Ethers allenyl

Kanematsu s group used a combination of an intramolecular [2+2] cycloaddition of an allenyl ether 4-202 followed by a [3+3] sigmatropic rearrangement (Scheme 4.44) [70]. The substrate for the domino reaction can be obtained in situ by treat-... 

A one-pot three-step conversion of aryl fluorides to phenols based on a consecutive nucleophilic aromatic substitution/isomerization/hydrolysis sequence has been reported by Levin and Du (Scheme 6.126) [256], The authors discovered that 2-butyn-l-ol can function as a hydroxyl synthon through consecutive SNAr displacement, in situ isomerization to the allenyl ether, and subsequent hydrolysis, to afford phenols rapidly and in good yields. In most cases, excesses of 2-butyn-l-ol (1-2 equivalents) and potassium tert-butoxidc (2-4 equivalents) were required in order to achieve optimum yields. 

Vinylidenecarbene or allenylidene3 (R)2C=C=C has a lance-shaped, unsubstituted and sp-hybridized carbene center and, therefore, will not be easily subject to steric hindrance in its insertion reactions. On this assumption, (2-methyljpropenylidenecarbene or its carbenoid was chosen as a prototype of typical vinylidenecarbenes and its insertion reaction with several different types of alkoxides was investigated by employing two methods (A and B, Scheme 10) for carbene generation.20 The insertion products 20 were obtained almost exclusively except lithium allyloxide (Table 4, entry 10).21 By-products such as propargyl ether and allenyl ether were not formed at all. To be noted here, in... 

In this approach, the glycosyl donor and the glycosyl acceptor are linked by the 2-OH of the donor and the free OH of the acceptor. It is one of the most predictable and reliable methods for achieving 1,2-cis stereocontrol. Acetals, mixed p-methoxybenzylacetals and silicon tethering have been widely used as well as iodonium mediated tethering acetals derived from vinyl, allyl and allenyl ethers. These methodologies have been revised.6,76... 

These allenes are very important for organic synthesis and their use is discussed in Chapter 8. For their synthesis usually a strong base is needed, typically KOtBu. There are many examples most of them cover the isomerization of a propargylic ether to the corresponding allenyl ether. 

The competition between a propargylic ether and a teriary propargyhc amine provided an allenyl ether rather than an allenylamine [182], The reaction was also successful with propargyl allyl ethers [232]. An additional ester group in the propargylic position is tolerated [233], and consequently the reaction also works with esters of propargyhc alcohols [234—236]. In the past 4years, several derivatives of carbohydrates were converted successfully [217, 237-241] two examples are the isomeriza-tions of enantiomerically pure 98 [242] and 100 [217, 243] (Scheme 1.43). 

In the [4 + 2] cycloadditions discussed so far, the enol ether double bond of alkoxyallenes is exclusively attacked by the heterodienes, resulting in products bearing the alkoxy group at C-6of the heterocycles. This regioselective behavior is expected for [4+2] cycloadditions with inverse electron demand considering the HOMO coefficients of methoxyallene 145 [100]. In contrast, all known intramolecular Diels-Alder reactions of allenyl ether intermediates occur at the terminal C=C bond [101], most probably because of geometric restrictions. 

Tius and co-workers investigated a number of cationic cyclopentannelations of allenyl ethers [113] and found that 1-lithio-l-alkoxyallenes 180 react with a,/3-unsatu-rated carbonyl compounds 181 leading to highly functionalized cyclopentenones 182 (Scheme 8.44). The primary products are a-allenyl ketones 183, which form pentadienyl cations 184 by protonation. The latter undergo a thermally allowed 4jt-conrotatory ring closure to intermediates 185, which with elimination of R1 finally lead to the expected products 182 (Scheme 8.45). 

Allenyl ethers are useful key building blocks for the synthesis of a-methylene-y-butyrolactones [129, 130], The synthesis of the antileukemic botryodiplodin was accomplished with the crucial steps briefly presented in Scheme 8.56. Bromoallenyl ethers 225 were easily prepared by base-induced isomerization from the corresponding /3-bromoalkyl alkynyl ether compounds and then subjected to electrophilic bro-mination with NBS. The resulting acetals 226 were converted into 2-alkoxy-3-methy-lenetetrahydrofurans 227 by dehydrohalogenation of the alkenyl bromide unit to an alkyne and subsequent radical cyclization employing tributyltin hydride [130],... 

Protonation of 1,2-allenyl ethers ultimately delivers ,/)-unsaturated enones or enals 83-87 [41]. 

The protonated 1,2-allenyl ether can also be attacked by nucleophiles such as thiols to afford 3-methoxy-2-butenyl sulfide 97 and 3-methoxy-3-thiophenyl-l-butene... 

Electrophilic addition of PhI(OAc)2 to 1,2-allenyl ether led to the formation of 3-acetoxy-3-alkoxy-l-propyne [51]. 

The CuBr-catalyzed reaction of a Grignard reagent with 1,2-allenyl ether in Et20 at 20 °C afforded terminal alkynes [53]. 

Protonation of triazole-substituted 1,2-allenyl ether 237 affords the ,/i-unsaturated... 

Intramolecular [4+2]-cycloaddition reactions, which involve base-induced isomerization of a propargyl ether to an allenyl ether, have been extensively studied. Treatment of 157 with a base caused an intramolecular Diels-Alder reaction of the intermediate allenyl ether to give tricyclic compounds 158 [131]. An asymmetric synthesis of benzofuran lactone 159 was achieved by an analogous procedure [132],... 

