《有机化学》课程教学资源（文献资料）The Thermal, Aliphatic Claisen Rearrangement.pdf_P6-P10

1428 Chemical Reviews, 1988, Vol. 88, No. 8 oxy-Claisen rearrangement)46 or [2,3] Wittig rearrangement.54 Thomas55 has observed that ketone 67, upon exposure to t-BuOKlt-BuOH, undergoes a [2,3] Wittig rearrangement to "mainly" keto1 68. In contrast, K~reeda~~* has reported that the enolate of phenyl ketone 69 (from MH and MeOH) in toluene not only shows rate enhancement (M = K, -23 "C, tllz = 3.3 h; M = Na, 0 "C, tljz = 2.6 h; M = Li, 96.5 "C, tljz = 1.1 h) but also gives a ratio of Claisen to Wittig product (70:71) of >98:<2 (M = K, Na) and a ratio of -80:20 when M = Li. To ensure exclusive formation of the Claisen product, enolates need only be 0-silylated (65a - 65b) and rearranged to aldehydes (64b). Accordingly, the 0-trimethylsilyl enol ether of ketone 69 affords the 0-trimethylsilyl derivative of ketone 70 upon heating (71 "C, tljz = 0.5 h). Earlier, Sa10mon~~ had demonstrated the utility of the transformation 65b - 64b by preparing the 0-trimethylsilyl enol ethers with (TMS)C1/Et3N. The a-silyloxy aldehydes could be cleaved readily with methanolic periodic acid to afford P,y-unsaturated ketones. 2 i e g I e r 64 65 66 a, X=M, R=alkyl c, X=M. R=O-alkyl e, X=TMS, R=NR,' f. X=TMS, R=O-alkyl b, X=TMS. R=alkyl d, X=M, R=OM OH I 67 6e 69 'C 1 Surprisingly, the ester enolates of generic structure 65c do not undergo a [2,3] Wittig rearrangements7 while their carboxylate-derived dianions (65d) and dialkylamide anions (65e) do rearrange by this pathway.58 Exclusive Claisen rearrangement of these substances can be accomplished via the trimethylsilyl ketene acetals (65f - 64f). This procedure has been described independently by Nakai57 and Ra~cher~~ in thetransformation of ester 72a to its (2)-0-silyl ketene acetal 73 followed by Claisen rearrangement to the masked a-keto aldehyde 74. Significantly, when the C-silylated ester 72b is treated with tetra-n-butylammonium fluoride, formation of the [2,3] Wittig product occurs. On the other hand, the 0-silyl derivative 73 gives the starting ester 72a. This observation has led Nakai to suggest that a common "naked" anion is not involved in the two pathways but that separate C- and O-hypervalent silicon species are responsible for the dual reaction pathways. 2. Divinylcarbinol Derivatives The competitive rearrangement of 4-vinylallyl vinyl ethers has provided information on the relative rates 1) LDA e 'yC0zMe 2) TMSCl or TBSCl R 72a, R=H b, R=TMS 73 74 of substituted allyl residues. Scheme I illustrates such a study60 wherein the P-substitution pattern of the allylic residue of allyl vinyl ether 75 is systematically altered. The vinyl residue reacts twice as fast as the (E)-P-vinyl group (76a:77a) and 19 times faster than the (Z)+vinyl(76b:77b). At first hand, these data suggest that, in a competition between the (E)- and (Z)-p-vinyl groups, the E isomer should react 9.5 times faster (76b:77b to 76a:77a); the observed result is -3:l (76~77~). As has been suggested,61 each nonreacting group is a substitution for its reacting partner and need not offer additive substituent effects in each rearrangement. The presence of a 6-methyl substitution (E configuration) has a limited effect on the rate of rearrangement of vinyl ethers or silyl ketene acetals (cf., 29 vs 30a). Terminal 6,6-substitution with two methyl substituents completely favors formation of 76d over 77d. Parker and Farmar62 have uncovered a subtle selectivity in the rearrangement of the series of divinylcarbinol derivatives 79. The methyl substituent in 79a and 79b provides a small steric decelerationm while the less sterically demanding methoxyl group manifests itself as a decelerating C5-donor group in both 79c and 79d. These observations lend additional support to the Burrows-Carpenter model for C5-donors.31 For divinylcarbinols wherein one of the vinyl substituents is contained in a ring, rearrangement with the acyclic vinyl group is preferred when the acyclic unit is unsubstitued. Thus, vinyl ethers 82a and 82b give 81a and 81b, respectively, with high selectivity. The presence of an (E)-P-methylvinyl group retards acyclic rearrangement, but it still remains the major pathway for the rearrangement of 82d.64965 SCHEME I 75 75 76 77 76'77 a R1=R2=R3=H &Me 2. ' b Rl=R2=Rd=H. R,=Me 95'5 d R.=R,=H. R,=R.,=Me '00 0 c R,=R,=H R,=Rj=Me 78 22

