N-Thiophosphoryl imines: convenient substrates in the aza-Henry reaction

Enantioselective copper‐aminopyridine‐catalyzed aza‐Henry reaction with chelating N‐(2‐pyridyl)sulfonyl imines

“…Most significantly, up to two new stereogenic centers can be formed, both attached to two different nitrogen functional groups. As a result, much attention has been paid to the catalytic asymmetric version of this reaction over the past several years by either using metal‐based procedures or organocatalysis . One of the difficulties that arises when carrying out nucleophilic addition reactions to imines is their lower electrophilicity compared with the carbonyl group.…”

“…However, a common drawback associated with the use of this type of imines is that precautions have to be taken during preparation, handling, and storage because of their substantial hydrolytic lability. N ‐phosphinoyl imines have been seldom used because of their poor stability and relatively low reactivity, although the phosphinoyl moiety can be easily removed by acidic hydrolysis. Similarly, there are few reports on the enantioselective aza‐Henry reaction of N ‐sulfonyl protected imines, which are usually bench‐stable solids and can be easily prepared.…”

Iron-Catalyzed Asymmetric Nitro-Mannich Reaction

“…However, all of the above-mentioned examples require a high catalyst (20 or even 30 mol %) and chiral ligand (20−45%) loading, while the substrate scope was limited with regards to one or both of the reaction partners. The alternative organocatalytic asymmetric nitro-Mannich reactions have been also reported by Johnston, 6 Takemoto, 7 Zhou, 8 and Jacobsen 9 featuring, however, some important restrictions regarding the substrate scope.…”

“…J = 6 8. Hz,3H major ), 1.50 (d, J = 6.7 Hz, 3H minor );13 C NMR (151 MHz, CDCl 3 ) δ 159.7 (d, J = 8.7 Hz), 132.7 (d, J = 9.8 Hz), 132.6, 132.5−132.1 (m), 131.9−131.8 (m), 131.5, 131.4, 131.0, 130.6 (d, J = 2.1 Hz), 129.5 (d, J = 4.4 Hz), 128.8−128.5 (m), 128.2, 128.0, 114.5, 114.3, 88.5 (d, J = 5.9 Hz), 87.8, 58.1, 57.9, 55.4 (d, J = 6.4 Hz), 17.2 (d, J = 3.2 Hz), 15.8 (d, J = 3.0 Hz).…”

Stereoselective Total Synthesis of KAE609 via Direct Catalytic Asymmetric Alkynylation to Ketimine

“…The synthesis of KAE609 was initiated by direct catalytic asymmetric alkynylation of functionalized terminal alkyne 3 to N -(diphenyl­thiophos­phinoyl­(thioDpp))­ketimine 4a derived from 5-chloroisatin (Table ). , Based on our previous communication documenting the alkynylation of N -thioDpp-ketimines derived from aryl alkyl ketones (e.g., acetophenones), we applied a catalyst comprising mesitylcopper/( S , S )-Ph-BPE for the alkynylation using terminal alkyne 3a with the requisite halogen substituents and a free amino group (entry 1). In contrast to the reaction using N -thioDpp-ketimines derived from normal ketones, 4a exhibited much higher reactivity and the reaction proceeded even at −78 °C, affording 5a in 79% yield with 73% ee.…”