Organocatalytic asymmetric transformations of modified Morita–Baylis–Hillman adducts

Abstract

Chiral Lewis basic tertiary amines or phosphines can enable properly modified Morita-Baylis-Hillman (MBH) adducts to undergo asymmetric allylic substitutions with a wide range of nucleophiles. In addition, assisted by a Brønsted base, chiral Lewis bases can also catalytically convert modified MBH adducts into allylic ylides, which can be engaged in a variety of asymmetric annulation reactions. This tutorial review will focus on such chiral Lewis base-catalysed asymmetric transformations of MBH adducts, especially those developed over the past five years, allowing for the rapid construction of densely functionalised chiral molecules with high levels of regio- and stereoselectivities.

One-Pot Two-Step Organocatalytic Asymmetric Synthesis of Spirocyclic Piperidones via Wolff Rearrangement–Amidation–Michael–Hemiaminalization Sequence

“…Halogen substitutions such as -F, -Cl, and -Br at the meta or para positions of aryl groups in enal 3 (entries 2-5) gave better yields and stereoselectivities than such substitutions at the ortho position (entries 6 and 7). Strong electron-withdrawing aryl groups on enal 3 (entries 8 and 9) gave slightly higher yields and stereoselectivities than electron-donating aryl groups (entries [10][11][12]. The heteroaromatic group furan led to the desired product 5m with high ee and good dr value (entry 13).…”

“…Over the past decade, asymmetric organic catalysis [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17], quite powerful for synthesizing various heterocyclic molecules, has formed the basis of several elegant approaches to construct chiral single-heterocycle piperidine skeletons with high efficiency and low toxicity under environmentally friendly conditions . In contrast, relatively few organocatalytic methods have been described to stereo-selectively form spirocyclic piperidine derivatives [30][31][32][33][34][35][36], particularly ones with a quaternary stereocenter [37][38][39].…”

“…Strong electron-withdrawing aryl groups on enal 3 (entries 8-9) gave slightly higher 91 yields and stereoselectivities than electron-donating aryl groups (entries [10][11][12] Using these optimized conditions (Table 1, entry 12), we explored the scope and limitations of this method using α,β-unsaturated aldehyde 3, cyclic 2-diazo-1,3-diketone 1 and primary amine 2 (Table 2). Generally, the reaction was flexible in affording the desired spirocyclic piperidones.…”

P-C bond formation in reactions of Morita-Baylis-Hillman adducts with phosphorus nucleophiles

“…Actually, those transformations that produce only intermediate allylphosphonium cations (and further ylides) from phosphines have been studied mostly. 30 In these cases, the C-P is formed temporarily, typically in situ, and then released upon the final transformation step, e.g., in the Wittig reaction. This chemistry is beyond the scope of this review, as we are merely focused on targeting the final organophosphorus materials containing a permanent C-P bond.…”

Intramolecular Baylis-Hillman reaction: synthesis of heterocyclic molecules

“…(5) It produces molecules containing a minimum of three proximal functional groups which are of tremendous potential in synthetic and mechanistic organic chemistry. In fact the wide popularity and applicability of this reaction can be easily understood by publications of a number of major [14][15][16][17][18][19][20][21][22] and mini reviews [23][24][25][26][27][28][29][30] and more than 3200 research articles during the past three decades.…”