Thermal, Aliphatic Claisen Rearrangement Chemical Reviews, 1988, Vol. 88, No. 8 1429 78 84a, R,=OH. Rz=H b, Rl=H, R,=OH 80 78180 a, R=Me, X=OEt 65135 b, &Me, X=NMez 74126 c, R=OMe, X=OEi 9515 d, R=OMe, X=NMe, 9713 0- 82 a, R=H, n=l b, R=H, n=2 c, R=Me, n=l d, R=Me, n=2 R 81 - 81/83 (CHZ)" dyH 0 8911 1 8811 2 50150 65/35 83 3. Elimination Alternative sigmatropic rearrangements are not the only irreversible processes that can compete with the Claisen rearrangement; elimination reactions are troublesome. This undesirable, competitive process is particularly acute when at least one olefin is contained in a ring. Cyclohex-2-en-1-01s have been particularly notorious in this regard. Ireland and co-workers@ have prepared the isomeric allylic alcohols 84a and 84b by reduction of the corresponding enone. The minor axial alcohol 84a, when subjected to mercuric ion catalyzed exchange with ethyl vinyl ether, undergoes elimination to dienic products. On the other hand, the major, equatorial allylic alcohol rearranges to aldehyde 85 without incident. An unfavorable transition state for the Claisen rearrangement in the former case may be the result of steric interactions between the angular methyl group and the forming C-C bond. When confronted with the problem of elimination, the use of an alternative strategy is often beneficial. Thus, allylic alcohol 86, when subjected to the Eschenmoser ketene 0,N-acetal variant, provides only a 45% yield of the desired amide 87a along with the products of disproportionation of the dihydropyridine, the immediate product of elimination. However, the Johnson orthoester route gives the ester 87b in 74% ~ield.~'?~~ D. Stereochemistry 1. Transition State The Claisen rearrangement is a suprafacial, con- *:Hz?oH 86 85 phcH*PR 87a, R=CONMe2 b, R=COzEi certed, nonsynchronous pericyclic process that may be considered phenomenolologically as an intramolecular SN2' alkylation. When the sp2-hybridized C1- and C6-positions of allyl vinyl ether are substituted to provide enantiotopic faces at both termini, the rearrangement can proceed through two pairs of stochastically achiral transition states to provide two racemic diastereomers bearing newly created centers of asymmetry at C2 and C3 of the products (Scheme 11). Thus, achiral allyl vinyl ether 91 can provide two enantiomeric chairlike transition states 88 and 90, both of which lead to the racemic diastereomer 89. Similarly, the enantiomeric boatlike transition states 92 and 94 provide racemic, diastereomeric aldehyde 93. The two transition states are inherently unequal in energy and the ratio 89:93 reflects the transition-state geometry. In a detailed study modeled after the Doering and Roth experiments that revealed the preferred chairlike transition state for the Cope rearrangement,69 Schmid26bic and his collaborators have examined the rate and stereochemistry of rearrangement of the four crotyl propenyl ethers 91a-d in the gas phase at 160 "C. All isomers show the expected negative entropy of activation (AS* = -10 to -15 eu) with enthalpies of activation ranging from 25 to 27 kcal/mol. Each isomer shows a clear preference for the chairlike transition state (91a, 95.9:4.1; 91b, 94.7:5.3; 91c, 95.54.5; 91d, 95.4:4.6). The E isomer 91a is found to rearrange an order of magnitude faster than the Z,Z isomer 91b, with the other two geometric isomers intermediate in rate. The E,E and Z,Z isomers rearrange through a chairlike transition state to give the threo isomer 89a (89b) as the major product; likewise, the Z,E and E,Z isomers give the erythro isomer 89c (89d) as the predominant stereoisomer. Since the four isomers 91 all proceed through the chairlike transition state, a change in the geometry of a single double bond exchanges the enantiotopicity of the faces of the double bond and leads to the opposite stereoisomer. Indeed, any pairwise change in olefin geometry for a given transition state, or single change of olefin geometry and change in transition state, results in the formation of the same dia~tereomer.'~ 2. Vinyl Double-Bond Geometry Before proceeding to other substituent effects and how they control the transition state of the Claisen rearrangement, it is appropriate to consider the methods that are available to control the geometry of the vinyl double bond. Unfortunately, no convenient

