been previously reported with esters, although it was known for carboxylic acids6 and ketone^.^ We also found that 2,3- diphenyl-3-hydroxybutyric acid yielded acetophenone and methyl phenylacetate upon attempted esterification with methanol catalyzed by sulfuric acid. However, a control experiment disclosed that fragmentation had taken place prior to exterification, since the ester formed by reaction with diazomethane did not undergo the fragmentation reaction when it was treated in the same acidic conditions. We previously reported on the acid-catalyzed formation of benzophenone from ethyl 3,3-diphenylpyruvate, which we tentatively ascribed to a retro-pinacol rearrangement to a glyceric ester, followed by the above fi fission.8 Later work on the rearrangement of chlorohydrins, which also led to fission? attracted our attention to the facile autoxidation of ethyl 3- phenylpyruvates, a reaction which best explains the formation of 9 in this case. In the effort to establish whether acetophenone had been formed by reaction of the starting material or of the reaction products, 2f was treated in the usual reaction conditions. To our surprise, it was converted into two other products, and acetophenone was not formed (Table 11). These two products were purified by preparative TLC and identified as 3f and 8, the @-keto esters isomeric with 2f, which were also observed in the direct reaction of If. Ph,-C - COCOOEt I Me 2f Ph Ph - FSOjH I I PhCO-C-COOEt + MeCO-C-COOEt I Ph I Me 3f 8 We do not know the exact mechanism of the a-keto to 6- keto ester rearrangement, for which there are at least two alternatives, differing by whether or not the ethoxycarbonyl group migrates,8 and we still hope to see this problem elucidated in the near future, by studying the rearrangement of properly labeled precursors. The generality of the fluorosulfonic acid catalyzed rearrangement of a-keto to @-keto esters has not been fully established, but we found that 2m [the main product formed in

Rearrangement of 1,2-Glycols, Halohydrins, and Azidohydrins J. Org. Chem., Vol. 41, No. 14,1976 2357 Table IV. Solvolysis of 17 Solvent Temp,OC Time,h Agsalt Ih 2h 3h 4h lh 17 Other None 132 22 None 50 50 Nonea 132 63 None 100 None 132 63 None 25 44 50% EtOH r.t. MeOH r.t. 4 Nitrate C6H6 r.t. 21 Carbonate 60 5 14 18 Acetone r.t. 21 Carbonate 70 10 14 5 MezSO rat. 21 Carbonate 17 3 HMPTA rat. 21 Carbonate c c0 b CCll r.t. 41 Carbonate 68 2 19 11 THF rat. 41 Carbonate 35 2 10 3 CH3CN r.t. 41 Carbonate 80 2 16 2 Hexanes r.t. 65 Carbonate 50 2 28 20 Ether r.t. 65 Carbonate 25 5 9 20 MezSO r.t. 96 Carbonate c co c DMF r.t. 96 Carbonate c cb C 88% HCOOH ' r.t. 16 None AcOH r.t. 16 None AcOH 118 16 None 50 Ether -10 1.5 Triflate 100 Ether 0 2 Tosylate C6H6 ret. 20 Tosylate C c 0 29 C6H6 r.t. 46 Mesylate 80 a In the absence of air. Detected by NMR. Mixture too complex for NMR analysis. the acid treat:ment of ethyl 2-phenyl-3,3-dimethylglycerate (lo)] did rearrange to yield the isomeric P-keto esters 3m and 11 (Table 111). OH OH II I MezC-C-COOEt -+ Me&-COCOOEt I Ph Ph 10 2m Me I Me I -+ MeCO-C-COOEt + PhCO-C-COOEt I I Ph 3m Me 11 Finally, in ,the course of this work glyceric esters having different subetitution patterns at the 3 position were also treated with fluorosulfonic acid, and the results are shown here: COOEt I I R1 OH OH R, II I II I R1 R2 PhC-CCOOEt - PhCCOCOOEt + PhCCOR, + PhCOR1 R, 12,R,=Ph;Rp==H 88% 0 12% 13, R, = H, R, = Me 0 low0 0 14,Rl=H;R,=Ph 95% 0 5% Ethoxycarbonyl Group Migration from an Azidohydrin Precursor. Following the report of easy generation of carbonium ions by the nitrosonium tetrafluoroborate decomposition of azides,1° the procedure was utilized with ethyl 2-hydroxy-3-azido-3-phenylbutyrate (E), which was readily obtained by treating Ih with hydrazoic acid. N, I "2 I Ph- C- CHOHCOOEt Ph- C- CHOHCOOEt I I 9 (Tr) 9 (31) 23 (100) 22 (100) 4 80 C bc 50 40 C C C C 100 100 AcO-4h (50) 100 0 C 14 14 (6) There was no reaction