The addition of allenyl ether-derived anions to Weinreb [4] or to morpholino amides [5] follows a slightly different pathway (Eq. 13.2). For example, the addition of lithioallene 6 to Weinreb amide 7 at -78 °C, followed by quenching the reaction with aqueous NaH2P04 and allowing the mixture to warm to room temperature leads to cyclopentenone 9 in 80% yield [6]. The presumed intermediate of this reaction, allenyl vinyl ketone 8, was not isolated, as it underwent cyclization to 9 spontaneously [7]. These are exceptionally mild conditions for a Nazarov reaction and are probably a reflection of the strain that is present in the allene function, and also the low barrier for approach of the sp and sp2 carbon atoms. What is also noteworthy is the marked kinetic preference for the formation of the Z-isomer of the exocyclic double bond in 9. Had the Nazarov cyclization of 8 been conducted with catalysis by strong acid, it is unlikely that the kinetic product would have been observed. 

The alkyl allenyl ethers whose chemistry has been discussed are readily prepared and are useful for the synthesis of diverse cyclopentenones, as racemates or in enan-tiomerically enriched form. It is worth noting that silyl allenyl ethers allow entry into a distinct mechanistic manifold [16]. Triisopropylsilyloxyallene 47 can be deprotonat-... 

Allenyl ethers 202, which are easily accessible by the methods described in Chapter 1, consequently lead to cyclic ethers 203. The alkoxyallenes were much more reactive than the alkylallenes from the previous example. Thus the amount of catalyst could be reduced to 0.1mol% and 820 turnovers were reached. Five- to seven-membered rings were isolated (Scheme 15.65) [131],... 

Pyridines with an allenyl ether group and an iodine atom substituted on the ring undergo a cyclization reaction to afford furo[3,2-3]pyridine derivatives in moderate yields (Equation 49) <2001T7729>. 

The rearrangement occurs more readily when activating groups (aryl, carboxyl, etc.) are attached to the triple bond. Jacobs [38] reports that a reaction involving adsorption of an acetylenic compound on an active basic surface has led to the practical synthesis of arylallenes, allenyl ethers, allenyl halides, and other substituted allenes. 

Mono- and di-alkylated furans were synthesized in a one-pot preparation from 2-propynyl-2-tetrahydropyranyl ether (106), butyllithium and formaldehyde. The intermediate allenyl ether (107) presumably cyclizes via a 2-(2-tetrapyranyloxy)-2,5-dihydrofuran (108) to afford the heterocycle (109) (79AG(E)875). In a similar manner, singly and doubly branched tetrahydropyranyloxybutynolates afforded the substituted furans (110) (Scheme 20). The thermocatalytic isomerization of ethyl l-methyl-2-phenylcyclopropene-3-carboxylate yielded the furan, possibly by a 1,3-sigmatropic displacement step or by a non-concerted biradical intermediate (75T2495). 

Allenylation of acetals TiCl4 catalyzes a reaction of propargylsilanes with acetals to provide a-allenyl ethers in good yield. 

However, the site of protonation changes to the central catbon when electron-donating substituents such as acetates, alkoxides, arenes and fluoride are attached to the allene moiety. Thus, the hydration of allenyl ethers provides unsaturated aldehydes showing deuterium incorporation at the central carbon (equation 199).300... 

The most versatile synthesis of w./i-unsaUi rated acyl silanes involves the use of allene methodology, developed by a number of groups14,22. Deprotonation and silylation of allenyl ethers followed by hydrolysis gives rise directly to ,/3-unsaturated acyl silanes via their enol ethers, 1-alkoxy-l-trimethylsilylallenes (Scheme 43). Indeed, the first example of an a,/l-unsaturated acyl silane was prepared by such a route223, as was the first example of an allenic acyl silane (from a l-trimethylsilyl-l-trimethylsilyloxy-l,2,3-alkatriene)22b. 

In a further development of this approach, the synthesis of cr,/J-acetylenic acyl silanes has been achieved as shown in Scheme 4514. Oxidation of the 3-selenenyl allenyl ethers (16) with m-chloroperbenzoic acid at —78 °C gave the corresponding unstable selenoxides, which underwent in situ [2,3] sigmatropic shift producing acetals (17). Loss of selenenyl ester on work-up gave the cr,/J-acetylenic acyl silanes in ca 50% yields. 

The facility of these reactions was attributed to the favorable geometry of the allenyl ether for intramolecular Diels-Alder reactions, compared with that of the propargyl ether. These methodologies were used in a new synthesis of a naturally occurring furocoumarin, psoralen 308, which is of interest because of its unique photoreactions with DNA and its utility as a phototherapeutic agent. 

Even if the SMS reaction typically involves allylsilanes, carbonyls and alcohols (or silyl ethers), some transformations can be considered as belonging to the same family. For example, in 2001, Yokozawa et al. described [43] a three-component reaction between aldehydes 6, alkoxysilanes 38 and propargylsilane 88 (instead of allylsilane). Tritylperchlorate was used as the catalyst and a-allenyl ethers 89 were... 

Nagashima S, Kanematsu K (1990) A synthesis of an optically active forskolin intermediate via allenyl ether intramolecular cycloaddition strategy. Tetrahedron Asymmetry 1 743-749... 

Related ethoxyethyl805,1062- 065 and methoxymethyl827,1066-1082 allenyllithiums 739 and 740, respectively, can be prepared by deprotonation of the corresponding allenyl ethers with n-BuLi in THF or THF-ether (1 1), respectively, at —78 to — 95 °C. The anion... 

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