skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Explore Research Products in the PAR
It may take a few hours for recently added research products to appear in PAR search results.


Title: Cationic Bis(phosphine) Cobalt(I) Arene Complexes as Precatalysts for the Asymmetric Synthesis of Sitagliptin
The cobalt-catalyzed asymmetric hydrogenation of dehydro-sitagliptin was studied and applied to the synthesis of sitagliptin (Januvia®). Catalyst discovery efforts were accelerated by the application of a general method for the synthesis of cationic bis(phosphine) cobalt η6-arene complexes. One-electron oxidation of bis(phosphine) cobalt(II) dialkyl complexes in the presence of arenes furnished the corre-sponding, bench stable cobalt precatalysts, [(P-P)Co(η6-C6H6)][BArF4]. Asymmetric hydrogenation utilized 0.5 mol% of the optimal catalyst, [(R,R)-(iPrDuPhos)Co(η6-C6H6)][BArF4] in THF solution and produced sitagliptin in >99% yield with 97% ee. Cobalt catalysts were compatible with a range of solvents and maintained excellent activity and selectivity after standing in air in the solid state for two weeks. Deuterium labeling studies support an enamine-imine tautomerization process resulting in reduction of the metalated imine. Notably, state-of-the-art neutral bis(phosphine) cobalt precatalysts were ineffective, emphasizing the utility of a class of cationic cobalt precatalyst.  more » « less
Award ID(s):
1855719
PAR ID:
10320893
Author(s) / Creator(s):
; ; ; ;
Date Published:
Journal Name:
ACS Catalysis
Volume:
12
ISSN:
2155-5435
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; (, Dalton Transactions)
    Warren Piers (Ed.)
    Although cobalt( i ) bis-phosphine complexes have been implicated in many selective C–C bond-forming reactions, until recently relatively few of these compounds have been fully characterized or have been shown to be intermediates in catalytic reactions. In this paper we present a new practical method for the synthesis and isolation of several cobalt( i )-bis-phosphine complexes and their use in Co( i )-catalyzed reactions. We find that easily prepared ( in situ generated or isolated) bis-phosphine and (2,6- N -aryliminoethyl)pyridine (PDI) cobalt( ii ) halide complexes are readily reduced by 1,4-bis-trimethylsilyl-1,4-dihydropyrazine or commercially available lithium nitride (Li 3 N), leaving behind only innocuous volatile byproducts. Depending on the structures of the bis-phosphines, the cobalt( i ) complex crystallizes as a phosphine-bridged species [(P∼P)(X)Co I [μ-(P∼P)]Co I (X)(P∼P)] or a halide-bridged species [(P∼P)Co I [μ-(X)] 2 Co I (P∼P)]. Because the side-products are innocuous, these methods can be used for the in situ generation of catalytically competent Co( i ) complexes for a variety of low-valent cobalt-catalyzed reactions of even sensitive substrates. These complexes are also useful for the synthesis of rare cationic [(P∼P)Co I -η 4 -diene] + X − or [(P∼P)Co I -η 6 -arene] + X − complexes, which are shown to be excellent single-component catalysts for the following regioselective reactions of dienes: heterodimerizations with ethylene or methyl acrylate, hydroacylation and hydroboration. The reactivity of the single-component catalysts with the in situ generated species are also documented. 
    more » « less
  2. ; ; ; (, Book of Abstracts, 259th ACS National Meeting, Philadelphia, PA, March 22-26 2020.)
    Discovery of base metal-catalyzed methods for the preparation of chiral intermediates has garnered great attention. Recently, through a systematic study of activators and ligands, we have discovered Co(I)-catalyzed enantioselective heterodimerization of linear 1,3-dienes with ethylene and acrylates. In these studies, cationic cobalt(I) has been invoked as an active catalyst to carry out the transformation. However, the synthesis and isolation of such active Co(I)-complexes which could give insight into of reaction’s mechanism, remains challenging. Herein, we disclosed a reliable procedure for the synthesis and isolation of Co(I)-complexes and characterized them by UV-Vis spectroscopy and X-ray crystallography. The bis-phosphine ligated Co(I) complexes in presence of activators, performed the regio- and enantioselective hydroboration of 2- substituted 1,3-diene with pinacolborane (HBPin) to obtain homoallylic boronates (enantiomeric excess, ee >90%). In the absence of activators, these complexes do not catalyze the reaction suggesting the key role of cationic Co(I)-species in the catalytic cycle. Currently, these Co(I) complexes are being further utilized in the hydroacylation of 1,3-dienes with simple aliphatic aldehyde to produce enantiopure ketones. The comprehensive protocols for the synthesis of Co(I) complexes and its application in hydrovinylation, heterodimerization with acrylates, hydroboration, and hydroacylation of 1,3-dienes will be discussed. 
    more » « less
  3. ; ; (, Canadian Journal of Chemistry)
    null (Ed.)
