《有机化学》课程教学资源（文献资料）The Thermal, Aliphatic Claisen Rearrangement.pdf

Chemical Reviews Volume 88. Number 8 December 1988 The Thermal, Aliphatic Claisen Rearrangement FREDERICK E. ZIEGLER steriing Ctmm!.qtry Labaatory. Yale UnivennV, New Haven. Connecticur 08511-8118 Receh.ed April 25. 1988 (Revised Manusnipt Received Seplember 8. 1988) Contents I. Introduction 11. Historical Overview 111. Mechanistic Aspects A. Kinetics B. Retro-Clalsen Rearrangement C. Competitive Rearrangements 1. [3.3] Claisen vs [2,3] Wmig 2. Diinylcarbinol Derivatives 3. Elimination D. Stereochemistry 1. Transition State 2. Vinyl Double-Bond Geometry 3. Secondary Allylic Alcohols 4. Tertiary Allylic Alcohols 5. RingBearing Substrates Rearrangement IV. Heteroatom Substituents A. The Vinyl Group 1. C, Hetero Substituents 2. C, Carbon Hetero Substituents 1. Oxygen Substituents 2. Silicon Substituents B. The Allylic Group V. Remote Asymmetry A. Acyclic Substrates B. Ring-Bearing Substrates VI. Consecutive Rearrangements A. Sequential Rearrangements 8. Tandem Rearrangements C. Iterative Rearrangements A. (1,llRearrangements 8. (1.2JRearrangements C. (1.41-Rearrangements D. (1.5lRearrangements E. (1.61-Rearrangements F. (2.41-Rearrangements G. (4.5l-Rearrangements H. (4.61-Rearrangements I. (5.61-Rearrangements VII. Synthetic Applications VIII. Biochemical Aspects IX. Concluding Remarks 1423 1424 1425 1425 1427 1427 1427 1428 1429 1429 1429 1429 1431 1433 1433 1435 1435 1435 1435 1436 1436 1437 1438 1438 1438 1440 1440 1440 1441 1442 1442 1442 1443 1444 1444 1444 1445 1446 1446 1448 1448 A. Frederick E. Ziegier received his B.S. from Fairiegh Dickinson University in 1960 and Ph.D. in 1964 from Columbia University where he studied under Gilbert Stork. As an NSF postdoctoral student. he spent 1 year in the laboratory of George Buchi at The Massachusetts Institute of Technology. He joined the Yale University facuHy in 1965 where he currently hokk the rank of Professor of Chemistry. His research interests include the synthesis of physiologically active natural products, the study of the stereochemistry of aganic reactions. and the development of new synthetic methods. I. Introduction This past year the diamond annivenary of the publication of Ludwig Claisen’s paper “Uber Umlagerung von Phenol-allyl-athern in C-allyl-phenole^ describing his now eponymous rearrangement’ was observed. And what a gem it has proved to he! Ironically, the majority of the text of the paper and all the experimental details dealt with the substance of the title while the first paragraph mentioned, in almost parenthetical fashion, the rearrangement of the 0-allylation product of acetoacetic ester 1 to its C-allylated isomer 2 upon distillation in the presence of ammonium chloride. Arguably, the aliphatic rearrangement has stimulated more interest in both its mechanistic and synthetic aspects than its aromatic counterpart. Today, the aliphatic Claisen rearrangement is but one member of the class of [3,3] sigmatropic rearrangements. The prototype for the rearrangement is the transformation of allyl vinyl ether 3 into 4-pentenal (4). 0009-2665/88/078&1423$06.50/0 0 1988 American Chemical Society

1424 Chemical Reviews, 1988, Vol. 88, No. 8 Ziegler dehydrohalogenation to form the archetypical allyl vinyl ether (3), which underwent successful rearrangement to aldehyde 4 at 255 “C. In addition, allyl isopropenyl ether (9) was prepared by acid-catalyzed elimination and was subjected to rearrangement to afford ketone 10. H‘ xo4 0- 8 - 2550c L 1 2 This review will deal with the history, mechanism, stereochemistry, and applications of the thermal, aliphatic rearrangement2 over the past 75 years, as recent publications have provided excellent summaries of the effect of catalysts on the rea~angement.