Enantioselective, Organocatalytic Morita-Baylis-Hillman and Aza-Morita-Baylis-Hillman Reactions: Stereochemical Issues

Abstract

Conscious of the importance that stereochemical issues may have on the design of efficient organocatalyts for both Morita-Baylis-Hillman and aza-Morita-Baylis-Hillman reaction we have analyzed them in this minireview. The so-called standard reactions involve “naked” enolates which therefore should lead to the syn adducts as the major products, irrespective of the E, Z stereochemistry of the enolate. Accordingly, provided the second step is rate determining step, the design of successful bifunctional or polyfunctional catalysts has to consider the geometrical requirements imposed by the transition structures of the second step of these reactions. On the other hand, MBH and aza-MBH reactions co-catalyzed by (S)-proline and a secondary or tertiary amine (co-catalyst) involve the aldol-type condensation of either a 3-amino-substituted enamine, dienamine, or both, depending on the cases. A Zimmerman-Traxler mechanism defines the stereochemical issues regarding these co-catalyzed condensations which parallel those of the well established (S)-proline catalyzed aldol-like reactions.

Mechanochemistry assisted asymmetric organocatalysis: A sustainable approach

“…The Morita–Baylis–Hillman (MBH) reaction provides a very useful and interesting method for the synthesis of β-hydroxycarbonyl compounds with an α-alkylidene group [49–53]. Mechanochemical methods of neat grinding and liquid-assisted grinding (LAG) have been applied to the synthesis of mono- and bis(thiourea)s in quantitative yield by using the click coupling of aromatic or aliphatic diamines with aromatic isothiocyanates (Scheme 9) [54].…”

Development of Tartaric Acid Derived Hydrogen-Bond Donors

“…13b,14 The condensation of 8 with diketone 20 furnished the pyrrole derivative 21 in excellent yield (Scheme 5). As C 2 -symmetric bis-thiourea derivatives 15 have been successfully utilized as organocatalysts in the asymmetric Morita-Baylis-Hillman 16 (MBH) reaction we synthesized the corresponding tartaric acid derived bis-thiourea 22. The diamine 10 was reacted with two equivalents of 4 furnishing the bis-thiourea 22 in excellent yield (95%, Scheme 6).…”

Constructing Quaternary Centers of Chirality: The Lanthanide Way to Trifluoromethyl-Substituted Tertiary Alcohols

“…We have discussed aldol and nitroaldol additions, Friedel-Crafts and ene reactions, and the addition of alkyl, vinyl, allyl, alkynyl, or aryl organometallics. Even though these achievements clearly show that it is possible to discriminate between the prochiral faces of these compounds by an appropriate choice of the reagent/catalyst pair, it is worth noting that there is a lack of protocols for cyanation or for the addition of functionalized carbon nucleophiles, such as thioacetal anions, the zwitterionic enolates characteristic of the Morita-Baylis-Hillman reaction, 103 or other compounds capable of providing access to a variety of highly valuable bifunctional products. Moreover, in many cases no detailed mechanistic information is currently available, so that future improvements and further developments will have to follow a trial-anderror approach.…”