when 15 was treated with an excess of the salt at room temperature in acetonitrile, benzene, or dimethoxyethane for up to 60 h. The starting material disappeared completely upon refluxing for 6 h in benzene, and the product of ethoxycarbonyl migration was detected in 18% yield, along with a trace of 2h and 10% of the allylic alcohol 4h. Acid-catalyzed decarbonylation and condensation reactions were probably responsible for the low yield of identified products, a situation similar to that observed with Ihl and lh. The identification of 3h in this reaction mixture was sufficient proof that the ethoxycarbonyl grohp could migrate when the azohydrin was used in the generation of the initial cation, and no further work was devoted to this reaction. The synthesis of the amino alcohol 16 proved to be much more difficult than anticipated.ll The treatment of the epoxide Ih with ammonia or sodamide did not yield 16. Ring opening took place when Ih was treated with benzylmine, but the nitrogen was then doubly benzylic, and the hydrogenolysis cleaved the bond between the nitrogen and the adjacent tertiary carbon, rather than the desired one. Acid-catalyzed reactions, such as the condensation with a nitrile to form the required carbon-nitrogen bond, instead resulted in the dehydration into 3h. The reduction of 15 with sodium borohydride gave a low yield of 16, which was purified with difficulty. Upon diazotization of this product with isoamyl nitrite, a very complex mixture was generated, where 3h was absent as judged by NMR. Further work in this area will have to await the development of a convenient synthesis for 16. Ethoxycarbonyl Group Migrations from Halohydrins. Because of the ease with which the product of rearrangement with ethoxycarbonyl group migration could be detected by the NMR analysis of the aldehyde proton, much work was devoted to the chlorohydrin 17, derived from Ih by treatment with hydrogen chloride in ether, and which was a 1:l mixture of diastereoisomers. The solvolysis of 17 in 88% formic acid at room temperature for 16 h resulted in hydrolysis to the glyceric ester lh. No reaction was observed under the same conditions in acetic acid, but following reflux in this latter solvent for 16 h, the allylic alcohol 4h and its acetate were formed in equal amounts. Me 15 Me 16

2358 J. Org. Chem., Vol. 41, No. 14,1976 Kagan, Agdeppa, Mayers, Singh, Walters, and Wintermute Table V. Dehydrochlorination of 20 and 21 in the Presence of Silver Carbonate Compd Solvent Time, h Temp, "C COOCzHh migr Epoxide Starting material Others 20 C6H6 Ether DMF DMF CHsCN CHsCN Acetone 21 DMF C6H6 15.5 16 15 40 15.5 24 15 66 16 65 8 r.t. a r.t. 0 15 r.t. 82 r.t. a 68 r.t. 0 a Identified by NMR, but spectrum too complex for analysis. The reaction of 17 was then carried out in a variety of solvents. Nucleophilic displacement of the chloride, but no rearrangement, was the rule in hydroxylic solvents. In aprotic CI I I Ph-C-CHOHCOOEt Me 17 X OH II I II Ph- CH- C - COOEt Ph- C-C- COOEt Me Me Me 18, x = ci 20, X = Rr 22,X = OMe 23,X=OEt 19, x = C1 21, X = Br solvents, the dehydrochlorination took place in all possible manners, yielding the allylic alcohol and the epoxide as well as the products of molecular rearrangement, the a-keto ester 2h, and the aldehyde 3h. Qualitative variations in the product distribution were observed as a function of the solvent chosen, and they are recorded in Table IV. The nature of the silver salt used also had an effect on the product distribution, and no 3h was detected with silver tosylate, mesylate, or triflate. After this series of experiments was completed, silver carbonate was utilized with other halohydrins, in order to ensure that no strong Bronsted acidity would be developed during the course of the reaction, thereby ensuring that the migration of the ethoxycarbonyl group would not actually involve a protonated ester moiety. No reaction was observed at room temperature with the