Combination of Enantioselective Metal Catalysis and Organocatalysis: Enantioselective Sequential Hydroformylation/ Aldol Reactions

Abstract

This work reports the possibility of controlling the sense of enantio-and diastereoinductions in the sequential hydroformylation and aldol reactions via the judicious combination of a chiral metal catalyst with a chiral organocatalyst. The diastereoselectivity of the reaction between styrene, syngas and acetone can be increased by using a matched pair of catalysts, [rhodium/A C H T U N G T R E N N U N G (2S,4S)-Chiraphite]/(S)-organocatalyst and decreased, but not inverted, by using a mismatched pair of catalysts,Keywords: aldol reaction; asymmetric catalysis; hydroformylation; organocatalysis; tandem reactions In order to achieve the highest possible efficiency in enantioselective chemical transformations, the number of steps must be kept to a minimum and the yield, regio-, enantio-and diastereoselectivities of each step should approach 100%. To meet this enormous challenge, several reactions can be combined in tandem reaction sequences.[1] Moreover, multiple chiral catalysts operating simultaneously could circumvent the time and yield losses associated with the isolation and purification of stereoisomers in multistep sequences.In contrast to the major progress made in asymmetric multicatalysis using multimetallic, [2] multiorganocatalytic [3] or metal-enzyme systems, [4] very few reports exist on the combination of metal with organocatalysts to accomplish an asymmetric reaction.[5] Recently, achiral metal catalyst/chiral organocatalyst [6] and chiral metal catalyst/achiral organocatalyst catalytic systems have been reported. [7] However, a methodology where the absolute configuration of one stereogenic center in the product is controlled by a chiral metal-ligand complex and the configuration of another stereogenic center is controlled by a chiral organocatalyst has not been very successful so far.[6g] Considering the multitude of enantioselective reactions catalyzed by either metal catalysts (reductions, oxidations, s-bond insertions, p-bond activation, Lewis acid reactions) [8] or organocatalysts (enamine, iminium, hydrogen-bonding, SOMO, counter ion catalysis) [9] we envision a tremendous potential for the creation of unique multicatalytic systems to influence chirality in reaction products.In this report we present the combination of a chiral rhodium catalyst with a chiral organocatalyst in an enantioselective sequential hydroformylation followed by an aldol reaction (Scheme 1).The sequential conversion of styrene with syngas and acetone to aldol product 3 was chosen as a model reaction. We presumed that exposure of styrene to a chiral Rh catalyst under hydroformylation conditions would generate an enantioenriched aldehyde 2, which can be intercepted in the second catalytic cycle by the chiral enamine derived from acetone and (S)-proline. We envisioned that control of the sense of enantioand diastereoinductions (e.g., S vs. R, anti vs. syn) could be achieved via judicious selection of the chiral catalysts involved in each catalytic cycle. The synthetic plan relied on finding optimal conditions for ...

Tandem Hydroformylation/Acyloin Reaction – The Synergy of Metal Catalysis and Organocatalysis Yielding Acyloins Directly from Olefins

“…Therefore, the combination of transition metal‐catalysed hydroformylation with further reactions is still a field of high interest in chemistry as seen in reports that have been recently published 3. The specific combination of hydroformylation with organocatalytic reactions is displayed only in few examples4 with a main focus on tandem hydroformylation/aldol reaction4a–d.…”

Organocatalyzed Aldol Reactions

“…The versatility of this catalyst was shown by its application in the reaction of trifluoromethyl ethyl hemiacetal (262) and aromatic methyl ketones (263) to achieve the corresponding aldol product with good results (Scheme 3.62) [315]. Also, a tandem process consisting of an hydroformylation catalyzed by a rhodium catalyst a d an aldol reaction has been carried out using catalyst 261, with up to 99% ee of the aldol products being achieved [316]. Compound 265 (20 mol%; Figure 3.12) was evaluated in the aldol reaction between acetone (52a, 27 equiv) and aromatic aldehydes in DMSO at 25 • C, with low yields being achieved (11-72%, 70-91% ee), because of the formation of dehydratation products [317].…”

An Unprecedented 5‐Connected Self‐penetrated Cadmium(II) Coordination Polymer: Synthesis, Crystal Structure, and Luminescent Property

“…Therefore, the combination of transition metal‐catalysed hydroformylation with further reactions is still a field of high interest in chemistry as seen in reports that have been recently published 3. The specific combination of hydroformylation with organocatalytic reactions is displayed only in few examples4 with a main focus on tandem hydroformylation/aldol reaction4a–d.…”