~ While the contributions to this area are legion, an effort will be made to deal with both historical contributions and those reports that exemplify the scope of the reaction. Although heteroatom Claisen rearrangements will not be covered, examples will be provided as they apply to the discussions at hand. I I. Hlstorlcal Overvlew Bergmann and Corte (1935)4 and Lauer and Kilburn ( 1937)5 investigated the rearrangement of ethyl 0-cinnamyloxycrotonate (5) in the presence of ammonium chloride to determine if “transposition” of the allyl unit occurs, as had been established in the aromatic series? The former collaborators reported the formation of the “nontransposed” product 6 and “transposed” 7 while the latter investigators observed only the product of “transposition”. The formation of P-keto ester 7 provided access to a product formally derived from the s$’ C-alkylation of cinnamyl halides with acetoacetic ester anion. PhT 5 P.31 oTph C0,Et 7 Bergmann and Corte employed Claisen’s method7 of ammonium chloride catalyzed exchange of cinnamyl alcohol with ethyl 3-ethoxy-2-crotonate for the formation of 5 while Lauer and Kilburn used sodium cinnamylate and ethyl P-chlorocrotonate. The use of ammonium chloride in the rearrangement step soon disappeared, although it had been shown to have “a small, but significant, increase in rate” as a heterogeneous catalyst.8 While the @-keto esters provided access to y,b-unsaturated acids by Haller-Bauer cleavage (Le., retroClaisen condensation) and y,d-unsaturated ketones by acid hydrolysis, formation of y,d-unsaturated aldehydes had not been realized. In 1938, Hurd and Pollackga subjected @-bromoethyl allyl ether to base-promoted 9 10 In the early 1940s, Carrolllo investigated the basecatalyzed reaction of acetoacetic ester with allylic alcohols to produce olefinic ketones.ll In particular, the stereospecificity of the reaction was demonstrated in the case of the structural isomers cinnamyl alcohol (1 1) and phenylvinylcarbinol (13), each giving a transposed product. Aware of the results of Bergmann and Lauer, Carroll proposed a mechanism that invoked sN2’ displacement of hydroxide by acetoacetate anion. Kimel and Cope12 (1943) clarified the mechanism by demonstrating that acetoacetic acid esters derived from allylic alcohols undergo the rearrangement. Moreover, the use of diketene provided a reactive equivalent of acetoacetate that made the formation of substrates routine. Thus, this variation of the reaction provided nonacidic conditions, compared to those of Hurd, for the generation of y,d-butenyl methyl ketones. )!.& + EtOH + CO, CH3COCH2C02EWNaOE1 Ph *OH 12 or diketene; NaOEt 11 LPh + EtOH + CO, CH3COCH,C02EWNaOEt Ph or diketene; NaOEt 13 14 The generation of vinyl ethers by the dehydrohalogenation procedure of Hurd did not provide a general route for the derivatization of allylic alcohols. A solution to this problem was provided by Burgstahler and Nordin13 who adapted the mercuric acetate catalyzed exchange of alcohols with alkyl vinyl ethers14 to the formation of allyl vinyl ethers (15 - 16).15 These investigators were able to demonstrate that the rearrangement was successful in systems wherein at least one of the double bonds is contained in a ring (16 - 17). ROCH=CH, - Hg(OAc)z P A q? CHO 15 16 17 In 1967, Marbet and Saucy reported16 the acid-catalyzed exchange and rearrangement of seemingly labile tertiary allylic alcohols with 2,2-dimethoxypropane or 2-methoxypropene that resulted in the formation of methyl ketones.17 The conversion of linalool to gera-

Thermal, Aliphatic Claisen Rearrangement nylacetone laid the groundwork for a commercial synthesis of vitamin A alcohol. The first practical example of the preparation of y,b-unsaturated carboxylic acids via the aliphatic Claisen rearrangement was demonstrated by Arnold and co-workers18 in 1949.19 The allylic esters 18 and 20 of diphenylacetic acid underwent stereospecific rearrangement upon treatment with mesitylmagnesium bromide at ambient temperature. diradical Chemical Reviews, 1988, Vol. 88, No. 8 1425 Ph 20 21 Other variations employed sodium hydride as the base in refluxing toluene;18a9z0 however, a significant breakthrough was reported by Irelandz1 who, following Rathke's reportzz of the use of lithium dialkylamide bases for the generation of ester enolates, demonstrated that the method