    Diene self-exchange reactions of the 17-electron, formally cobalt(0) cyclooctadienyl precatalyst, (R,R)-(iPrDuPhos)Co(COD) (P2CoCOD, (R,R)-iPrDuPhos = 1,2-bis((2R,5R)-2,5-diisopropylphospholano)benzene, COD = 1,5-cyclooctadiene) were studied using natural abundance and deuterated 1,5-cyclooctadiene. Exchange of free and coordinated diene was observed at ambient temperature in benzene-d6 solution and kinetic studies support a dissociative process. Both neutral P2CoCOD and the 16-electron, cationic cobalt(I) complex, [(R,R)-(iPrDuPhos)Co(COD)][BArF4] (BArF4 = B[(3,5-(CF3)2)C6H3]4) underwent instantaneous displacement of the 1,5-cyclooctadiene ligand by carbon monoxide and generated the corresponding carbonyl derivatives. The solid-state parameters, DFT-computed Mulliken spin density and analysis of molecular orbitals suggest an alternative description of P2CoCOD as low-spin cobalt(II) with the 1,5-cyclooctadiene acting as a LX2-type ligand. This view of the electronic structure provides insight into the nature of the ligand substitution process and the remarkable stability of the neutral cobalt complexes toward protic solvents observed during catalytic alkene hydrogenation. 
    more » « less
  4. ; ; ; ; ; (, Journal of the American Chemical Society)
    ABSTRACT: Enantiopure homoallylic boronate esters are versatile intermediates because the C–B bond in these com-pounds can be stereospecifically transformed into C–C, C–O and C–N bonds. Regio- and enantioselective synthesis of these precursors from 1,3-dienes has few precedents in the literature. We have identified reaction conditions and ligands for the synthesis of nearly enantiopure (er >97:3 to >99:1) homoallylic boronate esters via a rarely seen cobalt-catalyzed [4,3]-hydroboration of 1,3-dienes. Monosubstituted or 2,4-disubstituted linear dienes undergo highly efficient, regio- and enanti-oselective hydroboration with HBPin catalyzed by [(L*)Co]+[BARF]–, where L* is typically a chiral bis-phosphine ligand with a narrow bite angle. Several such ligands (examples: i-PrDuPhos, QuinoxP*, Duanphos and, BenzP*) that give high enantioselectivities for the [4,3]-hydroboration product have been identified. In addition, the equally challenging problem of regioselectivity is uniquely solved with a dibenzooxaphosphole ligand, (R,R)-MeO-BIBOP. A cationic cobalt(I) complex of this ligand is a very efficient (TON >960) catalyst, while providing excellent regioselectivities (rr >98:2) and enantioselectiv-ities (er >98:2) for a broad range of substrates. A detailed computational investigation of the reactions using Co-complexes from two widely different ligands (BenzP* and MeO-BIBOP) employing B3LYP-D3 density functional theory provides key insights into the mechanism and the origins of selectivities. The computational results are in full agreement with the exper-iments. For the complexes we have examined thus far, the relative stabilities of the diastereomeric diene-bound complexes [(L*)Co(4-diene)]+ leads to the initial diastereofacial selectivity, which in turn is retained in the subsequent steps, providing exceptional enantioselectivity for the reactions. 
    more » « less
  5. ; ; ; ; ; ; ; (, Organometallics)
    Carbon dioxide hydrogenation with base to generate formate salts can provide a means of storing hydrogen in an energy dense solid. However, this application requires catalytic CO2 hydrogenation, which would ideally use an earth abundant metal catalyst. In this article, six new (CNC)CoIL2 pincer complexes were synthesized and fully characterized, including single crystal X-Ray diffraction analysis on four new complexes. These complexes contain an imidazole-based (1R) N-heterocyclic carbene (NHC) ring or a benzimidazole based NHC ring (2R) in the CNC pincer. The R group is para to N on the pyridine ring and been varied from electron withdrawing (CF3) to donating (Me, OMe) substituents. The L type ligands have included CO and phosphine ligands (in PPh32 and PMe32). Thus, two known Co complexes (1, 1OMe) and six new complexes (1Me, 1CF3, 2, 2OMe, PPh32, PMe32) were studied for the CO2 hydrogenation reaction. In general, the unsubstituted CNC pincer complexes bearing two carbonyl ligands led to the highest activity. The best catalyst, 2, remains active for over 16 h and produces a turnover number of 39,800 with 20 bars of 1:1 CO2 / H2 mixture at 60 °C. A computational study of the mechanism of CO2 hydrogenation is also reported. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email