Palladium-catalyzed regio-, diastereo-, and enantioselective allylic alkylation of acylsilanes with monosubstituted allyl substrates

Acylsilanes as a new type of "hard" carbon prenucleophile reacted with monosubstituted allyl reagents under Pd-catalyzed asymmetric allylic alkylation reaction conditions to provide products with high regio-, diastereo-, and enantioselectivities. The usefulness of the protocol has been demonstrated by the ready conversion of the allylated products into the corresponding alcohols, esters, and ketones with retention of stereochemistry as well as by the enantioselective synthesis of cis-3-ethyl-4-phenylpiperidine and cinnamomumolide.     

Ir-catalyzed regio- and enantioselective Friedel-Crafts-type allylic alkylation of indoles

Highly regio- and enantioselective Ir-catalyzed Friedel-Crafts type allylic alkylation of indoles have been realized using [Ir(COD)Cl]2/phosphoramidite ligand 1a, affording the branched products with up to >97/3 branched-linear ratio and 92% ee.     

Chemo-, regio-, and enantioselective Pd-catalyzed allylic alkylation of indolocarbazole pro-aglycons

[reaction: see text] Monosubstituted isomerically pure indolopyrrolocarbazole precursors have been prepared via palladium-catalyzed asymmetric allylic alkylation methodology, employing both achiral cyclopentenyl electrophiles and chiral glycal derivatives. Chemoselective allylation of (bis)indole lactam pro-aglycon 3 allows access to N-distally substituted indolopyrrolocarbazole derivatives; glyoxamide precursor 14 provides entry into N-proximally substituted derivatives.     

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.     

Ir-catalyzed regio- and enantioselective decarboxylative allylic alkylations

[Ir(COD)Cl]2/phosphoramidite ligand 1a was found to be an efficient catalytic system for the highly regio- and enantioselective decarboxylative alkylation of gamma-substituted allyl beta-ketocarboxylates, affording the branched products with up to >99/1 branched-linear ratio and 96% ee.     

Highly regio- and enantioselective palladium-catalyzed allylic alkylation and amination of dienyl esters with 1,1'-P,N-ferrocene ligands

[reaction, structure: see text] Pd-catalyzed asymmetric allylic alkylation of dienyl acetates 1 and amination of allyl acetates 2 provides the corresponding chiral products in high regio- and enantioselectivities using 1,1'-P,N-ferrocenes L1a and L2d as ligands, respectively.     

Ligand controlled highly regio- and enantioselective synthesis of alpha-acyloxyketones by palladium-catalyzed allylic alkylation of 1,2-enediol carbonates

The palladium catalyzed decarboxylative asymmetric allylic alkylation of allyl 1,2-enediol carbonates 1 can decompose to either alpha-hydroxyketones 3 or alpha-hydroxyaldehydes 4. The product distribution is largely controlled by the ligand. Using Lnaph in DME we exclusively obtained the ketone product in good to excellent yields and high enantiomeric excesses. The reaction proceeds under extremely mild conditions, so we can have a broad range of choices of OR. Besides the commonly used protection groups such as OAc and OPiv, a more functionalized group such as methyl but-2-enoyl group can also be used, downstream process of which can afford other synthetically interesting structures.     

Highly diastereo- and enantioselective construction of phthalide-oxindole hybrids bearing vicinal quaternary chiral centers via an organocatalytic allylic alkylation

A diastereo- and enantioselective synthesis of phthalide-oxindole hybrids including congested adjacent quaternary chiral centers was demonstrated through a Lewis base catalyzed asymmetric allylic alkylation reaction of Morita–Baylis–Hillman carbonates of isatins and 3-cyanophthalides. The various hybrid molecules with two valuable pharmacophores-combined frameworks can be obtained in good to high diastereo- and enantioselectivities.     