served as a means to achieve the Claisen rearrangement of acylated allylic alcohols at ambient temperature (22 - 23) and, as will be seen later, provided a method for the control of enolate geometry. Both the enolates and their 0-silyl ketene acetals underwent facile rearrangement.z3 Y l)L'cA'THF 2) TMSCI e 0 7 H30+ * 7 0 0 22 23 24 "'rf OTMS Although Ireland's contribution improved the formation of y,b-unsaturated acids, it was preceded by two independent contributions that realized amides and esters via the Claisen rearrangement. In 1964 Eschenm~ser~~~p~ adapted Meerwein's observationsz4c on the exchange of amide acetals with allylic alcohols, thereby facilitating the formation of y,b-unsaturated amides upon rearrangement (25 - 26). In a similar fashion, 1970 witnessed Johnson's reportz5 of the acid-catalyzed exchange of ethyl orthoacetate with allylic alcohols and the subsequent formation of y,b-unsaturated esters upon rearrangement (27 - 28). 0 II MezNC C02Me * MeC(OMe)?NMeZ, xylene 1 4OoC, 14h ''O I Me' OH 25 26 MeC(OEt), propionic acid m + OH OH 138'C, 3h 27 C02Et Et02C 28 0% - 100% diyl 0 Figure 1. Transition-state profile of the aliphatic Claisen rearrangement. ZZZ. Mechanistic Aspects A. Kinetics The ability of the Claisen rearrangement to give transposed structures led Hurd and Pollackgb to suggest a cyclic mechanism. The rearrangement of allyl vinyl ethers displays a negative entropyz6 and volumez7 of activation, both of which support a constrained transition state relative to ground-state geometries. Firstorder kinetics8Vz6 and the lack of crossover products8 argue for the intramolecularity of the reaction. The overall exothermicityz6 of the rearrangement of allyl vinyl ethers indicates an early transition ~tate.~J~ Using secondary deuterium isotope effects as a mechanistic probe, Gajewskiz9 has concluded that bondbreaking is more advanced than bond-making in the rearrangement of allyl vinyl ether itself. Thus, the transition state (TS) has been suggested to resemble more closely the diradical than the 1,4-diyl. Figure 1 (More O'Ferrall-Jencks diagram) locates the transition state for allyl vinyl ether above diagonal A (diradical > diyl) and below diagonal B (early, not late, TS). Dewar, using MIND0/3 calculations, has supported an early transition state for allyl vinyl ether with bondmaking being more advanced than bond-breaking, thereby requiring diyl character in the transition state.3o Substituents play an important role in affecting the rate of the Claisen rearrangement. Burrows and Car- enter,^^ using phenyl anion as a transition-state model, have predicted that ?r-donor substituents at C1, Cz, and C4 of allyl vinyl ether should increase the rate of the rearrangement, while substitution at C5 and c6 should cause deceleration. However, Dewar30 has argued that a C5-methoxy substituent should have a greater accelerating effect than a C,-methoxy group. The presence of electron-donating groups, e.g., EtO-, R3SiO-, and Me2N-, at Cz of the allyl vinyl ether causes a dramatic rate acceleration. Thus, the 2-(trimethylsily1)oxy (29; tllz = 210 f 30 min at 32 0C)21 and the 2-(tert-butyldimethylsilyl)oxy (31a; tljz = 107 min at 35 0C)3z derivatives rearrange with facility under near ambient conditions, while allyl vinyl ether (tllz = 1.7 X lo4 min at 80 0C)33 requires higher temperatures for rapid rearrangement. While both 29 and its 6-methyl congener 30a (tl,z = 150 f 30 min at 32 oC)zl rearrange

