Vinyl allyl ethers, enantioselective Claisen rearrangement

Enantioselective Claisen rearrangement of allyl (a-trimethylsilyl)vinyl ethers in the presence of aluminium binaphthol derivatives gives ft-chiral y, <5-unsaturated acyl silanes with good ee (Scheme 33)114. 

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... 

This system can be applied to the enantioselective Claisen rearrangement of difluoro-vinyl allyl ethers (Eq. 71) [53b]. 

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. 

In 2002, Mamoka et al. reported the enantioselective Claisen rearrangement of allyl vinyl ethers 61 induced by chiral bis-organoaluminum complex 62 (Scheme 44) [77]. Reactions using mono-organoaluminum complex 63 resulted in the decrease of both chemical yields and enantiomeric excess, indicating the importance of the double coordination between carbonyl group and two aluminum centers of 62. 

SCHEME 17 2. Uyeda and Jacobsen s catalytic enantioselective Claisen rearrangement of substituted vinyl allyl ethers. 

Abraham L, Czerwonka R, Hiersemann M. The catalytic enantioselective Claisen rearrangement of an allyl vinyl ether. Angew. Chem. Int. Ed. 2001 40(24) 4700-4703. 

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. 

Claisen rearrangement.1 Claisen rearrangement of simple allyl vinyl ethers effected with (R)- and (S)-l shows low enantioselectivity, but the rearrangement of allyl vinylsilyl ethers results in acylsilanes in high optical yield (80-90%). 

Allylic C-H insertions have been used in key steps of the enantioselective synthesis of the pharmaceuticals (+)-ceitedil (26) [21] and (+)-indatraline (27) [22] (Scheme 11). The allylic C-H insertion reaction is an exciting alternative to the Claisen rearrangement as a rapid method for the synthesis of y,c>-unsaturated ester [23 ]. Similarly, the allylic C-H insertion with vinyl silyl ethers generates protected 1,5-dicarbonyl compounds, a complimentary reaction to the Michael addition [24]. Both types of C-H insertion can be achieved with high diastereoselectiv-ity and enantioselectivity [23, 24]. 

Several chiral organoaluminum Lewis acids catalyze the Claisen rearrangement of achiral allyl vinyl ethers to furnish chiral (3, y-unsaturated aldehydes with good enantioselectivity. Among the most effective catalysts is ATBN-F, a chiral aluminum tris(P-naphthoxide) species prepared from enantiomerically pure binapthol. ... 

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]. 

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... 

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. 

Claisen and related sigmatropic rearrangements have traditionally represented difficult scenarios for enantioselective catalysis. Consequently, Yamamoto s 1990 report that allyl vinyl ethers 97 undergo enantioselective rearrangement in the presence of chiral aluminum complexes 96 constituted a breakthrough in the discipline (Equation 8) [76]. In the presence of 1-2 equiv of the bulky aluminum complex 96, the rearranged products were isolated with impressive yield and enantioselectivity (cf. 98 99% yield, 88% ee). 

---