Rhodium-catalyzed enantioselective desymmetrization of bicyclic hydrazines with alkynylboronic esters

Abstract

The first successful asymmetric transfer of rhodium-alkynyl species to symmetrical strained alkenes has been realized starting from bicyclic hydrazines and alkynylboronic esters.

Enantioselective Rhodium‐Catalyzed Nucleophilic Allylation of Cyclic Imines with Allylboron Reagents

“…To date, this field has been dominated by the enantioselective addition of arylboron reagents, [1] though there have also been reports of additions of alkenylboron [2] and alkynylboron reagents. [3,4,5] Notably absent are the corresponding rhodium-catalyzed enantioselective additions of allylboron reagents, [6,7] despite the widespread importance of nucleophilic allylations in synthesis. [ 8,9 ] In this communication, we describe the first enantioselective rhodium-catalyzed additions of allylboron reagents to -electrophiles in the form of asymmetric allylation of cyclic imines using potassium allyltrifluoroborates.…”

An Enantioselective CpxRh(III)‐Catalyzed C−H Functionalization/Ring‐Opening Route to Chiral Cyclopentenylamines

“…Functionalized chiral cyclopentenylamines are important structural motifs of natural products and pharmaceutically relevant molecules (Figure 1) [11] and have attracted significant attention from the synthetic community. [12] Fori nstance,t he ring-opening desymmetrization of diazabicycles with suitable preformed organometallic species emerged as ap owerful approach to vicinal aryl cyclopentylamines.T he groups of Lautens [13] and Pineschi [14] reported asymmetric Rh I -catalyzed methods to access this structural motif from diazabicycles and aryl boronic acids (Scheme 1). Inspired by the cyclopentenylamine syntheses [15] of the groups of Cui [15a] and Radhakrishnan, [15b,d] we envisioned ac hiral Cp x Rh III -catalyzed directed CÀHactivation-addition sequence followed by b-heteroatom elimination [15] to forge the two stereogenic centers of the targeted chiral cyclopentenylamine products.…”

Asymmetric Conjugate Alkynylation of Cyclic α,β‐Unsaturated Carbonyl Compounds with a Chiral Diene Rhodium Catalyst

“…[3] We have previously reported rhodium-catalyzed asymmetric addition of (triisopropylsilyl)acetylenet oa,b-unsaturated ketones, [5] where the main side-reaction forming the acetylene dimer [10] was suppressed by use of ab ulky chiral bis(phosphine) ligand, DTBM-segphos (Scheme 1a). Use of alkynylsilanol as an alkynylating reagent and appropriate chiral ligands improved the yield and enantioselectivity for both acyclic and cyclic enones [7,8] (Scheme 1b), but it still has drawbacks in that an excess amount of the alkynylating reagent must be used for ah igh chemical yield and, more importantly,t he substrate scope is not broad. Use of alkynylsilanol as an alkynylating reagent and appropriate chiral ligands improved the yield and enantioselectivity for both acyclic and cyclic enones [7,8] (Scheme 1b), but it still has drawbacks in that an excess amount of the alkynylating reagent must be used for ah igh chemical yield and, more importantly,t he substrate scope is not broad.…”

“…[1] While an umber of efficient reaction systems have been reported on the asymmetric conjugate addition of sp 3 -a nd sp 2 -carbon nucleophiles by use of chiral metal catalysts and organocatalysts, [2] thed evelopment has been slow on the asymmetric introduction of sp-carbon atoms (alkynyl groups). Thecatalytic asymmetric conjugate alkynylation has been reported with nickel, [3] copper, [4] rhodium, [5][6][7][8] and other metal [9] complexes as catalysts.A lthough high yields and high enantioselectivities have been reported for some of acyclic a,b-unsaturated carbonyl compounds,t here have been only af ew reports on successful asymmetric alkynylation of cyclic substrates,t ypically 2-cyclohexenone and 2-cyclopentenone.O ne of them is the nickel-catalyzed addition of alkynylaluminum reagents reported by Corey and co-workers,w herein 3-alkynylcyclohexanones were obtained with 85-90 % ee. [3] We have previously reported rhodium-catalyzed asymmetric addition of (triisopropylsilyl)acetylenet oa,b-unsaturated ketones, [5] where the main side-reaction forming the acetylene dimer [10] was suppressed by use of ab ulky chiral bis(phosphine) ligand, DTBM-segphos (Scheme 1a).…”

“…The rhodium catalyst system consisting of DTBM-segphos and (triisopropylsilyl)acetylenel ed to high yields and high enantioselectivities for acyclic a,b-unsaturated ketones,t ypically 1-phenylbut-2-en-1-one and some other reactive substrates, [6] but it is not applicable to less reactive cyclic enones because the alkynylrhodium intermediate with the very bulky ligand, DTBM-segphos,i sn ot reactive toward the cyclic enones (Scheme 1a). Use of alkynylsilanol as an alkynylating reagent and appropriate chiral ligands improved the yield and enantioselectivity for both acyclic and cyclic enones [7,8] (Scheme 1b), but it still has drawbacks in that an excess amount of the alkynylating reagent must be used for ah igh chemical yield and, more importantly,t he substrate scope is not broad. In this context, we have looked for better reaction systems for the asymmetric conjugate alkynylation with ab roader substrate scope.H erein we report our recent findings that the asymmetric conjugate alkynylation takes place in high yields with high enantioselectivity by use of an alkynyl(diphenyl)methanol as an alkynylating reagent and an ew chiral diene ligand bearing ferrocenyl groups (Scheme 1c).…”