1430 Chemical Reviews, 1988, Vol. 88, No. 8 SCHEME I1 Ziegler Chair A r L Chair B methods are available for the selective preparation of propenyl ethers. The same difficulty exists with the Johnson orthoester method. The use of orthoesters derived from propionic acid derivatives and their higher analogues fail to give stereochemically defined ketene acetals.71 However, the ketene 0,N-acetal rearrangement does provide for selectivity. Sucrow and Richter72 have examined the Claisen rearrangement of the dimethyl acetal of N8-dimethylpropionaide with (E)- and (2)-crotyl alcohol (Scheme 111). Although the intermediate ketene 0,N-acetals are generated in situ and are not isolated, the assumption that a chairlike transition state is operable, coupled with a preferred axial orientation of the C1-methyl group of the (E)- ketene O,N-acetal(95, loo), correctly accounts for the stereochemistry of the products. The latter supposition is tenable as the dimethylamino group assists in delocalizing charge in the transition state and interacts with the C1 substituent when it is equatorially disposed.73 An alternative approach to the use of the ketene 08-acetals has been offered by the work of Fi~ini~~ who has employed 1-(N8-diethylamino)-l-propyne (101) as the propionate source; however, no stereochemical study was conducted. Recognizing that the (2)-ketene 0,Nacetals of Scheme I11 are the products of thermodynamic control, Bartlett and Hal~ne~~ have prepared the less stable, kinetic @)-ketene 0,N-acetal by the stepwise, cis addition of the crotyl alcohols across the triple bond of the Ficini ynamine (Scheme IV). The slow addition of the crotyl alcohol to the ynamine at 140 OC serves to make rearrangement, a trap for the kinetic addition product, competitive with isomerization. Protonation of the ynamine provides the ketene immonium cation 102, which adds alkoxide preferentially syn to the hydrogen atom via path A. In the case of the (2)-alcohol, a 2.51 ratio of 108 to 107 is obtained; the (E)-alcohol also preferentially follows path A through 105 leading to a 2:l ratio of 107 to 108. The Ireland variant21 of the Claisen rearrangement has proved the most adaptable for the control of vinyl 92 93 (racemic) 94 SCHEME I11 96 (E, equatorial) 95 (E, axial) NMe2 95% I CONMe, 97 (erythro) CONMe, Me 98 (threo) 13% I I 99 (Z, equatorial) 100 (Z, axial) olefii geometry. The deprotonation of esters by lithium dialkylamide bases developed by Rathke22-76 has proved amenable to the generation of specific enolates. Thus, treatment of butenyl propionates 110 and 114 (Scheme V) with lithium diisopropylamide (LDA) in THF under these kinetic conditions forms principally the (2)-lithium enolates, which upon silylation (tert-butyldimethylsilyl (TBS) gives the (E)-0-silyl ketene Rearrangement of silyl ketene acetal 109 provides an 87:13 mixture of acids 111 and 115 after desilylation while 116 gives an 89:ll ratio of 115 and 111. These two products can also be obtained by using 23% HMPA-THF (HMPA = hexamethylphosphoramide)

Thermal, Aliphatic Claisen Rearrangement Chemical Reviews, 1988, Vol. 88, No. 8 1431 TABLE I. Geometry of Enolate Formation OR2 R ox H OX H OR2 RICH~CO~R~ - 117 118 llQ entry 1 2 3 4 5 6 7 8 9 10 11 ester 117a 117b 117c 117d 117e 117a 117b 117c 117c 117f 117d X" TBS TBS TMS TBS TES TBS TBS TMS TES TES TBS solventb THF THF THF THF 23% HMPA-THF 23% HMPA-THF 23% HMPA-THF 23% HMPA-THF 23% HMPA-THF 23% HMPA-THF 23% HMPA-THF "TBS = tert-butyldimethylsilyl; TMS = trimethylsilyl; TES = triethylsilyl. *Enolates were generated with LDA, -70 to -78 "C. SCHEME IV rr NE!, NE!, I I 105 106 103 104 107 (threo) YCONEt, Me 108 (erythro) as an optimal solvent system for the generation of the therm~dynamic'~ (E)-lithium enolates ((2)-0-silyl ketene acetals 112 and 113). 2-(0)-Silyl ketene acetal 112 provides an 81:19 mixture of 115 and 111 while 113 affords an 86:14 mixture of 111 and 115. The major diastereomer in each rearrangement arises through the chairlike transition state, and once again, a single exchange of olefin geometry results in the other diastereomer becoming the major product. The erosion of diastereoselectivity can be attributed to two factors: the geometric integrity of the silyl ketene acetals and the selectivity of the chairlike vs boatlike transition state. Table I provides examples for the selectivity of enolate formation by the LDA/silylation procedure.82 The entries are listed in ascending bulk of the alcohol porSCHEME V 111 112 OSIR, 0 11 0 23% HMPA-THF 23% HMPA-THF I 116 OSIR, tion of the ester group for a given solvent. In general, enolate formation by the kinetic deprotonation procedure is somewhat more selective than the thermodynamic conditions. Because the silyl ketene acetal ratios are approximately equal to, or better than, the ratio of diastereomers 11 1 to 115, the chairlike transition state is virtually the exclusive pathway for rearrangement. 