chlorohydrins 18 and 19, but the corresponding bromohydrins 20 and 21 did undergo dehydrobromination in these conditions, yielding the epoxide and the product of ethoxycarbonyl group migration in each case, as well as the allylic alcohol in the case of 21 (Table V).12 These observations confirmed the preference for the migration of the ethoxycarbonyl group over the methyl which was previously encountered in the rearrangement of glyceric and glycidic esters under certain conditions. Much more work remains to be done to correlate the effect of the temperature and the stereochemistry of starting materials with the product composition. However, the present results are in line with those described for the rearrangement of the corresponding glycidic esters. The allylic alcohol 4 was the major product at low temperature. In the absence of electrophilic assistance, the product of methyl migration 2h was formed next, and the formation of the product of ethoxycarbonyl migration 3h, which has the highest activation energy, required electrophilic assistance. 61 31 a a a a 100 a a 100 100 a 0 4m (100) 4m,a 5mn Conclusion The simplest explanation for the pinacol and pinacol-like rearrangements described in this work starts with an ionization at the 3 position. We have no information yet on the lifetime of the 3-carbonium ion generated, compared to the rate of the subsequent migration of one group from the 2 to the 3 position, but it is anticipated to depend on the reaction conditions. The concertedness reported in other pinacol rearrangement~,~~ and the recently disclosed concerted rearrangement of the epoxide Ih to 3h,14 suggest that a group migration from the 2 to the 3 position could well take place synchronously with the departure of the leaving group, resulting in inversion of configuration at the 3 position. Formally, a distinction may be established between a process in which the carbonyl carbon remains with eight electrons throughout (path A) and that in which the bonding electrons are first attracted to the adjacent electron-deficient site (written here as a full cation for convenience), yielding an enol-carboxylium ion pair, which further undergoes the acylation reaction required by the structure of the final product (path B). P "-YF= Me OY Path A +I PathB Ph-C C COOR' + IV Me R - Ph-C=C-OY + C-OR' II 0 II Me R The fact that all the attempted syntheses of carboxylium ions have resulted in their decomposition with loss of carbon dioxide15 gave a strong presumption against path B. Additional support for this view was derived from the study of tert-butyl 2-hydroxy-3-chloro-3-phenylbutyrate (241, which was treated with silver carbonate in benzene. If path B had been operative, decomposition to carbon dioxide and isobutene would have been expected. Instead, the rearrangement with ester group migration was observed, indicating that little or no positive charge was generated at the ester carbonyl, and that the carbon-carbon bonding electrons act as an internal nucleophile in the rearrangement. Each diastereoisomer of 24 was treated under the same conditions. Although they yielded the same products, 25,26, and 27, considerable stereoselectivity was displayed and one isomer gave predominantly the aldehyde resulting from ester group migration (ca. 50% of the products) with only 25% of epoxide, while the other gave only 33% of this aldehyde and