1426 Chemical Reviews, 1988, Vol. 88, No. 8 Ziegler kinetic parameters. Rate accelerations are observed for the C2-CN (krel = ill), C3-CN (krel = 270), and C4-CN (krel = 15.6) compounds while decelerations occur for the C1-CN (krel = 0.90) and C5-CN (krel = 0.11) isomers relative to allyl vinyl ether. The formation of anionic species increases the rate of the rearrangement. The enolates of allyl esters should be considered as the prototypes of strong C2 ?r-donors as they rearrange at ambient temperatures.21 Denmark has reportedm the first example of a carbanion-accelerated Claisen rearrangemen~~l The use of hexamethylphosphoramide (HMPA), as opposed to l&crown-G/THF, accomplishes the conversion of 38a - 39a at a lower temperature (50 "C) and in a higher yield (78%). This solvent-induced rate enhancement has been interpreted as ion-pair dissociation. Disubstitution at C1 (38b - 39b) causes a greater rate enhancement (20 "C, 15 min),42 similar to the silyl ketene acetal case. Phsoq] HMPA * / R R 38 PhSO, at nearly the same rate, the C4-alkyl-substituted isomer 3 1 b rearranges an order of magnitude more rapidly than This difference suggests a kinetic stabilization of the bond-breaking process by the alkyl group in 31b. R- I OY GTMS GTMS OTBS 29 30a, R,=R,=H 31a. R=H b, R,=Me, R,=H b, R=C,Hll c, R,=R,=Me OMe O4 O4 32 33 O4 34 Coates and C~rran~~ have measured the rates of rearrangement of the C4-, C5-, and C6-methoxy-substituted allyl vinyl ethers at 80 "C in benzene. The 4- methoxy derivative 32 rearranges 100 times faster than the parent while the 6-methoxy isomer 34 is 10 times faster, thereby demonstrating a strong kinetic stabilization in the former case and a vinylogous, kinetic anomeric effect in the latter.35 The observation of this effect is contrary to the Burrows-Carpenter model. In addition, the 5-methoxy isomer 33 is found to rearrange 40 times slower than the parent, in disagreement with the Dewar prediction. Coates and Curran have suggested a transition state for these systems with dipolar character (enolate-oxonium ion pair). When the solvent is changed from benzene to methanol, 32 and 34 show a 20- and 70-fold rate increase, respectively. In general, solvents have little effect on the rate of the rearrangement. Gaje~ski~~ has attributed the rate enhancement and the greater degree of bond-breaking in the transition state of the Ireland-Claisen rearrangement to the greater stability of the 2-[ (trimethylsilyl)oxy]-1-oxaallyl moiety over its oxaallyl counterpart (Figure 1). This conclusion derives from an examination of the heats of formation of the oxaallyl radicals and supports21b the finding that the relative rates of rearrangement of silyl ketene acetals 30 are 30c > 30b > 30a.37 The effect of the (trimethylsily1)oxy group is not general to all [3,3] sigmatropic rearrangements as 2-[ (trimethylsily1)- oxy]-3-methyl-1,5-hexadiene undergoes a Cope rearrangement with a half-life of 2 h at 210 "C. Although the Johnson and the Eschenmoser variants are conducted at elevated temperature, these conditions are required for the alcohol exchange reaction, not necessarily for the rearrangement. This point is amply demonstrated in the latter instance when ketene OJVacetals are generated by an alternative route (35 + 36 - 37).38 0 35 36 37 In an independent study, Carpenter and Burrows39 have synthesized the five isomeric cyano-substituted derivatives of allyl vinyl ether and have measured their 39 a, R=H b, R=Me 40 The Carroll rearrangement is accelerated by carbanion formation. Wilson43 has demonstrated that /3-keto ester 41, formed by 4-(dimethylamino)pyridine (DMAP) catalyzed addition of (E)-2-buten-l-ol to diketene,44 provides the @-keto acid 43 when treated with 2 equiv of lithium diisopropylamide (LDA) at -78 "C in THF followed by heating to reflux. Decarboxylation is readily accomplished in refluxing carbon tetrachloride to give the ketone in 95% yield. When 1 equiv of base is used, no reaction is observed. The thermal reaction in the absence of base requires heating at 200 "C, and the ketone is isolated in only 37% yield. In a similar fashion, BUCK& has observed acceleration in the rearrangement of 3-(allyloxy)-2-butenoic acid 44 prepared by alkoxide addition to the 3-chloro-2-butenoate. When the acid is treated with 1 equiv of KH in refluxing toluene for 2-6 h, the potassium carboxylate is stable. However, the use of 2 equiv of KH effects rearrangement via dianion 45 under the same conditions, affording ketone 46 in 68% yield upon acidification and decarboxylation. The rate enhancement occurs for substrates derived from secondary allylic alcohols, but not for primary allylic alcohols. Silyl ketene acetals prepared from secondary alcohols have been observed to rearrange faster than those derived from primary allylic alcohols.21b a-Allyloxy ketones have displayed remarkable rate accelerations. For example, Koreeda and Lueng~~~~ have generated the enolate 48a by conjugate addition of Me,CuLi to 2-(allyloxy)-2-cyclohexenone (47); rearrangement to acyloin 49a is complete in 15 min at 0 oC.46b The rate enhancement has been attributed to an allyl radical/oxyoxaallyl radical anion (semi-dione) pair. For comparison, the silyl enol ether 48b is slower