3. Secondary Allylic Alcohols Although the aliphatic Claisen rearrangement of secondary allylic alcohols had been recognized to provide E double bonds,83 Faulkner and Petersen@ have examined the selectivity of olefin formation as a function of C2 substituents. The vinyl ether rearrangement of vinyl ether 120a provides a 9O:lO ratio of (E)- to (2)-unsaturated aldehydes 121a. The congener 120b bearing an isopropyl rather than an ethyl substituent is more selective affording a 93:7 ratio of (E)- to (2)- olefinic aldehydes 121b. An increase in the steric bulk of the C2 substituent produces higher stereoselectivity. Thus, ketene 0,N-acetal rearrangement of 120c gives an E:Z ratio of 99.4:0.6 while the product from the 2- methoxypropene derivative of 2-methylpent-1-en-3-01 (120d) provides less than 1% of the (Z)-olefin. Simi-

1432 Chemical Reviews, 1988, Vol. 88, No. 8 Ziegler larly, Katzenellenbogena5 has reported less than 1 % of (Z)-olefin in the silyl ketene acetal rearrangement of 120e and Johnsona6 has observed >98% E selectivity in the orthoester rearrangement of 120f. This dramatic increase in selectivity observed in the C2,C4-substituted examples has been rationalized as the result of a pseudo-1,3-diaxial interaction in chairlike transition state 123 that leads to the (2)-olefin as opposed to the less congested chairlike transition state 122 that gives the (E)-~lefin.~~~~~~~~ Yo + + tR Z Z 120 a, %El, Z=H 121 b, R=i-Pr, Z=H c, R=Et. Z=NMe, d. R=Et, Z=Me e, R=n-C,H,3, Z=OTBS 1, R=CH,CH,CH(Me)=CH, /- . /f *\<<,.,i,\ n .*-.-7 .-’ R %. .-, &,.*. L*-o . /fl 122 123 When the secondary allylic alcohol has a substituent at the terminus of the double bond (i.e., C6), a center of asymmetry is destroyed during the rearrangement as a new one is created. This process has been often called “self-immolative” a9 and involves the “transfer of chirality”.2f In the sense that racemic substances bearing centers of asymmetry are chiral, and recognizing the concerted, suprafacial nature of the rearrangement, the transformation of Scheme VI is, by necessity, chiral throughout. In more modern terms, that which is transferred is stereogenicityw (Le., stereochemical information), and when practiced with enantiomerically pure allyl vinyl ethers (124), the rearrangement affords enantiomerically pure products (126). In the example of Scheme VI, the R,E enantiomer 124 bearing an equatorial R1 substituent undergoes bond formation on the si face of the allylic double bond to produce the R,E enantiomer 126. Conformational inversion of 124 leads to (R,E)-127. This conformation can undergo re bond formation through transition state 128 having the R1 substituent axial, resulting in the formation of S,Z enantiomer 120. Thus, the transition-state integrity may be monitored with enantiomerically pure reactants by measuring the enantiomeric excess of the dihydro aldehydes from reduction of 126 and 129. In the racemic series, the value (E - Z)/(E + 2) equals the enantiomeric excess that would be obtained using enantiomerically pure allylic alcohols. The chairlike vs boatlike transition state is not detectable in this case because there is no C1 substituent. Hill has observed the “transfer of chirality” in the vinyl ether rearrangement of enantiomerically pure cyclopent-2-en-l-ol.g1a The Eschenmoser and Johnson variants with enantiomerically pure (E)-pent-3-en-2-01 give products with 90% retention of enantiomeric purity as determined by optical rotati~n.~~~~~~~~ An ingenious, enantioconvergent variation on this theme has been executed by Chan.93a The enantiomers of propargyl alcohol 130 are prepared by resolution. The R enantiomer is reduced to the (R,Z)-allylic alcohol 131 while the S enantiomer is converted to the (S,- E)-allylic alcohol 132. Rearrangement to form the aldehyde, ester, or amide 133 occurs with “chirality transmission” of 94-99%. Thus, the (R,Z)-olefin exposes the re face while the (S,E)-olefin invokes the same re face, affording a single enantiomer, the (S,E)-olefin 133. Clearly, the other enantiomer, (R,E)-133, is accessible by exchanging the reduction procedure for each enantiomer of 130.94 The advent of the Sharpless kinetic resolution procedureg5 and the Midland asymmetric reduction of a,@-acetylenic ketones% has made a variety of secondary allylic alcohols readily available in both enantiomeric forms, thereby obviating the use of classical resolution. SCHEME VI (R, and R, lowest carbon priority) LR L J 125 126 124 127 128 129