Organic Letters
Letter
substrate, leading to products 3ag and 3ah with high E-
selectivity. Further investigation showed that the reaction was
sluggish with messy products (3ai) when 2-nitro-2-phenyl-
ethan-1-ol was used as the substrate. Furthermore, this
sequential reaction was scaled up to 1.3 to 2.0 mmol for
practical applications, generating 3e and 3ah in 68% and 55%
yield, respectively.
To further investigate the reaction pathway, we reinvesti-
gated the reaction of 1a and 2v under the optimal conditions
(Scheme 4a). Because of the base reactions, a certain amount
sequently, intermediate II from path a was achieved after
Brook rearrangement. Due to the restricted rotation with steric
hindrance depicted in the Newman projection model II, anti-
periplanar elimination is unfavored, generating minor product
4. In contrast, the preferred conformation IV obtained from
path b with the NO2 group at the anti-periplanar position is
favored for elimination, giving the Z-selectivity product Z-3
when the R substituent is hydrogen. Interestingly, the retro-
Henry process from V to VI occurred when the R substituent
was not hydrogen, generating the E-selective product E-3 as
the major product.
In summary, we have developed a novel hydrogen-bond-
assisted controlled sequential reaction of silyl glyoxylates. This
method enables efficient geometric synthesis of trisubstituted
silyl enol ethers with high selectivity. With the assistance of
hydrogen bonds, the stereochemical outcome for both E- and
Z-isomers depended on the structure of 2-nitroethanol and its
derivatives. Further studies of new reactions of silyl glyoxylates
are currently underway.
Scheme 4. Control Experiments and Proposed Mechanism
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
Full experimental details and characterization data for all
AUTHOR INFORMATION
Corresponding Authors
■
Lei Wang − Department of Chemistry, Key Laboratory of
Green and Precise Synthetic Chemistry, Ministry of
Education, Huaibei Normal University, Huaibei, Anhui
235000, P.R. China; State Key Laboratory of Organometallic
Chemistry, Shanghai Institute of Organic Chemistry,
Shanghai 200032, P.R. China; Advanced Research Institute
and Department of Chemistry, Taizhou University, Taizhou,
Man-Yi Han − Department of Chemistry, Key Laboratory of
Green and Precise Synthetic Chemistry, Ministry of
Education, Huaibei Normal University, Huaibei, Anhui
of the hydrolysis product benzyl alcohol was obtained with a
36% yield in this transformation. However, no tetrasubstituted
silyl enol ether (4av) was observed, and similar results for the
preparationof 3c′ are also shown in Scheme 3a.
Considering that steric effects, such as the large size of the
phenethyl substituent form 2v and benzyl substituent form 2h,
have an unfavorable effect on elimination, the reaction of 1a
and 2- nitro ethanol 2p with a small methyl group was
conducted under the optimal conditions. Satisfyingly, the
tetrasubstituted silyl enol ether product 4ap was obtained via
Henry reaction/Brook rearrangement/elimination processes.
Moreover, a certain amount of the hydrolysis product benzyl
alcohol was also obtained with a 31% yield. The experimental
data and these control experiments indicated that the
competitive relationship between the direct elimination
process and retro-Henry reaction/elimination process and
the product structure depend on the size of the substituent on
the 2-nitroethanol derivatives. Moreover, compared to the
hydrolysis processes of benzyl-based ester, the hydrolysis of
tertiary butyl ester was inhibited due to its large steric
hindrance and leaving group ability. Accordingly, the reaction
mechanism proceeding via a competitive pathway was
proposed. As shown in Scheme 4b, after the nucleophilic
addition of nitroethanol (2) to silyl glyoxylate (1) under PTC
conditions, intermediates I and III were obtained. To observe
the elimination processes more easily, the chair forms I and III
were proposed, and the nitro group (NO2) was fixed at the
axial bond. In these transformations, the alkoxide could be
stabilized by hydrogen bonds from the OH group. Sub-
Authors
Chen Zhu − Department of Chemistry, Key Laboratory of
Green and Precise Synthetic Chemistry, Ministry of
Education, Huaibei Normal University, Huaibei, Anhui
235000, P.R. China
Xiu-Xia Liang − Department of Chemistry, Key Laboratory of
Green and Precise Synthetic Chemistry, Ministry of
Education, Huaibei Normal University, Huaibei, Anhui
235000, P.R. China
Bin Guan − Department of Chemistry, Key Laboratory of
Green and Precise Synthetic Chemistry, Ministry of
Education, Huaibei Normal University, Huaibei, Anhui
235000, P.R. China
Pinhua Li − Department of Chemistry, Key Laboratory of
Green and Precise Synthetic Chemistry, Ministry of
Education, Huaibei Normal University, Huaibei, Anhui
235000, P.R. China; State Key Laboratory of Organometallic
Chemistry, Shanghai Institute of Organic Chemistry,
D
Org. Lett. XXXX, XXX, XXX−XXX