Claisen Rearrangement at Elevated Temperatures

Thermally promoted Claisen rearrangement of simple allyloxypyrimidines is difficult to effect. 2-Allyloxypyrimidine largely resists rearrangement even at 200 °C. 4-Allyloxypyrimidines can be rearranged at elevated temperatures <67AHC(8)143> a mixture of the C5- (47) and the N3-allyl derivative (48) was formed from 4-allyloxy-2-phenylpyrimidine on heating in aniline (Equation (6)). 

The metastable byproduct of [4+2] cycloaddition was detected when the reaction of cyclopentadiene with diphenylketene was (Equation (38)) was examined by low-temperature NMR experiment at — 30°C.67 The [4+2] cycloadduct was not observed at elevated temperature because easily isomerizes to [2+2] cycloaddition product via [3,3] sigmatropic (Claisen) rearrangement. This observation was supported by kinetic measurements NMR) and isolation of [4+2] cycloadduct.68 Mechanism proposed by Machiguchi and Yamabe was re-examined by Singleton.69... 

This method was further improved when it was found that readily available allyl esters of the general formula 493 could also be involved in Claisen rearrangements via intermediate formation of ketene derivatives such as lithium enolates 494 or trimethylsilyl ketene acetals 495 (the Ireland-Claisen variant" ). Moreover, rearrangement of these substrates into unsaturated acids 496 occurred easily at room temperature or below. This was in striking contrast to all previous versions of the Claisen rearrangement, which required heating at elevated temperatures (140-160 °C). The Ireland (silyl ketene acetal) variant of... 

When the Claisen-Cope rearrangement is applied to (-)-ci5-carveol (54 Scheme 3) at 100 °C, a dextrorotatory mixture of aldehydes (55) is isolated after the initial Claisen rearrangement, in addition to small amounts of the Claisen-Cope ( )-unsaturated aldehyde (57) ([ajo = -5 ) and its (2)-isomer. Thermolysis of (55) at 150 C gives aldehyde (57) ([a]o = -8.4 ) and at 400 C the product displays no rotation. At elevated temperature the reaction presumably occurs via a diradical species as the rotation of ent- Sl), prepared via (56) from (54), is [a]o = -(-12. ... 

The nucleophilicity of sulfur and its ability to stabilize a-carbanions provide sulfur compounds with unique opportunities for sigmatropic processes consecutive rearrangements are no exception. The formation of salt (140) via Sn2 alkylation of ( )-2-butenyl bromide (139) followed by deprotonation leads to the intermediate allyl vinyl ether (141) which, under the conditions of the deprotonation, undergoes a thio-Claisen rearrangement to afford thioamide (143 Scheme 10). Thermolysis of (143) at elevated temperature affords the Cope product (142) in addition to some of its deconjugated isomer. Several unique characteristics of the thio-Claisen sequence should be noted first, the heteroatom-allyl bond is made in the alkylation step, this connection teing not notrtudly practised in the parent Claisen reaction ... 

SCHEME 7.5 Conducting the Claisen rearrangement of the aryl propargyl ether in diethylanihne at elevated temperatures. Formation of the desired chroman product is accompanied by generation of furan by-product in successively increasing amounts. 

Scheme 7.23 illustrates the diastereoselectivities observed under various conditions in the synthesis of 2,3-dimethyl pent-5-enamides from ( )-2-buten-l-ol [11, 14, 25, 26, 47]. The anti isomer usually predominates with the exception of the thermal Ficini-Claisen variant (Scheme 7.23, Eq. 2) [18]. In this case, slow addition of the allylic alcohol to the ynamine at elevated temperatures resulted in a 1 2 mixture of aniv.syn products. This result can be explained by assuming that addition of the alcohol to the ketene iminium intermediate (cf 16, Scheme 7.9) occurs from the less hindered side and results in the preferential formation of the (E)-ketene N,0-acetal. This kinetic intermediate then undergoes rearrangement...

As in the case of all variations of the Clasien rearrangement, the [3,3]-sigmatropic process is routinely applied for the construction of stereogenicity at quaternary carbon centers. During studies toward the total synthesis of meloscine, orthoester Johnson-Claisen rearrangement was utilized as the key bond formation event when many other attempts to construct the C5 quaternary stereocenter in this sterically-demanding environment failed. Treatment of 351 with trimethyl orthoacetate at elevated temperature readily afforded the ester 352 with moderate diastereoselection." ... 

Tsunoda has rationalized a role for chelation with preferential formation of the Z-enolate 397 from Y-crotyl glycolamide 395 and glycinamide 396. At elevated temperature, the (. -ketene iV, 0-acetal 397 exhibits a facile aza-Claisen rearrangement with excellent syn selectivity. ... 

Cycloadditions. Addition of diethyl azodicarboxylate or related derivatives to polyenes proceeds easily. Further examples of this important route are shown in Scheme 12. The ease with which these adducts may undergo Claisen rearrangement has been further studied. " Rearrangement is facilitated by ring strain and also by electron release from N-substituents (48) is stable even at elevated temperatures. The rearrangement is acid-catalysed. 

The Claisen rearrangement of allyl phenyl ether in a microflow at elevated temperatures has been studied. ... 

The N,N-dimclhylkclcniminium cation (46) is not formed directly from DMAc, but via its enol form (52), see Scheme 19. The formation of the enol form (imine form) is strongly facilitated by the presence of lithium ions, which coordinate to the amide oxygen. Also the intermediacy of enol precursor 52 was proven by means of trapping reactions in the presence of allyl alcohol as the trap, the enol 52 formed an allyl enol ether, which at the prevailing elevated temperatures immediately underwent a Claisen-type rearrangement to produce 4-pentenoic acid N,N-dimethylamidc (53) (Scheme 20). This... 

Reduction of aldehyde (72) to its alcohol (74 Scheme 6) followed by rearrangement with acetal (68) at 110 C affords a 1 1 mixture (30% yield) of the initial Claisen rearrangement product (76) and the tandem Cope-Claisen product (75) that is formed from (76). These conditions illustrate the ease with which the Cope rearrangement can occur when a carbonyl function is present as a substituent. Once again, elevated temperature is required for the unsubstituted Cope transformation, (75) to (77). These operations provide another example of the iterative introduction of ( )-isoprene units into a growing chain. 

Eilbracht et al. have developed rhodium- or ruthenium-catalyzed one-pot synthesis of cyclopentanones from allyl vinyl ether via tandem Claisen rearrangement and hydroacylation [109-111]. This protocol requires elevated temperature (140-220°C) and also requires alkyl or aryl substituents at the terminal position of the allylic double bond to prevent undesirable double bond migration in the intermediary formed, unsaturated aldehyde. 

---