Rhodium-Catalyzed Enantioselective Hydroamination of Alkynes with Indolines

Abstract

The hydroamination of internal alkynes via tandem rhodium-catalysis gives branched N-allylic indolines with high regio- and enantioselectivity. An acid-switch provides access to the linear isomer in preference to the branched isomer by an isomerization mechanism. Mechanistic studies suggest formation of an allene intermediate, which undergoes hydroamination to generate allylic amines instead of the enamine or imine products typically observed in alkyne hydroaminations.

Enantioselective and Regiodivergent Addition of Purines to Terminal Allenes: Synthesis of Abacavir

“…[11] Nevertheless,t he direct coupling of purines in ac hemo-, regio-and enantioselective manner is still underdeveloped. [12] Due to prior reports on the rhodium-catalyzed atomeconomic coupling of pronucleophiles to allenes and alkynes, [13,14] as an atom-economic alternative to the Tsujii-Tr ost allylation, we were encouraged to apply as imilar methodology towards more complex purine-type nucleophiles.D ue to tautomerism, several regioselectivity issues have to be taken into account. Linear and branched products as well as the corresponding N 9 /N 7 substituted products may arise during the hydroamination process (Scheme 1).…”

Transition‐Metal‐Catalyzed Regiodivergent and Stereoselective Access to Branched and Linear Allylated 4‐Pyridones

“…We recently reported on a series of addition reactions of pronucleophiles to allenes and alkynes leading to regio‐ and enantioselective C−O, C−S, C−N, and C−C bond formation that can be seen as atom‐economic alternatives to the transition‐metal‐catalyzed allylic substitution and allylic oxidation . We herein report the first rhodium‐ and palladium‐catalyzed regiodivergent and stereoselective addition of 4‐pyridones to terminal allenes, affording in a regiodivergent manner both chiral branched and linear E ‐allylated 4‐pyridones in high yields as well as regio‐ and stereoselectivities.…”

“…[4] The 4pyridone is knowna sa na mbident nucleophile existing in two tautomeric forms, the 4-pyridonea nd the 4-hydroxypyridine, which in the course of alkylation reactions can lead to mixtures of O-and N-alkylated products (Scheme 2). [5][6][7][8] We recently reported on as eries of addition reactions of pronucleophiles to allenesa nd alkynes leadingt or egio-and enantioselective CÀO, CÀS, CÀN, and CÀCb ond formation [9,10] that can be seen as atom-economic alternatives to the transition-metal-catalyzed allylic substitution [11] and allylic oxidation. [12] We herein report the first rhodium-and palladium-catalyzed regiodivergent and stereoselective addition of 4-pyridonest ot erminal allenes,a ffording in ar egiodivergent manner both chiral branched and linear E-allylated 4-pyridones in high yields as well as regio-a nd stereoselectivities.Our study commencedw ith 4-pyridone (1)a nd 3-phenylpropyl allene (2)a sm odel substrates( Ta ble 1) in the presence of 2.5 mol %[ Rh(COD)Cl] 2 (COD = 1,5-cyclooctadiene) and 5.0 mol % rac-BINAP [BINAP = 2,2'-bis(diphenylphosphino)-1,1'binaphtyl] in 1,2-dichloroethane (DCE) at 80 8C.…”

Iridium‐Catalyzed Enantioselective Intermolecular Indole C2‐Allylation

“…[3] Thea nalogous N1-allylation is relatively less well-explored, although there exist various innovative methods for this recently developed by the groups of Hartwig, [4] You, [5] Krische [6] and others. [7] To the best of our knowledge,there are no methods capable of directly allylating indole at the C2-position in an enantioselective,i ntermolecular fashion.…”