*2.2. Enantioselective Reduction of Tetrasubstituted Nitroalkenes (***3***)*

The use of Hantzsch esters as biomimetic reducing agents [17] has been reported in different organocatalytic reductions of nitroalkenes, but also ketoimines and ketoesters [18–20]. In addition, Hantzsch esters are easily synthetized, and their structure readily tuned in order to maximize the efficiency of enantioselective reactions [21].

The enantioselective reduction of the synthetized tetrasubstituted nitroalkenes (**3**) using Hantzsch esters as a reductive agent and a thiourea based chiral catalyst was investigated to obtain the corresponding functionalized nitroalkanes (**4**) (Scheme 3), in the presence of a few chiral bifunctional catalysts **A**–**D**, representative of different classes of the most popular organocatalysts for this transformation. The results are reported in Table 3.

**Scheme 3.** Organocatalytic reduction of tetrasubstituted nitroalkenes.

In general, compounds **4** were obtained in a 1:1 mixture of *syn/anti* products after 24 h of reaction time. Initial experiments were conducted using nitroalkane **3a** (Table 3, entries 1–8) as model substrate. The reactions performed in the presence of catalyst **A** starting from different mixtures of nitroalkene **3a** (Table 3, entries 1–3), demonstrate a different reactivity of the *E*–*Z* isomers of this compound, showing that one isomer reacted more quickly than the other one. This interesting discovery was confirmed when the reaction was performed with a pure fraction of the less reactive isomer (which was previously assigned as having a *Z* configuration) and no reaction was observed (Table 3, entry 1). Starting from differently enriched mixtures in the *E* isomer led to similar results (entries 2–3), leading to the chiral alkanes in up to 67% enantiomeric excess (entries 2–3). Attempts to increase the yield by operating at a higher temperature or to improve the enantioselectivity by running the reaction at a lower temperature did not lead to any significant results. The enantioselectivity of the reaction was measured by HPLC analysis of the pure samples on the chiral stationary phase, and two pairs of enantiomers, corresponding to *syn/anti* products, were found (see experimental section).


**Table 3.** Enantioselective reduction of tetrasubstituted nitroalkenes.

<sup>a</sup> Reaction was performed using a 4:96 *E*–*Z* mixture of the nitroalkene; <sup>b</sup> Reaction was performed using an 90:10 *E*–*Z* mixture of the nitroalkene; <sup>c</sup> Reaction was performed using a 70:30 *E*–*Z* mixture of the nitroalkene; <sup>d</sup> Yield was determined after purification with column chromatography; <sup>e</sup> Determined using chiral HPLC column Phenomenex-Lux-Cellulose 5, Hexane/IPA 98:2 for compound **4a** and Hexane/IPA 95:5 for compounds **4d**–**f**; n.d. = not determined.

When thiourea catalyst **B** was used (Table 3, entry 6), the corresponding nitroalkane **3a** was obtained with good yield, but the enantioselectivity observed was lower than with catalyst **A** (Table 3, entry 2), which was the best catalyst for this transformation. When the thiourea catalysts **C** and **D** were tested (Table 3, entries 7,8), the yields were drastically reduced, with a very low quantity of product obtained after purification. With the optimized conditions in hand, the enantioselective reduction of nitroalkenes **3d**–**f** (Table 3, entries 9–11) was carried out using Hanztsch ester and thiourea catalyst **A**. Compounds **4d**–**f** were obtained with good yields after purification, but generally low or modest enantioselectivities.
