Asymmetric Nitrocyclopropanation of α‐Substituted α,β‐Enals Catalyzed by Diphenylprolinol Silyl Ether for the Construction of All‐Carbon Quaternary ­Stereogenic Centers

Abstract

The diphenylprolinol silyl ether mediated asymmetric nitrocyclopropanation of α‐substituted α,β‐unsaturated aldehydes with bromonitromethane, followed by base‐promoted isomerization was found to afford trans‐nitrocyclopropanecarbaldehydes with all‐carbon quaternary stereogenic centers with excellent diastereo‐ and enantioselectivities. DFT calculations indicated that the s‐trans conformer of the iminium ion intermediate is more stable than the s‐cis conformer. In addition, nucleophilic attack of the bromonitromethane anion to the iminium ion intermediate was calculated to occur preferentially from the opposite side of the bulky substituents of the pyrrolidine iminium intermediate.

Asymmetric Diels–Alder Reaction of α‐Substituted and β,β‐Disubstituted α,β‐Enals via Diarylprolinol Silyl Ether for the Construction of All‐Carbon Quaternary Stereocenters

“…[21] The resultant six geometries within 12 kcal mol À1 from the most stable were optimized by the DFT/B3LYP/DGDZVP level of theory using Gaussian 09. The overall agreement in these spectra unambiguously confirmed the absolutec onfiguration of 13 as 1R,2R,3R,6S,7R,9S.T hus, the absolute configurationo f This result led us to propose that the reaction of b,b-disubstituted a,b-unsaturated aldehyde proceeds via as imilar transition state of b-mono-substituted a,b-unsaturateda ldehyde, shown in Figure 2B,i nw hich the reactionp roceeds via an strans iminium ioni ntermediate, [15] and cyclopentadiener eacts from the opposite side of the bulky diphenylsiloxymethyl substituentthrough the exo mode. The overall agreement in these spectra unambiguously confirmed the absolutec onfiguration of 13 as 1R,2R,3R,6S,7R,9S.T hus, the absolute configurationo f This result led us to propose that the reaction of b,b-disubstituted a,b-unsaturated aldehyde proceeds via as imilar transition state of b-mono-substituted a,b-unsaturateda ldehyde, shown in Figure 2B,i nw hich the reactionp roceeds via an strans iminium ioni ntermediate, [15] and cyclopentadiener eacts from the opposite side of the bulky diphenylsiloxymethyl substituentthrough the exo mode.…”

“…[22] The IR and VCD spectra of the obtained five conformers within 1.6 kcal mol À1 from the most stable conformer were calculated at the same level of theory,a nd the final spectra were simulated based on the Boltzmann population average of each conformer.F igure 3s hows the experimental and theoretical spectra of 13.M ost of the peaks seen in the observed VCD showed ao ne-to-one correspondence witht hose in the calculated spectra,i ncluding their sign. The overall agreement in these spectra unambiguously confirmed the absolutec onfiguration of 13 as 1R,2R,3R,6S,7R,9S.T hus, the absolute configurationo f This result led us to propose that the reaction of b,b-disubstituted a,b-unsaturated aldehyde proceeds via as imilar transition state of b-mono-substituted a,b-unsaturateda ldehyde, shown in Figure 2B,i nw hich the reactionp roceeds via an strans iminium ioni ntermediate, [15] and cyclopentadiener eacts from the opposite side of the bulky diphenylsiloxymethyl substituentthrough the exo mode. [4k, 7e, g, 23]…”

“…At ransition-state model is indicated in Figure2A, in which the reaction proceeds via an s-trans iminium ion intermediate, [15] and cyclopentadiene reacts from the opposite side of the bulky diphenylsiloxymethyl substituent throught he exo mode. [19] In the case of b,b-disubstituted a,b-unsaturated aldehyde, we determined the relative anda bsolute configurations as follows (Scheme 1): Diels-Alder products 11-exo and 11-endo of 3-ethoxycarbonyl-2-butenal andc yclopentadiene (Table 4, entry 1) were reduced with NaBH 4 to afford am ixture of alcohols 12-exo and 12-endo,w hich was treated with I 2 .F rom the exo-isomer,i odo-lactonization proceeded to provide iodo lactone 13 in 60 %y ield, whereas iodo-etherification proceeded from the endo-isomer to afford iodo ether 14 in 20 %y ield.…”

“…[13] However,w er eportedt he asymmetric epoxidationo fa-substituted acrolein by using diphenylprolinol silyl ether for the constructiono ft etrasubstituted tertiary centers. [15] These results prompted us to investigate the asymmetric Diels-Alder reactiono fa-substituted acrolein with our catalyst. [15] These results prompted us to investigate the asymmetric Diels-Alder reactiono fa-substituted acrolein with our catalyst.…”

“…[14] We also developed nitrocyclopropanationo fa-substituted acroleinc atalyzed by the same catalystf or the construction of all-carbon quaternary stereogenic centers. [15] These results prompted us to investigate the asymmetric Diels-Alder reactiono fa-substituted acrolein with our catalyst. We further investigated the Diels-Alder reaction of b,b-disubstituteda crolein.…”