Thermal, Aliphatic Claisen Rearrangement Chemical Reviews, 1988, Vol. 88, No. 8 1427 ether as its tetracyanoethylene derivative and to the left by formation of the bisulfite adduct of the aldehyde. Decomposition of the bisulfite adduct reestablishes the equilibrium. These equilibria are presumably driven by the strain of the cyclopropane ring.49p50 7 2 equiv. LDATHF * 00 41 -78 'C -> 65 OC F * +CO2H I wo THF 42 43 L- &CO~H 2 equiv. KH 44 r 1 I) toluene, 120 "C 2) H30i L J 45 46 to rearrange, having tl/P = 1.6 h at 62.5 "C. In a related study, P~naras~~ has compared the relative rates of rearrangement of 2-(allyloxy)-3-methyl-2- cyclohexenone and its derivatives. In refluxing THF (65 "C), the parent ketone 50a has tll2 = 340 h, affording the diosphenol51, while the rearrangement of carbomethoxyhydrazone 50b to 52a is appreciably faster (tl = 22 h). The sodium salt of the hydrazone (50c) is the fastest of the three, rearranging to give 52b with t,2 = 1.5 h. This method has proved amenable to forming vicinal quaternary centers, and in the case of the carbomethoxyhydrazones 52, a subsequent Wolff-Kishner reduction can be conducted to remove the accelerating f~nctionality.~~ 47 48a. R=MeCuLi 49a, R=H b, R=TMS b, R=TMS R OH RN %la, R=O 51 52a, R=NN(H)C02Me b, R=NN(H)CO,Me b, R=NN(Na)CO,Me c, R=NN(Na)CO,Me B. Retro-Claisen Rearrangement The Claisen rearrangement, unlike its all carbon analogue the Cope rearrangement, is an irreversible reaction, except for several specially designed substrates. Vinylcyclopropanecarboxaldehyde (53) has been shown to be in rapid equilibrium with dihydrooxepine (54). Similarly, unsaturated aldehyde 55 forms a 7:3 equilibrium mixture with vinyl ether 56. The equilibrium is shifted to the right by trapping the vinyl U'CHO - u- 53 54 g+= 73 40 55 56 Oppolzer51 has observed that silica gel chromatography of aldehyde ester 57a provides recovered substrate (68%) in addition to unsaturated ester 58. During the same period, Boe~kman~~ observed that the rearrangement of 57a to 58 occurs quantitatively at room temperature in 24 h. However, the less strained homologue 59a, upon heating in refluxing toluene in the presence of a catalytic amount of HOAc, provides an equilibrium mixture of 59a and 60 (89:ll). Support for a sigmatropic rearrangement rather than a pathway invoking stepwise formation of carbocation intermediates follows from the observation that the stereoisomer 59b does not undergo rearrangement under conditions that are successful with 59a. However, BF3-Et,0 at room temperature is able to convert stereoisomer 57b into 58, ostensibly through a carbocation intermediate that may only be required for the isomerization (57b - 57a) and not necessarily for the rearrangement. These investigators have also observed acceleration in the BF3.Et20-catalyzed rearrangement at -78 "C in alkyl-substituted congeners of 59a. These observations have led Boeckman to suggest that the minor product, unsaturated ester 62, formed in the BF,.EkO-catalyzed Diels-Alder reaction (-78 "C) between cyclopentadiene 61 and methyl 2-acetylacrylate, may well arise from the major product of the reaction, norbornene 63, by way of the catalyzed retro-Claisen rearrangement.53 57a, R,=CHO, Rz=C02Me b, R1=CO2Me, Rz=CHO C0,Me 58 59a, Rl=CHO, R2=C02Me 60 b, Rl=COzMe, RAHO 61 Br COMe 62 63 C. Competitive Rearrangements 1. [3,3] Claisen vs [2,3] Wiffb Rearrangement Conceptually, a-allyloxy enolates of the type 65a can undergo either [3,3] sigmatropic rearrangement (anionic