Rearrangement of 1,2-Glycols, Halohydrins, and Azidohydrins J. Org. Chem., Vol. 41, No. 14,1976 2359 C1 OH COOCMe, I1 I Ph-()-$-COOMe3 - Ph-c-CHO II Me H I Me 24 25 OH I + Ph-C-CH-COOMe3 + Ph-C-CHCOOMe3 II I CH* Me Ph- CH- CHO 26 27 I Me 28 56% of the diaotereomeric epoxide (27). The formation of acetophenone in these dehydrochlorination reactions is interpreted as resulting from the autoxidation of tert- butyl 2- keto-3-phenylbutyrate: giving a measure of the extent of hydrogen migration from the 2 to the 3 position. In contrast, the treatment of 27 with boron trifluoride in benzene resulted in complete cleavage to 2-phenylpropionaldehyde (28), coupled with the alkylation of the solvent, a decomposition reaction reminiscent of the thermal process.16 Although further work is obviously needed, the ability of the alkoxycarbonyl group to undergo 1,2 migrations in a variety of pinacol-like rearrangements is now firmly established. The ready availability of glycidic and glyceric esters, as well as chlorohydrins, suggests that the introduction of a carboxylic ester function adjacent to a carbonyl group via a pinacol-like rearrangement may occasionally compete with current methods based on nucleophilic reactions of enolate ions. From the practical viewpoint, a competition between two different substituents is usually the rule for the migration from the carbinol to the adjacent cationic position in these rearrangements. We previously demonstrated that a judicious choice of the reaction parameters often provided an effective control over the formation of the primary products.l Some selectivity over the subsequent isomerization of these products is also available, and may even lead to products not directly accessible from the starting material, such as 8 from If. Further work will be directed at gaining a more effective control over the selection of the group which migrates in these competitive rearrangement reactions. Experimental Section Rearrangement of Ethyl 3-Methyl-3-phenylglycerate (lh). Fluorosulfonic acid (1 ml) precooled to 0 OC was added dropwise with stirring to 472 mg of the diastereoisomer of lh melting at 93-94 OC.1' The reaction mixture was stirred for 3 min and poured onto an icewater-carbon tetrachloride mixture. After separating the organic layer and extracting the aqueous phase twice with 50 ml of Cc4, the com- bined organic layers were washed with two 50-ml portions of 5% NaHC03, dried, and concentrated. The NMR (CC14) was very complex, but showed the aldehyde signal of 3h at 9.90 ppm. Preparative TLC on silica gel, developed successively with EtOAc-petroleum ether (1:9) and EtOAc-CCL (1:9), led to many overlapping bands. The only product isolated in pure form was ethyl 2-formyl-2-phenylpropionate (3h, 20 mg), identical with an authentic sample. The same results were observed when either the lower melting or a mixture of both diastereoisomers of 111 was treated as above. Ethyl 2,3-Dixnethyl-3-phenylglycerate (lm). The hydration of 2.0 g of Im with 30% by weight of perchloric acid in 50% aqueous THF for 16 h at room temperature led, after workup, to 1.5 g of lm, as a viscous oil which was purified by chromatography over silica gel. A mixture of both diastereoisomers was obtained NMR (CDCl3) 7.0-7.6 (br, 5 H), 4.07 ((1, J = 7 Hz, 2 H), 3.55 (br, 2 H), 1.65 (s, 3 H), 1.40 (s, 3 H), and 1.13 ppm (tr, J = 7 Hz, 3 H) for one isomer, and 7.0-7.6 (m, 5 H), 4.03 (9, J := 7 Hz, 2 H), 3.55 (br, 2 H), 1.60 (s, 3 H), 1.43 (s,3 H), and 1.08 ppm (tr, J = 7 Hz, 3 H) for the other. The signal at 3.55 ppm disappeared when D20 was added. The fraction collected before lm was 4m, obtained in 10% yield, and identified by comparison of the NMR with the known material. The same procedure was used to hydrate 400 mg of Im-3-hfe-d3, yielding 400 mg (92%) of ethyl 2- methyl-3-trideuteriomethyl-3-phenylglycidate (lm-da), which was 72% deuterated from the NMR analysis. Rearrangement of lm. A 576-mg sample of lm was treated with 1.15 ml of FS03H at 0 "C for 3 min, poured into an ice-water-CC14 mixture, and worked up as usual. The crude reaction products were fractionated by preparative TLC using EtOAc in petroleum ether (once with 6% and twice with 4% v/v). Three bands were visible under uv light. Ethyl 3,3-dimethyl-3-phenylpyruvate (2m), an oil (3.7 mg, 0.7%), was isolated from the fastest moving band. Its NMR (CCLJ and mass spectra were superimposable onto those of the FSOsH-catalyzed rearrangement of ethyl 3,3-dimethyl-2-phenylglycerate (10). Ethyl 2-methyl-2-phenylacetoacetate (3m, 