Engaging Aldehydes in CuH‐Catalyzed Reductive Coupling Reactions: Stereoselective Allylation with Unactivated 1,3‐Diene Pronucleophiles

Abstract

Recently,C uH-catalyzed reductive coupling processes involving carbonyl compounds and imines have become attractive alternatives to traditional methods for stereoselective addition because of their ability to use readily accessible and stable olefins as surrogates for organometallic nucleophiles. However,t he inability to use aldehydes,w hich usually reduce too rapidly in the presence of copper hydride complexes to be viable substrates,h as been am ajor limitation. Shownh ere is that by exploiting relative concentration effects through kinetic control, this intrinsic reactivity can be inverted and the reductive coupling of 1,3-dienes with aldehydes achieved. Using this method, both aromatic and aliphatic aldehydes can be transformed into synthetically valuable homoallylic alcohols with high levels of diastereo-and enantioselectivities,and in the presence of many useful functional groups.Furthermore, using ac ombination of theoretical (DFT) and experimental methods,i mportant mechanistic features of this reaction related to stereo-and chemoselectivities were uncovered.

Copper-Catalyzed Highly Enantioselective 1,4-Protoboration of Terminal 1,3-Dienes

“…[104][105][106][107] In addition, both compound 5a and 6a could originate from this Cu-complex (7a). [106][107][108][109][110][111] Under the optimized reaction conditions, the intermediate 7a could convert into product 5a via a six-membered type transition state. [108][109][110][111][112] Moreover, 7a could be quenched by AcOH to afford compound 6a without forming the desired product 5a (Table 1, entry 6).…”

“…[106][107][108][109][110][111] Under the optimized reaction conditions, the intermediate 7a could convert into product 5a via a six-membered type transition state. [108][109][110][111][112] Moreover, 7a could be quenched by AcOH to afford compound 6a without forming the desired product 5a (Table 1, entry 6). 106,107 Furthermore, the consumption of 1a could induce the low concentration of 7a, which causes the signal of 6a to decrease in the late stage of the reaction process (Scheme 3 and Figure 2, 6a).…”

“…As the key intermediate, 7a affords the desired product 5a via protonation. [108][109][110][111][112] The feasibility of 1 mmol scale reaction was established under standard reaction conditions. The above reaction afforded desired product 5a with 68% yield and 97% ee (Figure 3, (1), and Supporting Information).…”