Merging Copper Catalysis with Nitro Allyl and Allyl Sulfone Derivatives: Practical, Straightforward, and Scalable Synthesis of Diversely Functionalized Allyl Boranes

Abstract

We report here the first example of a copper-catalyzed transformation involving nitro allyl derivatives. This borylation reaction, which exploits the high versatility of the aforementioned precursor, tolerates a variety of functional groups and allows practical, scalable, and highly straightforward access to diversely substituted allylboronic esters in high yields. The method was also extended to allyl sulfones, which provides a very complementary approach, offering additional structural diversity along with improved stereoselectivities. This new reactivity was further exploited to synthesize γ-fluoroallyl boronic esters as well as various synthetically useful building blocks through key post-functionalizations. Both the reaction mechanism and the chemoselectivity were rationalized experimentally and through DFT calculations.

Figure 1

Strategies for the synthesis of allylboronic esters.

Figure 2

Substrate scope. (a) Reaction run using 2 mol % of CuCN. (b) Determined by 1H NMR on the crude reaction mixture. (c) Reaction run over a period of 24 h.

Figure 3

Free energy profile of the cupro-borylation of 3-methyl-3-nitrobutene followed by the β-nitrite elimination leading to the corresponding allylborane. Both anti and syn pathways are represented for each chemical step. Vertical arrows in magenta indicate a conformational equilibrium. The 3D molecular structures of Int-anti and Int-syn are shown as insets (for the sake of clarity, all H atoms are hidden except those close to the reaction center). The structures of the end points of the reaction (in black here) are shown in Figure S1 in the Supporting Information. The remaining molecular structures for the cupro-borylation and β-nitrite elimination steps are shown in Figure S2 in the Supporting Information.

Figure 4

Synthesis of γ-fluoroallyl boronic esters. (a) Determined by ¹H NMR on the crude reaction mixture.

Figure 5

Comparison of the β-elimination pathways with the fluorine or nitro leaving groups, starting from the S intermediate. The 3D molecular structures of all TSs, adducts, and final products are shown in Figure S4 in the Supporting Information.

Figure 6

(A) Optimization of the reaction conditions for 1,2-disubstituted alkenes. (B) Extension to internal alkenes. (C) Redox compatibility test between diborane species and sodium nitrite (top). Redox compatibility test between ate complex and sodium nitrite (bottom). (D) Synthesis of δ-lactones via allylation and subsequent cyclization. (E) Derivatization of monofluoro allylboranes: allylation of p-chlorobenzaldehyde (top); synthesis of dienes through a Pd-catalyzed Suzuki/dehydrofluorination cascade (bottom). (F) Derivatization of tetrasubstituted allylboranes: oxidation to the corresponding allylic alcohol (top); synthesis of γ-lactones through an oxidation/lactonization cascade (center); and diastereoselective synthesis of δ-lactones via allylation and subsequent cyclization. (G) NCIplot of TSs associated with the elimination of methanol: strong stabilizing interactions are highlighted in blue, weak interactions are highlighted in green, and strong destabilizing interactions are highlighted in red. TS leading to the major compound with the two aryl rings in a cis conformation (left); TS leading to the formation of the minor compound with the two aryl rings in a trans conformation (right). (H) t-BuCHO/Sc(OTf)₃-mediated formal γ-oxidation/lactonization of 2j and 9 leading to γ-lactone 11 [PFA = paraformaldehyde].

Figure 7

Copper-catalyzed borylation of allyl sulfone derivatives. (a) Determined by ¹H NMR on the crude reaction mixture.