Recent Advances in Asymmetric Hydrogenation of Tetrasubstituted Olefins

Abstract

The asymmetric hydrogenation of tetrasubstituted olefins provides direct access to very useful biological molecules and intermediates. The development of the technology has been slow, due in part to the synthetic challenges involved in developing chiral catalysts for a successful asymmetric induction. We briefly recount the breakthroughs in functionalized and unfunctionalized tetrasubstituted olefins, from the reports of Zhou and Buchwald for functionalized and unfunctionalized substrates, respectively, to the advent of chiral phosphoramidite ligands. The main emphasis of this Perspective lies in bringing into focus the complexity and challenges of inducing an asymmetric reduction for these substrates, which includes a brief discussion of the mechanism, the latest developed chiral catalysts, and the enormous scientific opportunities that still exist in developing "go to" catalyst systems for the various substrate types.

Heterolysis of Dihydrogen by Nucleophilic Calcium Alkyls

“…In particular,N BO analysis identifies as trong second order interaction between the filled amethylene sp 3 orbital of the n-hexyl chain and the s*o rbital of the H 2 molecule,signifying that the H À Hbond is broken by what is effectively the nucleophilic displacement of hydride by the organic substituent.Thecatalytichydrogenationofalkenesandalkynesbymidto late transition metal complexes has been developed to ahigh degree of sophistication and is typically predicated on the cooperative binding and activation of both unsaturated hydrocarbons and H 2 at ar edox-active metal center. [1][2][3][4][5][6][7][8][9] Albeit less well developed, similar catalysis was achieved by group 3and organolanthanide complexes more than aquarter of ac entury ago. [10][11][12][13][14] In these latter cases,ad 0 electron configuration mitigates against redox-based reactivity and turnover is derived from alkene insertion into ap olarised metal-hydrogen bond to form an alkyl intermediate,which is itself reactive toward H 2 through s-bond metathesis to release the hydrocarbon and regenerate the active hydride catalyst.…”

Heterolysis of Dihydrogen by Nucleophilic Calcium Alkyls

“…An atmosphere of dihydrogen (2 bar) was added to aC 6 D 6 solution of the calcium n-hexyl derivative (9). Immediate analysis of the resultant 1 HNMR spectrum confirmed that the solution comprised primarily am ixture of unreacted 9 (d = 4.69 ppm) and hydrogen (d = 4.46 ppm).…”

“…[1][2][3][4][5][6][7][8][9] Albeit less well developed, similar catalysis was achieved by group 3and organolanthanide complexes more than aquarter of ac entury ago. The reactions are deduced to take place with the retention of the dimeric structures of the calcium hydrido-alkyl and alkyl intermediates via aw ell-defined sequence of CaÀH/ C = Ci nsertion and Ca À Ch ydrogenation events.T his latter deduction is strongly supported by DFT calculations (B3PW91) performed on the 1-hexene/H 2 system, which also indicates that the hydrogenation transition states display features whichd iscriminate them from ac lassical s-bond metathesis mechanism.…”

“…[1][2][3][4][5][6][7][8][9] Albeit less well developed, similar catalysis was achieved by group 3and organolanthanide complexes more than aquarter of ac entury ago. [1][2][3][4][5][6][7][8][9] Albeit less well developed, similar catalysis was achieved by group 3and organolanthanide complexes more than aquarter of ac entury ago.…”

“…Further insight into this proposed mechanism was provided by density functional theory (DFT) calculations carried out with the same computational approach (B3PW91, see SI) previously used to describe the stepwise formation of the dicalcium di-n-hexyl derivative (9), through the reaction of compound 3 with 1-hexene. [23] Thef irst 1-hexene insertion with compound 3 was described in our previous report and the associated barrier yielding the dicalcium n-hexyl-hydride complex C (6)i s2 0.1 kcal mol À1 .F rom C (6), either hydrogenation by H 2 (left part of Figure 2) or further 1-hexene insertion (right part of Figure 2) was considered computationally.I ts hould first be noted that both reactions occur on the bimetallic species as the hydride dimer dissociation was computed to be endothermic by 40.4 kcal mol À1 ( Figure S20 in the Supporting Information).…”