Premium
Enzymatic Cross‐Benzoin‐Type Condensation of Aliphatic Aldehydes: Enantioselective Synthesis of 1‐Alkyl‐1‐hydroxypropan‐2‐ones and 1‐Alkyl‐1‐hydroxybutan‐2‐ones
Author(s) -
Di Carmine Graziano,
Bortolini Olga,
Massi Alessandro,
Müller Michael,
Bernacchia Giovanni,
Fantin Giancarlo,
Ragno Daniele,
Giovannini Pier Paolo
Publication year - 2018
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201800357
Subject(s) - chemistry , propionaldehyde , aldehyde , enantioselective synthesis , benzoin , acetaldehyde , catalysis , organic chemistry , stereoselectivity , alkyl , medicinal chemistry , ethanol
Benzoin‐type reactions have been intensively exploited as a synthetic strategy for the preparation of α ‐hydroxy ketones. Thiamine diphosphate (ThDP) dependent enzymes are excellent catalysts for asymmetric versions of such reaction types. In particular, in cross‐benzoin condensations of aromatic reactants and mixed aromatic/aliphatic reactions, use of these enzymes has resulted in high levels of chemo‐, regio‐ and stereoselectivity. The present work, which confirms this trend for aliphatic reactants, outlines results obtained in the formal cross‐benzoin‐type condensation of the ‘umpoled’ acetaldehyde and propionaldehyde with various aliphatic aldehydes catalyzed by the ThDP‐dependent enzyme acetoin:dichlorophenolindophenol oxidoreductase (Ao:DCPIP OR). In these reactions, 3‐hydroxy‐3‐methylbutan‐2‐one (methylacetoin) was used as the activated acetaldehyde donor, while 4‐hydroxy‐4‐methylhexan‐3‐one was employed for the first time as the precursor of activated propionaldehyde. With the exception of 3‐hydroxypentan‐2‐one and 3‐hydroxyhexan‐2‐one, which were obtained in almost racemic form by the condensation of methylacetoin with propanal and butanal, respectively, all other products achieved from reactions performed using the same donor with more hindered aldehyde acceptors were obtained with high conversions (89–99%) and in good to high enantiomeric excess (72–99% ee ). In a similar way, high conversions (75–99%) and good ee (76–99%) were observed in reactions performed with the same set of aldehyde acceptors, but using 4‐hydroxy‐4‐methylhexan‐3‐one as propionyl anion donor. This is the first time that most of the products described herein have been prepared via benzoin‐type condensation.