Simple and highly diastereoselective access to 3,4-substituted tetrahydro-1,8-naphthyridines from Morita-Baylis-Hillman adducts

We disclose herein a facile and straightforward method to access 3,4-substituted tetrahydro-1,8-naphthyridines from Morita-Baylis-Hillman. The strategy is based on a tandem sequence involving a Michael addition reaction followed by an intramolecular S_NAr reaction on a silylated-Morita-Baylis-Hillman adduct. In a single step, a new cycle is formed and the relative stereochemistry of two new centers is controlled with good to excellent diastereoselectivity.     

Highly enantioselective and regioselective substitution of Morita-Baylis-Hillman carbonates with nitroalkanes

A highly enantioselective and regioselective substitution reaction of the Morita-Baylis-Hillman (MBH) carbonates with nitroalkanes catalyzed by a quinidine-derived tertiary amine-thiourea catalyst has been developed. The described method, which is different from most organocatalytic allylic substitutions of the MBH adducts to date, represents a novel approach to regioselectively functionalize the MBH adducts.     

Organocatalyzed regio- and enantioselective allylic trifluoromethylation of Morita-Baylis-Hillman adducts using Ruppert-Prakash reagent

The organocatalyzed regioselective allylic trifluoromethylation of Morita-Baylis-Hillman adducts using Ruppert-Prakash reagent was achieved in high to excellent yields via a successive S(N)2'/S(N)2' mode for the first time. The reaction was extended to the asymmetric allylic trifluoromethylation by the use of a bis-cinchona alkaloid catalyst with high enantioselectivities up to 94% ee.     

A highly efficient kinetic resolution of Morita-Baylis-Hillman adducts achieved by N-Ar axially chiral Pd-complexes catalyzed asymmetric allylation

Palladium complexes with an axially chiral N-Ar framework have been developed. These complexes showed high stereoselectivities in asymmetric allylic arylation to achieve the kinetic resolution of Morita-Baylis-Hillman adducts, affording up to 99% ee of (E)-allylation products and 92% ee of recovered Morita-Baylis-Hillman adducts.     

First chiral phosphoroamidite-phosphite ligands for highly enantioselective and versatile Pd-catalyzed asymmetric allylic substitution reactions

[reaction: see text] A series of phosphite-phosphoroamidite ligands, derived from readily available d-xylose, has been successfully applied for the first time in the Pd-catalyzed allylic substitution of several substrates with different steric and electronic properties, with high enantioselectivities (ee's up to 98) and activities in standard conditions.     

Bromoporphyrins as versatile synthons for modular construction of chiral porphyrins: cobalt-catalyzed highly enantioselective and diastereoselective cyclopropanation

5,10-Bis(2',6'-dibromophenyl)porphyrins bearing various substituents at the 10 and 20 positions were demonstrated to be versatile synthons for modular construction of chiral porphyrins via palladium-catalyzed amidation reactions with chiral amides. The quadruple carbon-nitrogen bond formation reactions were accomplished in high yields with different chiral amide building blocks under mild conditions, forming a family of D2-symmetric chiral porphyrins. Cobalt(II) complexes of these chiral porphyrins were prepared in high yields and shown to be active catalysts for highly enantioselective and diastereoselective cyclopropanation under a practical one-pot protocol (alkenes as limiting reagents and no slow addition of diazo reagents).     

Palladium-catalyzed regio- and enantioselective allylic alkylation of bis allylic carbonates derived from Morita-Baylis-Hillman adducts

Morita-Baylis-Hillman diene adducts are used as substrates in the palladium-catalyzed asymmetric allylic alkylation reaction with oxygen and carbon nucleophiles in good regio- and enantioselectivity.     

Chiral phosphine-catalyzed enantioselective construction of gamma-butenolides through substitution of Morita-Baylis-Hillman acetates with 2-trimethylsilyloxy furan

Chiral multifunctional phosphine (R)-N-(2'-diphenylphosphanyl-[1,1']binaphthalenyl-2-yl)methanesulfonamide L2 or (R)-N-(2'-diphenylphosphanyl-[1,1']binaphthalenyl-2-yl)acetamide L3 is an efficient catalyst in the allylic substitutions of MBH acetates 1 with 2-trimethylsilyloxy furan 2 to provide gamma-butenolides 3 in good to excellent yields and enantiomeric excesses in the presence of water.     

A facile and highly diastereoselective aziridination of chiral camphor n-enoylpyrazolidinones with n-aminophthalimide

Reaction of various chiral camphor N-enoylpyrazolidinones 2a-g with N-aminophthalimide in the presence of lead tetraacetate in CH(2)Cl(2) proceed smoothly afford the corresponding N-phthalimidoaziridines (3a-e, 4f-g) with excellent material yields (86-95%) at room temperature in 5 min. High levels of diastereoselectivities (up to >95:5 dr) were obtained. The solvent effect was investigated, and the auxiliary can be easily recovered in high yields under mild reaction conditions.     

A highly enantioselective and diastereoselective synthesis of cyclobutanes via boronic esters

[formula: see text] Deprotonation of enantiopure (R,R)-1,2-dicyclohexyl-1,2-ethanediol 1-chloro-4-cyanobutylboronates 5 with LDA followed by treatment with anhydrous magnesium bromide yields (R)-(trans-2-cyanocyclobutyl)boronic esters 7 in high diastereomeric and enantiomeric purity. No cyclobutane formation has been observed in the absence of at least a catalytic amount of magnesium halide.     