418 mg, 78%), an oil, was obtained from the second band. Its NMR (CCL) and mass spectra were superimposable onto those of the major product of the BFs-catalyzed rearrangement of ethyl 2,3-dimethyl-3-phenylglycidate (Im). The third band yielded 59.5 mg (14%) of 2-methyl-3-phenyl-4-hydroxy- 2-butenoic acid lactone (5m): mp 120-122 "C (lit. mp 121-122 OW); A, (cyclohexane) 211 and 260 nm; NMR (CDCl3) 7.45 (s,5 H), 5.04 (9, J = 2 Hz, 2 H), and 2.12 ppm (tr, J = 2 Hz, 3 H). The NMR analysis of the mixture before separation showed 84% of 3m and 16% of 5m, the signal at 1.18 ppm for 2m being barely noticeable. The same treatment was supplied to 300 mg of lm-ds, which yielded 2 mg of 2m-d3,209 mg of 3m-d3 in which the singlet at 1.67 ppm integrated for only 0.67 H, and 15 mg of 5m-d2, having a full methyl at 2.12 ppm. Rearrangement of threo- and erytbro-lm. The above reaction was repeated using 133 mg of either threo- or erythro- lm in 0.26 ml of FS03H. After workup, 107 and 90 mg of an oil were obtained, respectively, each analyzing by NMR for 84% 3m, 16% 5m, and a trace of 2m. Rearrangement of Ethyl 2,3-Dimethyl-3-phenylglycidate (Im). Treatment of 200 mg of Im with 0.43 ml of fluorosulfonic acid for 3 min at 0 OC and workup yielded 140 mg of an orange semisolid product which contained 52% 3m and 48% 5m plus a trace of 2m (NMR analysis). Reaction of lm in Dilute Fluorosulfonic Acid. Qualitative tests were performed using 200 mg of lm in (a) 0.4 ml of acid and 0.05 ml of water, (b) 0.3 ml of acid and 0.05 ml of water, and (c) 0.3 ml of acid and 0.1 ml of water. The major products were 3m (along with some 4m and 5m), 4m (along with some 3m), and 4m, respectively. In the last two experiments some starting material remained. Ethyl 2-Ethyl-3-methyL3-phenylglycerate (le). A solution of 482 mg (2.06 mmol) of E-Ie in 2 ml of tetrahydrofuran was added to 25 ml of perchloric acid in 50% aqueous tetrahydrofuran (30% by weight). The reaction mixture was heated in an oil bath at 45 OC for 1 h, diluted with 150 ml of water, and extracted with two 50-ml portions of ether. The combined ether extracts were washed with two 50-ml portions of 5% aqueous sodium bicarbonate, dried, and concentrated. Purification of the product mixture by preparative TLC, using 7.5% ethyl acetate in petroleum ether, yielded 385 mg (74%) of le, a thick oil, as a 1:l mixture of threo and erythro isomers: NMR (CC14) 7.0-7.6 (m, 10 H), 4.02 (q, J = 7 Hz, 2 H) and 4.13 (9, J = 7 Hz, 2 H), 3.33 (br s, exchanged with DzO, 4 H), 1.5-2.1 (m, 4 H), 1.58 (s, 3 H) and 1.5 (s, 3 H), 1.18 (tr, J = 7 Hz, 3 H), and 0.5-0.85 ppm (m, 6 H). Ethyl 2-ethyl-3-phenyl-2-hydroxy-3-butenoate (4e, 43 mg, 9%) was also obtained from the first band and was identified by NMR (CCL): 7.20(~,5H),5.45(d,J= lHz,lH),5.14(d,J=1Hz,1H),4.12(q, J = 7 Hz, 2 H), 3.28 (s, 1 H, exchanged with DzO), 1.90 (9, J = 7 Hz, 2 H), 1.12 (tr, J = 7 Hz, 3 H), and 0.90 ppm (tr, J = 7 Hz, 3 H). Rearrangement of Ethyl 2-Ethyl-3-methyl-3-phenylglycerate (le). This compound (385 mg, 1.53 mmol) was treated with 0.73 ml of FS03H at 0 OC for 3 min and worked up as described above. NMR analysis of the mixture showed 75% 3e, 9% 2e, and 16% 5e. These components were separated by preparative TLC developing the plates four times with 5% ethyl acetate in petroleum ether. Three bands were seen under uv light. The bands were scraped off and extracted with 10% ethyl acetate in chloroform. The lactone 5e was obtained in 14% yield (40 mg) from the slowest moving band as prisms, mp 79 OC when recrystallized from CC14- petroleum ether: NMR (Cc4) 7.50 (s,5 H), 5.02 (2 H, tr, J = 1 Hz), 2.22-2.75 (d, q, J = 1 and 7 Hz, 2 H), and 1.21 ppm (tr, J = 7 Hz, 3 H); mass spectrum mle 188 (M+), 187,159,143,129,128,115 (base peak), 91, 77, and 29. The second band yielded 203 mg (58%) of 3e identified by com- parison of the NMR and mass spectra with those of the known comp0und.l

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