Highly Enantio‐ and s‐trans CC Bond Selective Catalytic Hydrogenation of Cyclic Enones: Alternative Synthesis of (−)‐Menthol

Abstract

A highly enantioselective catalytic hydrogenation of cyclic enones was achieved by using the combination of a cationic Rh(I) complex, (S)-5,5'-bis{di(3,5-di-tert-butyl-4-methoxyphenylphosphino)}-4,4'-bi-1,3-benzodioxole (DTBM-SEGPHOS), and (CH2CH2PPh3Br)2. The presence of an s-cis C=C bond isopropylidene moiety on the cyclic enone influenced the enantioselectivity of the hydrogenation. Thus, the hydrogenation of 3-alkyl-6-isopropylidene-2-cyclohexen-1-one, which contains both s-cis and s-trans enones, proceeded in excellent enantioselectivity (up to 98 % ee). To obtain high enantio- and s-trans selectivities, the addition of a halogen source to the cationic Rh complex was the essential step. With the key step of the s-trans selective asymmetric hydrogenation of piperitenone, we demonstrated a new synthetic method for optically pure (-)-menthol via three atom-economical hydrogenations. Moreover, we found that the complete s-trans and s-cis C=C bond selective reactions were also realized by the proper choice of both the chiral ligands and halides.

Unprecedented Selectivity via Electronic Substrate Recognition in the 1,4‐Addition to Cyclic Olefins Using a Chiral Disulfoxide Rhodium Catalyst

“…In these cases, the relative orientation of the tolyl groups hinders formation of the dimer, a phenomenon that was observed earlier for atropisomeric diphosphine ligands incorporating bulky aromatic groups on the phosphorous atoms. [10] To unambiguously assign the stereochemistry of the present system and to better understand the binding situation of sulfoxides, crystal structure analyses of one of the ligands (1 a) and its corresponding rhodium complex 2 a were performed ( Figure 1). For comparison, we also synthesized and crystallized the analogous diphosphine complex [({(S)-biphemp}RhCl) 2 ] (3, see the Supporting Information).…”

Highly Chemo‐ and Enantioselective Hydrogenation of Linear α,β‐Unsaturated Ketones

“…[14] The most recent developments stem from Mashima and co-workers, who used a cationic Rh I /DTBM-SegPhos/(CH 2 CH 2 PPh 3 Br) 2 catalyst system to hydrogenate endo-cyclic enones providing products with up to 98 % ee. [15] Heterogeneous hydrogenations of exo-cyclic enones have also been investigated, [16] but only moderate enantioselectivities were achieved.Recently, we reported the synthesis of sulfoximine-derived P,N-ligands and their applications in iridium-catalyzed asymmetric hydrogenation reactions. [17,18] As part of our continued interest in the area and with the goal to explore the general reactivity pattern of this catalyst family (see below, complexes 1 and 2), we focused our efforts now on the hydrogenation of a,b-unsaturated ketones.We began the study using linear b,b-disubstituted 1,3-diphenyl-2-butenone [(E)-4 a] as model substrate and iridium [a] Dr.COMMUNICATION complex 1 a as catalyst (1 mol %).…”

“…[14] The most recent developments stem from Mashima and co-workers, who used a cationic Rh I /DTBM-SegPhos/(CH 2 CH 2 PPh 3 Br) 2 catalyst system to hydrogenate endo-cyclic enones providing products with up to 98 % ee. [15] Heterogeneous hydrogenations of exo-cyclic enones have also been investigated, [16] but only moderate enantioselectivities were achieved.…”

“…Thus, methyl substituted (E)-4 a was hydrogenated with 1 c as catalyst to give a product with 81 % ee ( Table 2, For the hydrogenation of enone (Z)-4 c, which differed from (E)-4 c by its altered olefin geometry, both conversion and enantioselectivity were slightly lower (compared with the analogous reaction of its diastereomeric counterpart). The absolute configuration of the product (ketone 5 c) was reversed (entries [14][15][16], which indicated that the catalyst approached the olefin from the same face. Consequently, the ratio of the (Z)-and (E)-isomers will greatly affect the enantioselectivity of the product.…”

Enantioselective Hydrogenation of Enones with a Hydroformylation Catalyst

“…[9,10] We focus on the chemo-and enantioselective hydrogenation of enones to saturated, chiral ketones. This class of substrates is not a preferred class of substrates for Rh-catalyzed enantioselective hydrogenation and the chiral products have since recently [11] only been readily accessible via reductions employing high molecular mass hydride donors, such as silanes, borohydrides or dihydropyridines. [12,13] Initially, we screened various rhodium complexes as suitable precursors for the hydrogenation of isophorone, making use of the readily available chiral ligand Chiraphos (Table 1).…”