Gold-catalyzed highly enantioselective synthesis of axially chiral allenes

Axially chiral allenes are synthesized from chiral propargylamines catalyzed by KAuCl4 in high yields (up to 93% yield) and excellent enantioselectivities (up to 97% ee) in CH3CN at 40 degrees C. The reaction has been applied to the synthesis of novel allene-modified artemisinin derivatives with the delicate endoperoxide moieties remaining intact. A tentative mechanism regarding gold(I)-catalyzed intramolecular hydride transfer was proposed on the basis of deuterium-labeling experiments and ESI-MS analysis of the reaction mixture.     

Alkaloids-catalyzed regio- and enantioselective allylic nucleophilic substitution of tert-butyl carbonate of the Morita-Baylis-Hillman products

The alkaloids-catalyzed regio- and enantioselective allylic nucleophilic substitution reactions of tert-butyl carbonate of the Morita-Baylis-Hillman products with pronucleophiles are reported. A number of pronucleophiles, such as nitrogen, oxygen, and active carbon pronucleophiles have been used in this facile reaction. In general, the reaction proceeded efficiently to give the substitution product in good yields with high regioselectivity and medium enantioselectivity.     

Synthesis of planar chiral phosphapalladacycles by highly enantioselective transcyclopalladation

The first highly enantioselective synthesis of planar chiral ferrocene phosphapalladacycles was performed by high-yielding asymmetric transcyclopalladation with cobalt oxazoline palladacycles (COP). Use of di-mu-acetatobis[(eta5-(S)-(pR)-2-(2'-(4'-isopropyl)oxazolinyl)cyclopentadienyl-C1,N3')(eta4-tetraphenylcyclobutadiene)cobalt]dipalladium(II), followed by acetate/chloride ligand exchange, gave (pS)-di-mu-chloro[2-(2-dicyclohexylphosphino)phenylferroene-C1,P)dipalladium(II) (95% ee). Similarly, diastereomeric di-mu-acetatobis[(eta5-(S)-(pS)-2-(2'-(4'-tert-butyl)oxazolinyl)cyclopentadienyl-C1,N3')(eta4-tetraphenylcyclobutadiene)cobalt]dipalladium(II) led to the enantiomeric (pR)-phosphapalladacycle (95% ee), revealing the control of these reactions by the element of planar chirality in COP. The reactions were extended to the synthesis of (pS)- and (pR)-di-mu-chloro[2-(2-diphenylphosphino)phenylferroene-C1,P)dipalladium(II) (78 and 92% ee, respectively). In all cases, the palladium-free precursors to COP were recovered for recycling.     

Novel bifunctional chiral thiourea catalyzed highly enantioselective aza-Henry reaction

A novel bifunctional chiral thiourea organocatalyst bearing a glycosyl scaffold and a tertiary amino group was synthesized starting from readily available alpha-D-glucose. This thiourea was proven to be an effective organocatalyst for the asymmetric aza-Henry reaction between N-Boc imines and nitromethane. The corresponding adducts were obtained in good to excellent yields with excellent enantioselectivities (up to 99.8% ee). In addition, the reaction of nitroethane also proceeded smoothly with excellent enantioselectivity, albeit with low to good diastereoselectivities.     

Organocatalytic asymmetric transformations of modified Morita-Baylis-Hillman adducts

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 Br?nsted 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.     

The enantioselective Morita-Baylis-Hillman reaction and its aza counterpart

The development of asymmetric Morita-Baylis-Hillman (MBH) reactions has evolved dramatically over the past few years, parallel to the emerging concept of bifunctional organocatalysis. Whereas organocatalysis is starting to compete with metal-based catalysis in several important organic transformations, the MBH reaction belongs to a group of prototypical reactions in which organocatalysts already display superiority over their metal-based counterparts. This Minireview summarizes recent mechanistic insights and advances in the design and synthesis of small organic molecules for enantioselective MBH and aza-MBH reactions.     

Asymmetric substitutions of O-Boc-protected Morita-Baylis-Hillman adducts with pyrrole and indole derivatives

An efficient asymmetric substitution process of O-Boc-protected Morita-Baylis-Hillman adducts with various pyrrole and indole derivatives has been developed in the presence of (DHQD)(2)PYR in THF, affording the corresponding products in good to high yields (up to 99% yield) and moderate to high ee values (up to 92 and 96% ee) under mild conditions.     

Synthesis of protected chiral vicinal diaminoalcohols by diastereoselective intramolecular benzylic substitution from bistrichloroacetimidates

An efficient synthesis of chiral dihydrooxazines (2) from 1-aryl-2-amino-propane-1,3-diols (1) via the corresponding bistrichloroacetimidate intermediates has been developed. In this transformation, one trichloroacetimidate acts as a leaving group and the other acts as a nucleophile. The cyclization proceeds through an SN1 mechanism to provide trans-dihydrooxazines with complete diastereoselectivity irrespective of the absolute configuration of the benzylic alcohol. The transformation of 2 into other selectively protected aminodiols is also documented. [reaction: see text].     

A diastereoselective and concise synthesis of functionalised vinyl epoxides with a Morita-Baylis-Hillman backbone

A highly diastereoselective organocatalytic synthesis of unique functionalised vinyl epoxides, displaying a Morita-Baylis-Hillman backbone, has been developed by means of an user friendly sulfonium ylide epoxidation of aldehydes from a readily available alpha-(bromomethyl)acrylamide derivative. The first result in the asymmetric version is discussed.