Substrate-Controlled Michael Additions of Chiral Ketones to Enones

Abstract

Substrate-controlled Michael additions of the titanium(IV) enolate of lactate-derived ketone 1 to acyclic α,β-unsaturated ketones in the presence of a Lewis acid (TiCl4 or SnCl4) provide the corresponding 2,4-anti-4,5-anti dicarbonyl compounds in good yields and excellent diastereomeric ratios. Likely, the nucleophilic species involved in such additions are bimetallic enolates that may add to enones through cyclic transition states. Finally, further studies indicate that a structurally related β-benzyloxy chiral ketone can also participate in such stereocontrolled conjugate additions.

Substrate‐Controlled Michael Additions of Titanium Enolates from Chiral α‐Benzyloxy Ketones to Conjugated Nitroalkenes

“…By taking advantage of our experience with substrate‐controlled Michael additions to enones, we initially assessed the Lewis acid mediated reaction of lactate‐derived ketone 1 to β‐nitrostyrene ( a ). Surprisingly, and in spite of the strong character of β‐nitrostyrene ( a ) as a Michael acceptor, the simple reaction with titanium(IV) enolate from 1 did not produce any Michael adduct, and the starting materials were recovered unchanged (Table , Entry 1).…”

“…Therefore, by considering that titanium(IV) enolates from chiral α‐benzyloxy ketones take part in highly stereocontrolled aldol reactions, we envisaged that they might also participate in diastereoselective Michael reactions. We were pleased to discover that enones are excellent acceptors and afforded the corresponding 1,5‐dicarbonyl compounds in high yields and diastereomeric ratios [Scheme , Equation (1)] . Then, because α,β‐unsaturated nitro derivatives are more active Michael acceptors than enones, and also that there are various transformations available for the nitro group, we hypothesized that substrate‐controlled Michael additions of the aforementioned chiral ketones to conjugated nitroalkenes might afford the corresponding adducts, which could in turn be easily converted into a range of enantiomerically pure intermediates.…”

Titanium Enolate Chemistry at the Beginning of the 21st Century

“…The described procedure led to new δ‐oxo‐α‐seleno esters 66 in good yields (Scheme ) 101a. More recently, application of protected α‐hydroxy ketones led to the 2,4‐ anti ‐4,5‐ anti dicarbonyl adducts in good yields and with excellent diastereomeric ratios 101b…”

PdCl2/CuCl2/Bi(OTf)3‐promoted Construction of Sulfonyl Dibenzooxabicyclo[3.3.1]nonanes and Arylnaphthalenes via Intramolecular Annulation of Sulfonyl o‐Allylarylchromanones

“…Among these diverse kinds of reaction routes, a number of synthetic efforts have attempted to control one factor or variant to generate different products with approximate or distinct skeletons in recent reports. These adjusting factors included temperature, [1][2][3][4][5][6][7][8][9][10][11][12][13][14] catalyst, [15][16][17][18][19][20][21] additive (e. g. ligand, [22][23][24][25] base [26][27] and reagent [28][29][30][31] ) and solvent. [32][33][34][35] On the basis of the abovementioned investigations, we found that controlling the temperature change is a simple, economical and direct protocol for affecting the formation of different products in comparison with other variables.…”