Palladium(II)-Catalyzed Enantioselective Synthesis of 2-Vinyl Oxygen Heterocycles

Abstract

2-Vinylchromanes (1), 2-vinyl-1,4-benzodioxanes (2), and 2,3-dihydro-2-vinyl-2H-1,4-benzoxazines (3) can be prepared in high yields (90–98%) and excellent enantiomeric purities (87–98% ee) by [COP-OAc]2-catalyzed cyclization of phenolic (E)-allylic trichloroacetimidate precursors. Deuterium-labeling and computational experiments are consistent with these cyclization reactions taking place by an anti-oxypalladation/syn-deoxypalladation mechanism. 2-Vinylchromanes can be prepared also in good yields and high enantiomeric purities from analogous (E)-allylic acetate precursors, which constitutes the first report that acetate is a competent leaving group in COP-catalyzed enantioselective SN2′ substitution reactions.

Transition‐Metal‐Catalyzed Allylic Substitutions of Trichloroacetimidates

“…This reaction, however, requires use of phenoxides as nucleophiles. To illustrate the utility of [COP‐OAc] 2 ‐catalyzed asymmetric allylic substitution further, Overman extended its scope to phenol nucleophiles,58 including intermolecular59 and intramolecular60 aryl‐ether‐forming reactions from Z ‐ and E ‐configured imidates 61…”

“…In an effort to expand the capabilities of this enantioselective method, the development of the intramolecular variant was pursued (Table 6). 60,62,63 The cyclization of phenolic ( E )‐allyl imidate 88a in the presence of the two COP‐derived catalysts 12 and 81 (Entries 1 and 2) was examined under previously optimized conditions 59. Use of 12 afforded 2‐vinylchromane ( 89a , Entry 1) in 86 % yield and with 89 % ee 60.…”

“…60,62,63 The cyclization of phenolic ( E )‐allyl imidate 88a in the presence of the two COP‐derived catalysts 12 and 81 (Entries 1 and 2) was examined under previously optimized conditions 59. Use of 12 afforded 2‐vinylchromane ( 89a , Entry 1) in 86 % yield and with 89 % ee 60. Although use of the [COP‐NHCOCCl 3 ] 2 complex 81 (Entry 2) provided the desired product 89a in good yield and with high levels of enantioselectivity, the competiting formation of the rearranged trichloroacetamide, in 13 % yield, was also observed 60.…”

“…Use of 12 afforded 2‐vinylchromane ( 89a , Entry 1) in 86 % yield and with 89 % ee 60. Although use of the [COP‐NHCOCCl 3 ] 2 complex 81 (Entry 2) provided the desired product 89a in good yield and with high levels of enantioselectivity, the competiting formation of the rearranged trichloroacetamide, in 13 % yield, was also observed 60. Lowering the catalyst loading to 0.5 mol‐% (Entry 3) did not diminish the yield and enantiomeric purity (91 % and 94 % ee ).…”

“…This intramolecular variant is also suitable for the enantioselective synthesis of both 2‐vinyl‐1,4‐benzodioxane ( 89d ) and 2,3‐dihydro‐2‐vinyl‐2 H ‐1,4‐benzoxazine 89e (Scheme ) in excellent yields and with 94 % and 98 % ee , respectively 60. Unfortunately, the [COP‐OAc] 2 ‐catalyzed intramolecular reaction is not applicable for preparation of 2,3‐dihydro‐2‐vinyl‐2 H ‐1,4‐benzothiapyran ( 89f ).…”