Allylic alcohols Claisen rearrangement

A second general approach to allyl /(-lluorovinyl ether intermediates involves the reaction of a /J-fluoro alcoholate with an allylic halide. Claisen rearrangement then produces a-fluoro carbonyl compounds. Although the tremendous rate acceleration caused by a-fluoro substitution in the vinyl fragment is not present here, the rearrangements take place under synthetically useful conditions. 

The substrates for allyl vinyl Claisen rearrangements are conveniently obtained by transetherification of vinyl alkyl ethers with allylic alcohols. Typical examples of this rearrangement are represented in Scheme 2.155. The transformation of allyl vinyl ether 482 into aldehyde 483 illustrates the unique potential of the Claisen rearrangement as a method to prepare angularly substituted derivatives from readily available precursors such as 484, a goal hardly achievable by other routes. Products of this type are used as key intermediates in the syntheses of many natural compounds. ... 

Conjugate addition of vinyllithium or a vinyl Grignard reagent to enones and subsequent oxidation afford the 1.4-diketone 16[25]. 4-Oxopentanals are synthesized from allylic alcohols by [3,3]sigmatropic rearrangement of their vinyl ethers and subsequent oxidation of the terminal double bond. Dihydrojasmone (18) was synthesized from allyl 2-octenyl ether (17) based on Claisen rearrangement and oxidation[25] (page 26). 

A synthetically valuable reaction sequence is the chlorodifluoroacetylation of various substituted allylic alcohols and the subsequent Reformatskii-Claisen rearrangement of the ester thus formed to interesting 2,2-difluoropentenoic acid derivatives [25] (equation H) Comparable sequences have been reported for ally monofluoroacetates [26] and allyl 3,3,3-trifiuoropropanoates [27] (equations 15 and 16). 

A salient structural feature of intermediate 18 (Scheme 2b), the retrosynthetic precursor of aldehyde 13, is its y,r5-unsaturated ester moiety. As it turns out, the Johnson ortho ester variant of the Clai-sen rearrangement is an excellent method for the synthesis of y,<5-unsaturated esters.11 In fact, the Claisen rearrangement, its many variants included, is particularly valuable in organic synthesis as a method for the stereocontrolled construction of trans di- and tri-substituted carbon-carbon double bonds.12,13 Thus, it is conceivable that intermediate 18 could be fashioned in one step from allylic alcohol 20 through a Johnson ortho ester Claisen rearrangement. In... 

N,O-acetal intermediate 172, y,<5-unsaturated amide 171. It is important to note that there is a correspondence between the stereochemistry at C-41 of the allylic alcohol substrate 173 and at C-37 of the amide product 171. Provided that the configuration of the hydroxyl-bearing carbon in 173 can be established as shown, then the subsequent suprafacial [3,3] sigmatropic rearrangement would ensure the stereospecific introduction of the C-37 side chain during the course of the Eschenmoser-Claisen rearrangement, stereochemistry is transferred from C-41 to C-37. Ketone 174, a potential intermediate for a synthesis of 173, could conceivably be fashioned in short order from epoxide 175. 

It is possible to treat ketones with allyl alcohol and an acid catalyst to give y,5-unsaturated ketones directly, presumably by initial formation of the vinylic ethers, and then Claisen rearrangement.In an analogous procedure, the enolates (126) of allylic esters [formed by treatment of the esters with lithium isopropylcyclohex-... 

The reactants can be made from allylic alcohols by mercuric ion-catalyzed exchange with ethyl vinyl ether.220 The allyl vinyl ether need not be isolated and is often prepared under conditions that lead to its rearrangement. The simplest of all Claisen rearrangements, the conversion of allyl vinyl ether to 4-pentenal, typifies this process. 

The mechanism and stereochemistry of the orthoester Claisen rearrangement is analogous to the Cope rearrangement. The reaction is stereospecific with respect to the double bond present in the initial allylic alcohol. In acyclic molecules, the stereochemistry of the product can usually be predicted on the basis of a chairlike TS.233 When steric effects or ring geometry preclude a chairlike structure, the reaction can proceed through a boatlike TS.234... 

Scheme 6.15 gives some representative examples of the orthoester Claisen rearrangement. Entry 1 is an example of the standard conditions for the orthoester Claisen rearrangement using triethyl orthoacetate as the reactant. The allylic alcohol is heated in an excess of the orthoester (5.75 equivalents) with 5 mol % of propanoic acid. Ethanol is distilled from the reaction mixture. The E-double bond arises from the chair TS. 

A. Claisen Rerrangements of Ketene Aminats and Imidates. A reaction that is related to the orthoester Claisen rearrangement utilizes an amide acetal, such as dimethylacetamide dimethyl acetal, in the exchange reaction with allylic alcohols.257 The products are y, 8-unsaturated amides. The stereochemistry of the reaction is analogous to the other variants of the Claisen rearrangement.258... 

Wipf and coworkers used a Claisen rearrangement of allyl phenyl ethers 4-309 followed by an enantioselective carboalumination using the chiral Zr-complex 4-310 and trimethyl aluminum (Scheme 4.67) [104]. After an oxidative work-up of the intermediate trialkylalane, the corresponding alcohols 4-311 were obtained with up to 80% ee and 78% yield. One can also transfer an ethyl group using triethyl aluminum with even better ee-values (up to 92%), but the yields were rather low (42%) due to a more sluggish oxidative cleavage of the Al-C bond. 

As shown earlier in many examples, the Claisen rearrangement of allyl vinyl ethers also provides a very powerful method for carbon-carbon bond formation in domino processes. Usually, the necessary ethers are formed in a separate step. However, both steps can be combined in a novel domino reaction developed by Buchwald and Nordmann [306]. This starts from an allylic alcohol 6/4-102 and a vinyl iodide 6/4-103, using copper iodide in the presence of the ligand 6/4-104 at 120 °C to give 6/4-105 (Scheme 6/4.25). The reaction even allows the stereoselective formation of two adjacent quaternary stereogenic centers in high yield. 

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. 

The [3, 3] sigmatropic rearrangement of allyl vinyl ethers is known as Claisen rearrangement. Allylic alcohols can be converted to allyl vinyl ethers by mercuric acetate catalysed exchange with ethyl vinyl ether. The allyl vinyl ether need not be isolated because it undergoes rearrangement to 4-pentenal. 

The intermediate product 162, formed from the nudeophilic addition of 1,2-alle-nic phosphonate or 1,2-allenic phosphine oxide with allylic alcohol, would also undergo a Claisen rearrangement to form 2-oxo-5-alkenyl phosphonate or phosphine oxide 163 [85], The rearrangement is accelerated by the carbanionic nature of the intermediate 162. For the conjugate addition step, the reaction temperature is crucial since the reaction at 0 °C afforded mainly /i,y-unsaturated product whereas a,/8-unsaturated products were formed at 20 °C. 

The three-step procedure described for the preparation of the illustrated crotylsilanes is initiated with the hydrosilation of rac-3-butyn-2-ol. This procedure is significantly improved with respect to the positional selectivity of the hydrosilation resulting in exclusive formation of the racemic (E)-vinylsilane, and as a result the present procedure is much more amenable to scale-up than those previously described in the literature.8 The enzymatic resolution of the racemic secondary allylic alcohol (vinylsilane) has also been reported using commercially available lipase extracts. The use of a Johnson ortho ester Claisen rearrangement affords the (E)-crotylsilanes 4 in nearly enantiomerically pure form. 

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