Vares and Rein have developed a powerful approach to tetrahydrofurans
where they coupled an asymmetric Horner–Wadsworth–Emmons (HWE) reaction
with a Pd-catalyzed ring closure to generate cis- and trans-tetrahydrofuran derivatives (Schemes 76 and 77) [82]. From meso-dialdehyde 289, asymmetric HWE
gave E-alkene isomer 291 with high levels of diastereoselectivity. Aldehyde
reduction was followed by pivaloyl migration to afford cyclization precursor
292 in 63 % yield. Pd-catalyzed π-allyl formation and cyclization proceeded
with overall retention of stereochemistry to give 2,5-cis-tetrahydrofuran 293 in
76 % yield.
2,5-trans-Tetrahydrofurans were generated by Vares and Rein through the use of
the corresponding Z-olefin in the Pd-catalyzed cyclization. Asymmetric HWE using
trifluoroethylphosphonate ester 294 gave Z-olefin 295. Reduction of the remaining
aldehyde gave a 1.3:1 mixture of secondary alcohol 296 and the corresponding
primary alcohol. After separation, Pd-catalyzed cyclization resulted in the generation
of 2,5-trans-tetrahydrofuran 297 as the E-olefin isomer.
Enders and coworkers have observed high levels of enantioselectivity from
organocatalytic tandem Michael additions (Scheme 78). Their approach to tetrahydrofurans involved an initial nitrodiene-aldehyde condensation followed by an
intramolecular oxy-Michael addition [83]. As illustrated, the sequence gave 301 in
high diastereo- and enantioselectivity.
9 Miscellaneous Approaches to Tetrahydrofurans
Yamazaki and coworkers have described formal [3+2]-cycloadditions of ethene
tricarboxylates with substituted propargyl alcohols to give methylene tetrahydrofurans (Scheme 79) [84]. Interesting was that the E/Z selectivity of the reaction
depended upon the Lewis acid that was used. Z-Alkene isomers 304 were obtained
in moderate to high yields when triply activated alkene 302 was treated
with propargyl alcohol 303 in the presence of ZnBr 2 , InCl 3 , FeCl 3 , or AlCl 3 salts.
The corresponding E-isomer 308 was obtained when SnCl 4 was used. The authors
speculate that protonation in the SnCl 4 reaction occurs from allenyl species 309
where tin is coordinated to oxygen. Protonation in the Zn-, In-, Fe-, and
Al-catalyzed reactions is thought to occur from the Z-vinyl species 305.
Xi and coworkers have discovered that zirconacyclopentadienes can be used to
generate tetrahydrofurans when they are reacted with aldehydes [85]. The transformation requires the presence of CuCl and two equivalents of aldehyde (Scheme 80).
To explain the process, Xi et al. have proposed a mechanism where zirconacycle
312 reacts with the first equivalent of aldehyde to give 313. Transmetallation with
CuCl and reaction with the second equivalent of aldehyde provides cyclization
precursor 315. Acidic workup and cyclization provide the corresponding tetrahydrofuran (Scheme 81).
38
J.D. Rainier
where they coupled an asymmetric Horner–Wadsworth–Emmons (HWE) reaction
with a Pd-catalyzed ring closure to generate cis- and trans-tetrahydrofuran derivatives (Schemes 76 and 77) [82]. From meso-dialdehyde 289, asymmetric HWE
gave E-alkene isomer 291 with high levels of diastereoselectivity. Aldehyde
reduction was followed by pivaloyl migration to afford cyclization precursor
292 in 63 % yield. Pd-catalyzed π-allyl formation and cyclization proceeded
with overall retention of stereochemistry to give 2,5-cis-tetrahydrofuran 293 in
76 % yield.
2,5-trans-Tetrahydrofurans were generated by Vares and Rein through the use of
the corresponding Z-olefin in the Pd-catalyzed cyclization. Asymmetric HWE using
trifluoroethylphosphonate ester 294 gave Z-olefin 295. Reduction of the remaining
aldehyde gave a 1.3:1 mixture of secondary alcohol 296 and the corresponding
primary alcohol. After separation, Pd-catalyzed cyclization resulted in the generation
of 2,5-trans-tetrahydrofuran 297 as the E-olefin isomer.
Enders and coworkers have observed high levels of enantioselectivity from
organocatalytic tandem Michael additions (Scheme 78). Their approach to tetrahydrofurans involved an initial nitrodiene-aldehyde condensation followed by an
intramolecular oxy-Michael addition [83]. As illustrated, the sequence gave 301 in
high diastereo- and enantioselectivity.
9 Miscellaneous Approaches to Tetrahydrofurans
Yamazaki and coworkers have described formal [3+2]-cycloadditions of ethene
tricarboxylates with substituted propargyl alcohols to give methylene tetrahydrofurans (Scheme 79) [84]. Interesting was that the E/Z selectivity of the reaction
depended upon the Lewis acid that was used. Z-Alkene isomers 304 were obtained
in moderate to high yields when triply activated alkene 302 was treated
with propargyl alcohol 303 in the presence of ZnBr 2 , InCl 3 , FeCl 3 , or AlCl 3 salts.
The corresponding E-isomer 308 was obtained when SnCl 4 was used. The authors
speculate that protonation in the SnCl 4 reaction occurs from allenyl species 309
where tin is coordinated to oxygen. Protonation in the Zn-, In-, Fe-, and
Al-catalyzed reactions is thought to occur from the Z-vinyl species 305.
Xi and coworkers have discovered that zirconacyclopentadienes can be used to
generate tetrahydrofurans when they are reacted with aldehydes [85]. The transformation requires the presence of CuCl and two equivalents of aldehyde (Scheme 80).
To explain the process, Xi et al. have proposed a mechanism where zirconacycle
312 reacts with the first equivalent of aldehyde to give 313. Transmetallation with
CuCl and reaction with the second equivalent of aldehyde provides cyclization
precursor 315. Acidic workup and cyclization provide the corresponding tetrahydrofuran (Scheme 81).
38
J.D. Rainier