Acryloyl lactates

Chelation can favor a particular structure. For example, O-acryloyl lactates adopt a chelated structure with TiCl4.13... 

Prompted by the X-ray studies of the acryloyl lactate-TiCU complex (380a), commercially available pantolactone was chosen as an auxiliary aiming to facilitate entropically the formation of a seven-mem-bered titanium chelate (385). Indeed, using 0.1-0.75 mol equiv. of TiCU the acrylate and crotonate of (/ )-pantolactone (384) underwent smooth addition of cyclopentadiene, butadiene and isoprene to give adducts (386) and (387) in ratios of >93 <7 (Scheme 94, Table 24, entries a-d). Opposite product ratios were obtained using dienophiles (388) derived from (S)-pantolactone (entiy e) or (390) derived from the more readily available A -methyl-2-hydroxysuccinimide (entries f, g). The major products were purified by crystallization and saponified without epimerization (LiOH, THF/water, r.t.) to furnish the corresponding carboxylic acids. 

Some crystal structures of chelate complexes have been reported. An O-acryloyl-lactate-TiCU complex (Fig. 3) [26,27] has rare out-of-plane (Fig. 4) coordination of the acryloyl carbonyl group to the titanium a further study has been conducted [28]. Diethyl phthalate-TiCU [29], l,2-diketone-TiCl4 [25], and achiral [24] or chiral [30] acyloxazolidinone-TiCU complexes have been reported to involve in-plane coordination as shown in Fig. 5. The /S-alkoxyketone-TiCU complex shown in Fig. 6 [31] is characterized by a rare out-of-plane coordination geometry (dihedral bond angle of... 

Figure 6.14. (a-c) Possible conformations of 0-acryloyl lactates coordinated to one or more Lewis acids (after ref. [174]). (d) Stereoview of the crystal structure of 0-acryloyl ethyl lactate TiCU complex (reprinted with permission from ref. 

The lactone of 2,4-dihydroxy-3,3-dimethylpentanoic acid (known as pantolactone) has been successfully employed as a chiral auxiliary in several D-A reactions. For example, in conjunction with TiCl4, it provides a 92% de in the reaction of 2,3-dimethylbutadiene with a-cyanocinnamic acid. The diastereoselectivity is consistent with a chelated structure similar to that shown above for acryloyl lactate. In the absence of TiCl4, this same ester gives a 64% de of the opposite configuration. This... 

Fig. 6.5. Structure of the TiCl4 complex of O-acryloyl ethyl lactate. Reproduced from Angew. Chem. Int. Ed. Engl., 24, 112 (1985), by permission of Wiley-VCH.

The highly ordered cyclic TS of the D-A reaction permits design of diastereo-or enantioselective reactions. (See Section 2.4 of Part A to review the principles of diastereoselectivity and enantioselectivity.) One way to achieve this is to install a chiral auxiliary.80 The cycloaddition proceeds to give two diastereomeric products that can be separated and purified. Because of the lower temperature required and the greater stereoselectivity observed in Lewis acid-catalyzed reactions, the best diastereoselectivity is observed in catalyzed reactions. Several chiral auxiliaries that are capable of high levels of diastereoselectivity have been developed. Chiral esters and amides of acrylic acid are particularly useful because the auxiliary can be recovered by hydrolysis of the purified adduct to give the enantiomerically pure carboxylic acid. Early examples involved acryloyl esters of chiral alcohols, including lactates and mandelates. Esters of the lactone of 2,4-dihydroxy-3,3-dimethylbutanoic acid (pantolactone) have also proven useful. 

Prediction and analysis of diastereoselectivity are based on steric, stereoelectronic, and complexing interactions in the TS.82 In the case of the lactic acid auxiliary, a chelated structure promotes facial selectivity. In the TiCl4 complex of 0-acryloyl ethyl lactate,... 

Pyruvate lactate lactoyl-CoA acryloyl CoA 3-hydroxypropionyl-CoA 3HP 1/0 1-19.9 US7186541 B2 Cargill [27]... 

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