Chong-Dao Lu

Three-component reactions of sulfonylimidates, silyl glyoxylates and N-tert-butanesulfinyl aldimines: an efficient, diastereoselective, and enantioselective synthesis of Cyclic N-sulfonylamidines.

Three-component coupling reactions of sulfonylimidates, silyl glyoxylates and N-tert-butanesulfinyl aldimines efficiently provide cyclic N-sulfonylamidines containing free endocyclic N-H. The formation of two C-C bonds (contiguous stereogenic carbons), one O-Si bond, and one C-N bond, together with the cleavage of the chiral auxiliary (tert-butanesulfinyl group), occurs with excellent chemoselectivity, diastereoselectivity, and enantioselectivity in this one-pot cascade transformation.

Efficient Synthesis of α-Tertiary α-Silylamines from Aryl Sulfonylimidates via One-Pot, Sequential C–Si/C–C Bond Formations

An efficient and flexible route for the synthesis of α-tertiary (α,α-dibranched) α-silylamines via sequential reactions of sulfonylimidates using readily available phenyldimethylsilyllithium and Grignard reagents is described. The procedure allows successive formation of C-Si/C-C bonds in a single flask.

Efficient Synthesis of α-Quaternary α-Hydroxy-β-amino Esters via Silyl Glyoxylate-Mediated Three-Component Reactions

An efficient method has been developed for the enantioselective synthesis of fully protected α-quaternary α-hydroxy-β-amino esters via the coupling of three components: aryl Grignard reagents (or methyllithium), silyl glyoxylate, and N-tert-butanesulfinyl imines. This protocol enables successive formation of two C-C bonds and two adjacent chiral carbons with high stereocontrol in a one-pot operation.

Asymmetric Synthesis of cis-2-Aminocyclopropanols by Intramolecular Mannich Addition of Silyloxy Benzyl Carbanions

An efficient, highly diastereoselective method for the preparation of protected cis-2-aminocyclopropanols from N-tert-butanesulfinyl ketimines and various aryl acylsilanes is described. A tandem process for carbon-carbon bond formation via nucleophilic addition to acylsilanes, Brook rearrangement, and intramolecular Mannich reaction has been developed.

Diethyl Phosphite Initiated Coupling of α-Ketoesters with Imines for Synthesis of α-Phosphonyloxy-β-amino Acid Derivatives and Aziridine-2-carboxylates.

Coupling of α-ketoesters with imines initiated by diethyl phosphite in the presence of alkaline metal hexamethyldisilazides is reported. Base-promoted addition of diethyl phosphite to α-ketoesters, followed by [1,2]-phosphonate/phosphate rearrangement, generates α-phosphonyloxy enolates that are subsequently intercepted by imines. The use of suitable azomethine coupling partners allows selective construction of syn-α-hydroxy-β-amino acid derivatives or trans-aziridine-2-carboxylates in high yields with excellent diastereoselectivities.

P(NMe2)3-Mediated Aziridination of Imines with α-Ketoesters for Synthesis of Aziridine-2-carboxylates

Aziridination of N-sulfonyl imines with α-ketoesters in the presence of P(NMe2)3 is reported. Adducts derived from trivalent phosphorus reagents and α-ketoesters are effectively intercepted by imines, affording a range of aziridine-2-carboxylates. The diastereoselectivity of the reaction depends on steric hindrance from substituents on the substrates.

Diastereoselective synthesis of 2-methoxyimidoyloxiranes via dimethyl phosphite-mediated coupling of α-keto N-sulfinyl imidates with aldehydes

Dimethyl phosphite-initiated coupling of α-keto N-tert-butylsulfinyl imidates with aldehydes is reported. The epoxide formation involves a cascade transformation initiated by base-promoted addition of phosphite to α-ketoimidates, followed by [1,2]-phospha-Brook rearrangement. This generates α-phosphonyloxy enolates that are subsequently intercepted by aldehydes, leading to [1,4] O→O dialkoxyphosphinyl migration and finally to intramolecular ring closure. This protocol was used to synthesize a range of enantioenriched trans-α,β-epoxy imidates in moderate to high yields with excellent diastereoselectivities.

Stereoselective Synthesis of Enantioenriched 2-Chloro-2-aroylaziridines by Cascade Reaction between Aryl Nitriles, Silyldichloromethanes, and tert-Butanesulfinylimines

The cascade coupling of aryl nitriles, silyldichloromethanes, and tert-butanesulfinylimines is described, in which silyldichloromethyllithiums, generated from silyldichloromethanes in the presence of lithium diisopropylamide, undergo nucleophilic addition with aryl nitriles and subsequent [1,3]-aza-Brook rearrangement to give dichlorocarbanions bearing α-N-silyl imine (or their 1-azaenolate equivalents), which are then trapped by tert-butanesulfinylimines via an aza-Darzens-type transformation, affording enantioenriched 2-chloro-2-aroylaziridines after acidic hydrolysis of the N-silyl imine group. The stereochemistry of this cascade reaction can be tuned by selecting appropriate silyl groups on the silyldichloromethanes and altering the order of addition of the imines and the hexamethylphosphoramide additive.

Silyllithium-Initiated Coupling of α-Ketoamides with tert-Butanesulfinylimines for Stereoselective Synthesis of Enantioenriched α-(Silyloxy)-β-amino Amides

A silyllithium-initiated coupling of α-ketoamides with tert-butanesulfinylimines was developed for the efficient, stereoselective synthesis of enantioenriched α-(silyloxy)-β-amino amides. Nucleophilic addition of silyllithium to α-ketoamides, followed by 1,2-Brook rearrangement, generates nucleophilic enolates, which are then intercepted by chiral imines to provide three-component coupling products. Use of α-ketoamides is critical for achieving high yields and diastereoselectivities in the resulting α-hydroxy-β-amino acid derivatives.

Dialkyl Phosphite-Initiated Cyclopropanation of α,β-Unsaturated Ketones Using α-Ketoesters or Isatin Derivatives

Efficient cyclopropanation of α,β-unsaturated ketones using α-ketoesters or isatin derivatives is reported. The cyclopropanation reaction occurs via a cascade transformation that starts with addition of deprotonated dialkyl phosphite to the keto groups of α-ketoesters or isatin derivatives, followed by [1,2]-phosphonate/phosphate rearrangement to generate α-phosphonyloxyenolate intermediates, which are trapped by α,β-unsaturated ketones via Michael addition/ring closure. This protocol was used to synthesize tetra-substituted cyclopropanes with a 1,2-cis-1,3-trans configuration in high yield with excellent diastereoselectivity.