Modified Claisen Rearrangements

Figure 4.6 Synthesis of the pheromone of Biprorulus bibax employing Claisen rearrangement. Modified by permission of Shokabo Publishing Co., Ltd...

The ester-Claisen rearrangement procedure of Johnson and coworkers1 2 3 was modified for use with cholest-4-en-3/5-ol. 

Rearrangement of aryl propargyl ethers.1 Claisen rearrangement of the naphthyl propargyl ether 1 at 215° results in the benzopyran 2 as the only isolable product (40% yield). Addition of 1 equiv. of CsF results in the benzofuran 3 as the major product, presumably formed via an a-allenyl ketone (a). Related salts such as KF, RbF, or BaF2 are completely ineffective. This modified Claisen rearrangement provides a route to o-hydroxy aldehydes such as 4 from a phenol. 

Claisen Rearrangements. A modified BINOL-derived aluminum reagent is an effective chiral catalyst for asymmetric Claisen rearrangement of allylic vinyl ethers (eq 29). The use of vinyl ethers with sterically demanding C-3 substituents is necessary for the high level of asymmetric induction. 

After this two-step reaction sequence, the modified molecule directly undergoes a rearrangement to give the allyl vinyl ether 24. What kind of functional groups are necessary for a >, >yxQXvo-Claisen rearrangement ... 

Another unprecedented stereochemical control in a Claisen rearrangement was reported recently by Yamamoto using organoaluminum reagents (Scheme 59). Sometimes (e.g. with R = Cu2CH==CH— CsHi i) complete reversal of double bond geometry could be achieved simply by modifying the bulky aluminum catalyst. 

A new perspective was opened up recently when Denmark demonstrated diat with chirally modified phosphoryl-activated allenes an asymmetric induction could be effected. From easily generated allenyl phosphoramidates containing an optically active amino alcohol, the diastereomeric adducts (37) and (39) could be obtained by addition of dlyl alcohol. When the separated adducts were employed in the carb-anionic Claisen rearrangement, a remarkable asymmetric induction (90 10) could be achieved with preferential formation of the diastereomers (38) or (40) respectively, whereas in a thermal reaction no stereoselection was observed (Scheme 63). Another example of an asymmetric induction in Claisen rearrangements is reported by Welch. ... 

In the laboratory of T. Nakai, the asymmetric tandem Claisen-rearrangement-ene reaction sequence followed by a modified McMurry coupling was used to access (+)-9(11)-dehydroestrone methyl ether. The Claisen-ene product was subjected to ozonolysis and epimerization to the 8,14-anf/ configuration. The C-ring was constructed by treating the tricyclic diketo aldehyde with TiCl3-Zn(Ag) in DME to afford the desired final product in 56% yield. 

Details have been published of the total syntheses of velbanamine, isovel-banamine, cleavamine, 18/3-carbomethoxycleavamine, and catharanthine. Rosen-mund s route to the iboga alkaloids has now been appropriately modified to yield ibogamine and ibogaine, in addition to epi-ibogamine, and details of this work are also available. Hydroboration-oxidation of (227), presumably obtained by a thio-Claisen rearrangement [cf. (200)- (201)] affords the alcohol (228) which is a key intermediate in a Kutney-type synthesis of cleavamine however, details of the synthesis are not yet available. ... 

The Claisen rearrangement of the A5-vinyl ether (237) provided the aldehyde (238) which was modified to give the ethynyl derivative (239) and the allene (241) was prepared from the acetoxy-ethynyl derivative (240) through a mixed cuprate-... 

Amauromine, a dimeric indole alkaloid with hypotensive vasodilator properties, was isolated from Amauroascus species (Gymnoascales, Ascomycotina) (267) and Penicillium verrucosum (26S). The structure of this metabolite was determined by chemical and spectroscopic investigations and confirmed by a total synthesis by Takase et aL 268). The symmetrical diketopiperazine made up of two modified tryptophans, each bearing a 1,1-dimethylallyl group at C-3, was synthesized as shown briefly in Scheme 45. The two inverted prenyl groups were introduced simultaneously by a thio-Claisen rearrangement reaction through the sulfonium salt. 

Two groups have reported on the use of the Claisen rearrangement to obtain 2,3-unsaturated C-glycosides. Fraser-Reid and colleagues found the standard reaction applied to derivatives of the allylic alcohol (77) inefficient because of the poor yields of the derived vinyl ethers or because allylic esters e.g. (78) predominated. They were successful, however, in obtaining compounds (79) and (80) by modified procedures (Scheme 5). An alternative synthesis of saturated, and hence unsaturated, C-glycosides was developed as illustrated in Scheme 6. In parallel work Ireland and co-workers used the enol silyl ether approach as shown in Scheme 7 and employed the products in polyether antibiotic syntheses. ... 

An intermediate prepared from isopropylidene-D-glyceraldehyde via a Claisen rearrangement and previously used for the synthesis of some branched-chain fluorinated nucleosides (Vol. 32, p. 272-273), has now been used to make a fluorinated cyclopentane unit, to which was linked 6-chloropurine, thus leading to carbocyclic 2, 3 -dideoxy-4 -fluoro-L-adenosine (161). The same synthetic sequence could be modified to generate, via a metathesis step, an enantiomeric cyclopentane unit, and hence the enantiomer of 161, and equivalent structures with the other nucleobases. ... 

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