✍ Scribed by Kei Takeda; Ikuhiro Imaoka; Eiichi Yoshii
No coin nor oath required. For personal study only.
The usefulness of Diels-Alder (D-A) reaction in organic synthesis has been attributed to its high stemoselectivity based on endo cycloaddition. which is explained by the concept of secondary orbital overlap in the transition state.1 Exo-mode addition, however, can predominate in some cases,"5 particularly in the combination of cyclopentadiene and methacrylic dienophiles,s but the factors that determine the abnormal addition mode have not been fully understood. td In the course of our synthetic studies on spirotetronic acid containing natural products, we demonstrated that D-A reaction of y-(methylene)tetronate 1 with triene 3 could be used for the direct construction of the subunit structure of kijanolide, though the reaction produced undesired endo adduct in excess (Scheme 1).6 Some two years later, Roush and Brown disclosed that a highly exo-selective cycloaddition could be accomplished by the use of a-(methylene)dioxolanone 2 as a dienophile.sb This sharp contrast in the diastereoselectivities observed with 1 and 2 led us to investigate the D-A reactions of a-substituted acrylates and of a-(methylene)lactones of varying ring size in order to find a general correlation between dienophile structure and endo/exo ratio. As the diene in this study, we made a choice of the particular acyclic diene, 1,6-bis(trimethylsilyloxy)-2.4-hexadiene (4).7 based on, for one thing, the ease in steteochemical assignment of cycloadducts (vide infra). We also considemd an additional advantage in using the linear diene 4 over cyclopentadiene. although the latter has been extensively employed in the stereochemical studies of D-A reaction. Referential exo selectivity in the cycloaddition of cyclopentadiene with methacrylic dienophiles has been believed partly due to a steric repulsion between the diene CH2 and the a-CHs of the dienophiles in the endo transition state,'&**9 the unfavorable steric factor that we wanted to eliminate in the present study. Scheme 1 endolexo = 33 10840 K. TAKEDA et al. We first conducted the D-A reactions betwein a-substituted acrylstes !ke and 4 in odichlorobenxene (1 M for 5, molar ratio of 4/5 = 3.0) at the temperaune of 170 "C where each maction pmceeded atareason- able rate. The ratios of endo products (6a+) and exo products (7~) recokd in Table 1 were estimated by capillary GLC analysis after determination of their stereochemistries by conversion to bicyclic ciAactones @n-e) and dihydroxy ester (Se), respectively, by brief tmatment with p-TsGH in CH&!l2. All the acrylate @a-e) showed en& preference (endo/exo = 59:41 to 7426) in contrast to the exo selectivity reported for the reactions of cyclopentadiene with 2-(trimethylsilyloxy)acrylate (Sb) (endo/exo = 2971)s~ and methacrylate (5e) (endo/exo = 3268)" d OMe e Me ::x HO - 9 G 0 0 oa*
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