Vinyl allyl ethers, enantioselective

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

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

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]. 

Cyclisations onto allylic ethers such as 325 give vinyl-substituted pyrrolidines in good yield.61 Enantioselective versions of similar syntheses of pyrrolidines are discussed below. 

Thus, the kinetic resolution of a variety of pyrans [123] and cyclic allyl ethers (six-, seven- and eight-membered vinyl systems) was investigated [124]. In all cases, a very high enantioselectivity of the remaining starting materials was obtained. 

McDonald RI, Wong GW, Neupane RP, Stahl SS, Landis CR (2010) Enantioselective hydroformylation of N-vinyl carboxamides, allyl carbonates, and allyl ethers using chiral diazaphospholane ligands. J Am Chem Soc 132 14027-14029... 

Bisdiazaphospholanes have been linked to organic resins via the correspond-ingtetraacyl fluoride derivatives (Scheme 2.147) [69]. Compared with the relevant homogeneous catalysts, comparable regio- and enantioselectivities were observed in the AHF of styrene, vinyl acetate, 0-silyl protected allyl ethers, and dihydro-furane. Excellent recyclability with only trace levels of rhodium leaching were reported under batch or flow conditions. In contrast, the silica-bound catalyst I exhibited poorer enantioselectivities. 

Subsequently, the same group demonstrated an asymmetric synthesis of 3-amino aldehydes via catalytic double-bond isomerization/enantioselective aza-Petasis-Ferrier rearrangement reaction (Scheme 2.93) [128]. Similarly, the hemiaminal allyl ether substrates 346 were first isomerized by Ni(II) complexes to stereoselectively form Z-configured vinyl ethers 347, which then underwent a phosphoric acid-catalyzed... 

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. 

Recently, the first examples of catalytic enantioselective preparations of chiral a-substituted allylic boronates have appeared. Cyclic dihydropyranylboronate 76 (Fig. 6) is prepared in very high enantiomeric purity by an inverse electron-demand hetero-Diels-Alder reaction between 3-boronoacrolein pinacolate (87) and ethyl vinyl ether catalyzed by chiral Cr(lll) complex 88 (Eq. 64). The resulting boronate 76 adds stereoselectively to aldehydes to give 2-hydroxyalkyl dihydropyran products 90 in a one-pot process.The diastereoselectiv-ity of the addition is explained by invoking transition structure 89. Key to this process is the fact that the possible self-allylboration between 76 and 87 does not take place at room temperature. Several applications of this three-component reaction to the synthesis of complex natural products have been described (see section on Applications to the Synthesis of Natural Products ). 

A related allylic C-H insertion that has considerable promise for strategic organic synthesis is the reaction with enol silyl ethers [23]. The resulting silyl-protected 1,5-dicarbonyls would otherwise typically be formed by means of a Michael addition. Even though with ethyl diazoacetates vinyl ethers are readily cyclopropanated [l],such reactions are generally disfavored in trisubstituted vinyl ethers with the sterically crowded donor/acceptor carbenoids [23]. Instead, C-H insertion predominates. Again, if sufficient size differentiation exists at the C-H activation site, highly diastereoselective and enantioselective reactions can be achieved as illustrated in the reaction of 20 with 17 to form 21 [23]. 

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. 

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%). 

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... 

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... 

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