Rhodium‐Catalyzed Diastereoselective Cyclization of Allenyl‐Sulfonylcarbamates: A Stereodivergent Approach to 1,3‐Aminoalcohol Derivatives

Abstract

A diastereoselective and stereodivergent rhodium-catalyzed intramolecular coupling of sulfonylcarbamates with terminal allenes is described and it provides selective access to 1,3-aminoalcohol derivatives, scaffolds found in bioactive compounds. The reaction is compatible with a large range of different functional groups, thus furnishing products with high diastereoselectivities and yields. Moreover, multigram scale reactions, as well as the application of suitable product transformations were demonstrated.

Rhodium‐Catalyzed Asymmetric Intramolecular Hydroamination of Allenes

“…[6] More recently,T oste,W idenhoefer and Liu utilized chiral Au Icomplexes and chiral Brønstedt acids for the asymmetric addition of amides and amines to internal allenes.U nfortunately,t hese reactions are limited to rather special substrate classes. [7,8] Throughout the last years,w er eported on as eries of rhodium-catalyzed chemo-, regio-, and enantioselective coupling reactions involving allenes [9,10] and alkynes [11] with various pronucleophiles,t hus establishing an atom efficient alternative to the classic allylic substitution. Especially in light of our previously reported diastereoselective addition of tosylated carbamates [10a] and tosylated amides, [10e] we envisioned that as uitable chiral catalyst might be able to realize an intramolecular,e nantioselective hydroamination of alkynes or allenes (Scheme 2).…”

Rhodium‐Catalyzed Asymmetric Intramolecular Hydroamination of Allenes

“…[1] Fort his reason, several asymmetric methods,l ike allylic substitution, [2] allylic oxidation, [3] and nucleophilic substitution/addition [4] have been disclosed for the preparation of these branched, a-chiral N-heterocyclic compounds.H owever,t hese approaches come along with limitations with regard to the requirement of stoichiometric amounts of aleaving group or an oxidant, thus rendering these syntheses economically unattractive.T hus,amore atom efficient [5] pathway involving at ransition metal catalyzed, intramolecular hydroamination/cyclization of C À Cm ultiple bonds is of greater interest. [7,8] Throughout the last years,w er eported on as eries of rhodium-catalyzed chemo-, regio-, and enantioselective coupling reactions involving allenes [9,10] and alkynes [11] with various pronucleophiles,t hus establishing an atom efficient alternative to the classic allylic substitution. [6] More recently,T oste,W idenhoefer and Liu utilized chiral Au Icomplexes and chiral Brønstedt acids for the asymmetric addition of amides and amines to internal allenes.U nfortunately,t hese reactions are limited to rather special substrate classes.…”

Rhodium‐Catalyzed Asymmetric N−H Functionalization of Quinazolinones with Allenes and Allylic Carbonates: The First Enantioselective Formal Total Synthesis of (−)‐Chaetominine

“…Recently,o ur group developed ar ange of rhodium-catalyzed atom-economic couplings between diverse pronucleophiles with allenes and alkynesi nahighly regio-and stereoselective manner to access branched allylic products. [7,8] In light of these previousresults, we envisioned that quinazolinones might be a suitable pronucleophiles to couple with allenes and allylic carbonates under appropriate catalytic system.H erein, we report an unprecedented rhodium-catalyzed asymmetric NÀHf unctionalization of quinazolinones with readily available unactivated terminal allenesa nd racemica llylic carbonates to afford chiral N-allylated quinazolinones, and its application in the first enantioselectivef ormal total synthesis of (À)-chaetominine. Initial reactivity assays for the optimization process utilized quinazolinone 1a and unactivated aliphatic terminal allene 2a as model substrates for the couplingr eaction.…”