Claisen rearrangement intramolecular

Scheme 32 Sequential Claisen rearrangement-intramolecular Heck reaction [84]...

An iridium(lll)-catalyzed tandem Claisen rearrangement-intramolecular hydroaryloxylation protocol has been described that allows the transformation of allyl aryl ethers to dihydrobenzofurans under mild conditions (Scheme 95) <2005TL1237>. An in rl/ -generated PPh3AuOTf complex also proved to be an efficient catalyst for this transformation <2006SL1278>. 

In K.C. Nicolaou s biomimetic synthesis of 1-O-methylforbesione, the construction of the 4-oxatricyclo[4.3.1.0]decan-2-one framework was achieved by using a double Claisen rearrangement that was followed by an intramolecular Diels-Alder reactionJ This one-pot biomimetic double Claisen rearrangement/intramolecular Diels-Alder reaction cascade afforded the natural product in 63% yield. 

Kim, D., Shin, K.J., Kim, I.Y., and Park, S.W., A total synthesis of (-)-reiswigin A via sequential Claisen rearrangement-intramolecular ester enolate alkylation. Tetrahedron Lett., 35, 7957, 1994. 

For a consecutive electroeyelic ring closure Claisen rearrangement-intramolecular ami-nation process see refs 206 and 207. For studies on the sequential Claisen rearrangement of methyl-3-aryloxy-2-(aryloxymethyl)prop-2-enoates see ref 208 and for the base-catalyzed aromatic Claisen rearrangement of 3-hydroxyphenyl allyl ethers, cf. ref 209. 

Similarly, the substitution pattern determines the rcgioselectivity in the tandem Claisen rearrangement-intramolecular Diels-Alder reaction 283. The double-bond geometry, however, is still E. 

Scheme 13.3S Synthesis of basiliolides using a Claisen rearrangement-intramolecular Diels-Alder strategy.

Scheme 2.7 Stereochemical course of the sequential Claisen rearrangement intramolecular carbonyl-ene reaction.

Scheme 13.20 Total synthesis of basiliolide B (135) by using a sequential Ireland-Claisen rearrangement/intramolecular pyrone Diels-Alder cycloaddition.

The most recent, and probably most elegant, process for the asymmetric synthesis of (+)-estrone appHes a tandem Claisen rearrangement and intramolecular ene-reaction (Eig. 23). StereochemicaHy pure (185) is synthesized from (2R)-l,2-0-isopropyhdene-3-butanone in an overall yield of 86% in four chemical steps. Heating a toluene solution of (185), enol ether (187), and 2,6-dimethylphenol to 180°C in a sealed tube for 60 h produces (190) in 76% yield after purification. Ozonolysis of (190) followed by base-catalyzed epimerization of the C8a-hydrogen to a C8P-hydrogen (again similar to conversion of (175) to (176)) produces (184) in 46% yield from (190). Aldehyde (184) was converted to 9,11-dehydroestrone methyl ether (177) as discussed above. The overall yield of 9,11-dehydroestrone methyl ether (177) was 17% in five steps from 6-methoxy-l-tetralone (186) and (185) (201). 

The stereochemical outcome of the reaction is determined by the geometry of the transition state for the Claisen rearrangement a chairlike conformation is preferred,and it proceeds strictly by an intramolecular pathway. It is therefore possible to predict the stereochemical course of the reaction, and thus the configuration of the stereogenic centers to be generated. This potential can be used for the planning of stereoselective syntheses e.g the synthesis of natural products. 

For example /-butyl phenyl ether with aluminium chloride forms para-t-butyl phenol155. Often the de-alkylated phenol is also formed in considerable quantity. The reaction formally resembles the Fries and Claisen rearrangements. Like the Fries rearrangement the question of inter- or intramolecularity has not been settled, although may experiments based on cross-over studies156, the use of optically active ethers157 and comparison with product distribution from Friedel-Crafts alkylation of phenols158 have been carried out with this purpose in view. 

The stereoselectivity of silyl ketene acetal Claisen rearrangements can also be controlled by specific intramolecular interactions.246 The enolates of a-alkoxy esters adopt the Z-configuration because of chelation by the alkoxy substituent. 

A solvent-free synthesis of benzo[b]furan derivatives 10-79, a class of compounds which is often found in physiologically active natural products, was described by Shanthan Rao and coworkers. These authors heated phosphorane 10-71 for 8 min in a microwave oven and obtained the benzo[b]furan 10-74 in 73% yield (Scheme 10.18) [25]. The sequence is initiated by an intramolecular Wittig reaction, providing alkyne 10-72 this underwent a subsequent Claisen rearrangement to give the intermediate 10-73. Also in this case, normal oil-bath heating gave much lower yields (5%) of the desired product the authors hypothesize that the micro-... 

Claisen rearrangement. As for the mechanism, the reaction begins with intramolecular cyclopropanation the resulting bicyclo[2.1.0]pentan-2-one then undergoes fragmentation to a p,y-unsaturated ketene which finally is trapped by the added alcohol to afford a p,y-unsaturated ester (Scheme 41). The intermediates could be observed in selected cases. 

In 1975, van der Baan and Bickelhaupt reported the synthesis of imide 37 from pyridone 34 as an approach to the hetisine alkaloids, using an intramolecular alkylation as the key step (Scheme 1.3) [23]. Beginning with pyridone 34, alkylation with sodium hydride/allyl bromide followed by a thermal [3,3] Claisen rearrangement gave alkene 35. Next, formation of the bromohydrin with A -bi omosuccinimide and subsequent protection of the resulting alcohol as the tetrahydropyranyl (THP) ether produced bromide 36, which was then cyclized in an intramolecular fashion to give tricylic 37. 

An intramolecular nitrone 1,3-dipolar cycloaddition reaction to give 46 from 45 followed by reductive N-O bond cleavage afforded a stereoselective synthesis of the tetrahydro 177-1-benzazepines 47 the nitrone precursors 44 were prepared in turn by a Claisen rearrangement from an IV-allylamine <06SL2275>. 

The base-catalyzed intramolecular cyclization of appropriately substituted 4-alkyn-1-ols, followed by in situ Claisen rearrangement, has been investigated by Ovaska and coworkers (Scheme 6.85) [179]. The tandem cydization-Claisen rearrangements were best carried out in N,N-dimethylformamide or phenetole as solvent in the pres-... 

A short total synthesis of racemic 7-epi-/3-bulnesene was achieved, in which vinyl cerium 23 was used for the introduction of a three-carbon unit to a ketone 22 to afford tertiary alcohol 24, the substrate for the key intramolecular cyclization/Claisen rearrangement sequence (Scheme 8).14... 

Some other ring expansions involving the intramolecular amino Claisen rearrangement of vinylarylaziridine [ 123], the Diels-Alder reaction of indoles with acetylene derivative [124-127] and the dibromocarbene insertion into quinoline enol ethers [ 128] have been used to prepare 1-benzazepines. On the other hand, treatment of 3-chloro-3-phenyl-l,2,3,4,5,6-hexahydro-l-benz-azocin-2-ones with piperidine causes a ring contraction to give 2-phenyl-2-(l-piperidinylcarbonyl)-2,3,4,5-tetrahydro-l//-l-bcnzazepines in an excellent yield [23]. 

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