Allyl vinyl ethers Claisen rearrangement substrates

The experimental KIEs were determined for the aliphatic Claisen rearrangement in p-cymene at 120°C and for the aromatic Claisen rearrangement either neat at 170°C or in diphenyl ether at 220°C. Changes in 2H, 13C or 170 composition were determined for unreacted substrates. For carbon analysis of allyl vinyl ether the C5 carbon was used as an internal standard. The C4 atom and rneta aryl protons were used as references in analysis of allyl phenyl ether. The 170 analysis was based on a new methodology. The results are summarized in Table 1, along with predicted isotope effects calculated for experimental temperatures by means of different computational methods. The absolute values of predicted isotope effects for C4 and C5 atoms varied with theoretical level and all isotope effects were rescaled to get reference effects equal to 1.000. 

In accessing chiral allyl vinyl ethers for Claisen rearrangement reactions, Nelson et al. employed the iridium-mediated isomerization strategy. Thus, the requisite enantioenriched diallyl ether substrate 28 was synthesized via a highly enantioselective diethylzinc-aldehyde addition protocol10 (Scheme 1.1k). The enantioselective addition of Et2Zn to cinnamaldehyde catalyzed by (—)-3-exo-morpholinoisobomeol (MIB 26)11 provided an intermediate zinc alkoxide (27). Treatment of 27 with acetic acid followed by 0-allylation in the presence of palladium acetate delivered the 28 in 73% yield and 93% ee. Isomerization of 28 with a catalytic amount of the iridium complex afforded the allyl vinyl ether... 

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. ... 

A series of c/s-substituted allyl-a-trimethylsilylvinyl ethers was also investigated with the same catalyst (f )-98 [25,26]. The data in Table 3 reveal that the enantiomeric purity of the product obtained from asymmetric Claisen rearrangement of the cis-allyl vinyl ethers 104 is not quite as high as from that of the corresponding trans-allyl ethers 102. It was, however, surprising to find that the cis and tram isomers both gave the same enantiomer of the product for all the substrates in Table 3. 

Although the Claisen rearrangement was readily promoted, even by i-BusAl, when large allyl vinyl ethers were used [191], more useful methods characterized by substrate generality, including use of smaller substrates, had remained challenging. Claisen rearrangement is believed to proceed via a six-membered transition state. 

Optically pure aluminum reagent (R)-151 was synthesized from 1 equiv. each of (R)-(-i-)-3,3 -bis(triarylsilyl)-l,l -bi-2-naphthol and MejAl [196], on the basis of the structure of MAPH [197]. Chiral (R)-151 is an excellent promoter of the asymmetric Claisen rearrangement of allyl vinyl ethers 152 or 153 which have bulky substituents such as trialkylsilyl- or trialkylgermanium groups, but is totally ineffective for sterically less hindered substrates (Scheme 6.152). 

Vinylic ether-containing Claisen rearrangement substrates may be generated using syn-elimination reactions of sulfoxides, selenoxides, and selenones. 2-(Arylsulfinyl)ethyl ethers are particularly useful substrates in these reactions because of their ready availability by nucleophilic addition of allylic alcohols to commercially available phenylsulfinylethene. Scheme 13.27 shows a typical synthetic context for this chemistry, involving the stereospecific introduction of quaternary centers from easily accessed allylic alcohol precursors." ... 

Vinylic ether-containing Claisen rearrangement substrates may be generated in some cases by 0-allylation reactions of ketones if there is an intrinsic bias in the reactivity of the derived... 

In the transition state for the asymmetric Claisen rearrangement of allyl vinyl ether 7c with (J )-ATBN 5a, the one conformation of the ether substrate is the matched system for the Cj-symmetric molecular cleft of the chiral aluminum reagent 9, which gives the (S)-product (Fig. 2.3). Increased enantioselectivity using... 

Recently, Hiersemann reported the first catalytic enantioselective Claisen rearrangement (Scheme 2.4) [11]. The 2-alkoxycarbonyl-substituted allyl vinyl ethers 11 are reactive under the Lewis acid catalysis. Therefore, the Claisen rearrangements proceed catalytically [12]. Usually the Lewis-acid-catalyzed Claisen rearrangement does not proceed catalytically because of a higher affinity of the carbonyl product for the Lewis acids than the ether substrate. But this 2-alkoxycarbo-nyl-substituted substrate 11 can coordinate to metals in a bidentate fashion. This 2-alkoxycarbonyl substrate has higher affinity for Lewis acidic Cu complexes than the simple ether substrate. In this system, chiral copper (II) bisoxazoline Cu (box) complex 13 is effective for the enantioselective Claisen rearrangement. 

Two new routes to allyl vinyl ethers, suitable substrates for Claisen rearrangement, are summarized in Scheme 41 and equation (22) one involves copper-catalysed solvolytic cleavage by an allylic alcohol of (E)-alkenylpentafluorosili-cates available from hydrosilylation of alkynes," and the other is based on the base-promoted reaction of dimethyl diazomethylphosphonate with aliphatic ketones in the presence of an allylic alcohol." Electrolytic synthesis of allylic ethers direct from alkenes has been discussed earlier in this Report (Scheme 11). ... 

In 1990, Yamamoto and Maruoka reported the first example of chiral aluminum Lewis acid-catalyzed asymmetric Claisen rearrangement (Scheme 6.162) [192]. Since chiral Lewis acids (2a) and (2b) derived from 3,3 -substituted BINOL derivative (1) exists as a mononuclear complex, high catalytic activity was realized. In this reaction, simple allyl vinyl ethers gave only poor results, although silylated substrates resulted in good enantioselectivity. 

Later, Yamamoto and Maruoka reported improved Lewis acids (153b) and (153c), namely, aluminium tris (2-a-naphthyl-6-phenylphenoxide) (ATNP) and aluminium tris (l-a-naphthyl-3-phenylnaphthoxide) (ATBN), respectively (Scheme 6.163) [192d, 193]. These Lewis acids effectively catalyze asymmetric Claisen rearrangement of simple allyl vinyl ether substrates without a substituent on the vinyl group. 

A general advantage of this acetal, which undergoes hydrolysis at approximately 10 times the rate of THP, " is that it does not confer an additional diastereomeric center to the protected substrate. Access to allyl vinyl ethers for subsequent Claisen rearrangements " is illustrated in eq 2. 

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