Ethers, allyl vinyl ether synthesis

Cu-catalyzed domino reactions have been used for the synthesis of carbocycles, as well as for heterocycles such as indoles, benzoxazoles, and quinoxalines. A very useful process is also the combination of the formation of allyl vinyl ethers, followed by a Claisen rearrangement. 

Sattelkau and Eilbracht90 have exploited the Claisen rearrangement of allyl vinyl ethers in their synthesis of several spiro compounds. As shown below in equation 62, 7,9-dimethyl-l,4-dioxa-spiro[4,5]decan-8-one, 118, was converted to a ,/J-unsaturated ester 119 which was reduced to allyl alcohol 120906. Allyl vinyl ether 121 underwent a rhodium-catalyzed Claisen rearrangement to afford 7r,13r-dimethyl-l,4-dioxa-(8rC9)-dispiro[4.2.4.2]tetradecan-10-one (122) in 36% yield. 

The Claisen rearrangement of allyl vinyl ethers is a classic method for the stereoselective synthesis of y,J-unsaturated esters. The allylic C-H activation is an alternative way of generating the same products [135]. Reactions with silyl-substituted cyclohexenes 197 demonstrate how the diastereoselectivity in the formation of 198 improves (40% to 88% de) for the C-H insertion reactions as the size of the silyl group increases (TMS to TBDPS) (Tab. 14.14). Indeed, in cases where there is good size differentiation between the two substituents at a methylene site, high diastereo- and enantioselectivity is possible in the C-H activation. 

The use of the Claisen rearrangement and several other methods for the stereoselective synthesis of trisubstituted olefins has been reviewed.6 In allyl vinyl ethers of type A, the stereochemistry of the rearrangement is determined largely... 

An aluminium-catalysed tandem Claisen-ene sequence has been developed for the synthesis of homoallylic alcohols (89) and thence a-methylene-y-butyrolactones (90) in good overall yields. Extensive investigation has revealed that Et2AlSPh catalyses Claisen rearrangement of ft -substituted allyl vinyl ethers (85) into 0,5-aluminium... 

The Claisen rearrangement was used in the asymmetric total synthesis of (+)-9(ll)-dehydroestrone methyl ether (5), a versatile intermediate in the synthesis of estrogens5 (Scheme 1. If). The key feature of the synthesis is the successful development of the asymmetric tandem Claisen-ene sequence. Thus, a solution of the cyclic enol ether 6 in toluene was heated in a sealed tube at 180 C for 60 hours to afford the product 9 in 76% isolated yield after deprotection of the silyl enol ether. The Claisen rearrangement of the allyl vinyl ether 6 occurred stereoselectively to give an intermediate (7), in which the 8,14-configuration was 90% syn. The stereoselectivity in the Claisen rearrangement can be explained... 

A mercury-free route to allyl vinyl ethers that relies on the Michael addition of allyl alcohols to unsubstituted alkenyl sulfoxides, followed by thermal loss of sulfenic acid and concurrent Claisen rearrangement has been described [145]. This methodology has been applied to the synthesis of isocar-bacyclin [146]. Posner reported an acid-catalyzed protocol that produces conjugated dienoate esters from allylic alcohols and a sulfinyl orthoester [147]. Additionally, the use of propargyl alcoholates and a chloro alkenyl sulfox-... 

Mandai, Saito and cowoikers recently described a new synthesis of isocaibacyclin, which features a crucial one-pot, three-step transformation tandem tertiary allyl vinyl ether formation, Claisen rearrangement, and ene cyclization led from alcohol (57) directly to bicyclo[3.3.0]octane (59 heme 10). Clearly, due to improvements in the preparation of Ae allyl vinyl ether moiety, there is a trend even in the classical Qaisen rearrangement to taclde more complex structural challenges successfully. 

Synthesis ofkarahanaenaue. The ionic reaction of NBS in CCI4 at room temperature with a y-ethylcnic tertiary alcohol leads to an -bromotetrahydrofurane. The reaction has been used in a convenient synthesis of karahanaenone (4), a constituent of hop oil, from linalool (1). Thus reaction of (1) with NBS affords 2-mcthyl-2-vinyl-5-(l-bromo-l-methylethyl)tetrahydrofurane (2) in 85% yield. Dehydrohalogena-tion of (2) with collidine at 110 leads to the allyl vinyl ether (3), which immediately... 

Olefin isomerization catalyzed by ruthenium alkylidene complexes can be applied to the deprotection of allyl ethers, allyl amines, and synthesis of cyclic enol ethers by the sequential reaction of RCM and olefin isomerization. Treatment of 70 with allyl ether affords corresponding vinyl ether, which is subsequently converted into alcohol with an aqueous HCl solution (Eq. 12.37) [44]. In contrast, the allylic chain was substituted at the Cl position, and allyl ether 94 was converted to the corresponding homoallylic 95 (Eq. 12.38). The corresponding enamines were formed by the reaction of 70 with allylamines [44, 45]. Selective deprotection of the allylamines in the presence of allyl ethers by 69 has been observed (Eq. 12.39), which is comparable with the Jt-allyl palladium deallylation methodology. This selectivity was attributed to the ability of the lone pair of the nitrogen atom to conjugate with a new double bond of the enamine intermediate. 

Recently, Claisen rearrangement of allyl-vinyl ether prepared from glycal ester with Tebbe reagent was reported [91]. In contrast to the Ireland-Claisen rearrangement, in principle, a non-enolizable ester can be employed (O Scheme 63). This method was applied for the synthesis of C-disaccharide. 

The asymmetric total synthesis of the putative structure of the cytotoxic diterpenoid (-)-sclerophytin A was realized via a Tebbe-Claisen rearrangement of a tricyclic lactone precursor in the laboratory of L.A. Paquette/ The tricyclic lactone was subjected to the Tebbe methylenation protocol to provide the allyl vinyl ether that was then heated to 130-140 °C in p-cymene to undergo the Claisen rearrangement in good yield. 

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. 

Panek et al. introduced the synthesis of optically active crotylsilanes by Claisen rearrangement of allyl vinyl ethers derived from homochiral y-silylated allyl alcohols (Scheme 10.141) [393]. These allylsilanes have been used for highly diastereo-and enantioselective allylation of aldehydes and acetals [334], which enables efficient syntheses of complex natural products [394]. 

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