Palladium-catalyzed regio- and enantioselective fluorination of acyclic allylic halides

This report describes the Pd(0)-catalyzed fluorination of linear allylic chlorides and bromides, yielding branched allylic fluorides in high selectivity. Many of the significant synthetic limitations previously associated with the preparation of these products are overcome by this catalytic method. We also demonstrate that a chiral bisphosphine-ligated palladium catalyst enables highly enantioselective access to a class of branched allylic fluorides that can be readily diversified to valuable fluorinated products.     

Iridium(I)-catalyzed regio- and enantioselective allylic amidation

Ir(I)-catalyzed intermolecular allylic amidation of ethyl allyl carbonates with soft nitrogen nucleophiles under completely ‘salt-free’ conditions is described. A combination of [Ir(COD)Cl]₂, a chiral phosphoramidite ligand L^∗, and DBU as a base in THF effects the reaction. The reaction appears to be quite general, accommodating a wide variety of R-groups and soft nitrogen nucleophiles, and proceeds with excellent regio- and enantioselectivities to afford the branched N-protected allylic amines. The developed reaction was conveniently utilized in the asymmetric synthesis of N-Boc protected α- and β-amino acids as well as (−)-cytoxazone.     

Highly enantioselective organocatalytic sulfenylation of 3-aryloxindoles

An organocatalytic asymmetric sulfenylation of 3-aryloxindoles with N-(sulfanyl)succinimides has been developed by using commercially available (DHQD)(2)PHAL as catalyst. Various chiral 3-benzylthio-, alkylthio-, and arylthio-substituted oxindoles, containing 3,3-disubstituted quarternary carbon stereocenters, could be obtained in high enantioselectivities (85-97% ee). Furthermore, the opposite enantiomers of the sulfenylated products were readily accessible with equal excellent enantioselectivities (86-95% ee) by replacing the catalyst with (DHQ)(2)PHAL.     

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.     

Highly enantioselective Pd-catalyzed allylic alkylation of indoles using Sulfur-MOP ligand

The preparation of various (R)-Sulfur-MOP ligands with aryl and alkyl substituents on sulfur, and the application of these ligands to Pd-catalyzed asymmetric allylic alkylation of indoles is reported. The sulfur substituent served as an effective stereocontrol element, and in the case of the 2-i-PrPh substituent on sulfur, the allylation products from an array of simple and substituted indoles were obtained with high enantioselectivity (up to 95% ee).     

Organocatalyzed direct aldol condensation using l-proline and BINAM-prolinamides: regio-, diastereo-, and enantioselective controlled synthesis of 1,2-diols

Recoverable BINAM-prolinamide derivatives, as well as l-proline, give results complementary to antibodies when used as organocatalysts for aldol reactions between aldehydes and α-alkoxyacetones driving regioselectively to anti/syn-1,2-diols. The formation of the iso-regioisomer is suppressed using α-hydroxyacetone in DMSO at rt, achieving the corresponding anti-1,2-diol with ee’s up to 85%. For α-alkoxyacetones (methoxy, benzyloxy, and tert-butyldimethylsilyloxy), the highest regio- and diastereoselectivity is achieved using α-methoxyacetone in DMF at 0 °C; the enantiomeric excess for the anti-1,2-isomer being up to 98%.     

Synthesis of (-)-Delta9-trans-tetrahydrocannabinol: stereocontrol via Mo-catalyzed asymmetric allylic alkylation reaction

[reaction: see text] Delta9-THC is synthesized in enantiomericaly pure form, where all of the stereochemistry is derived from the molybdenum-catalyzed asymmetric alkylation reaction of the extremely sterically congested bis-ortho-substituted cinnamyl carbonate in high regio- and enantioselectivity.     

A case for enantioselective allylic alkylation catalyzed by palladium nanoparticles

Palladium nanoparticles (4 nm, fcc) were prepared through decomposition of [Pd2(dba)3] by H2 in the presence of a chiral xylofuranoside diphosphite. These particles catalyze the allylic alkylation of rac-3-acetoxy-1,3-diphenyl-1-propene with dimethyl malonate leading to an almost total conversion of the (R) enantiomer and almost no reaction with the (S). This gives rise to 97% ee for the alkylation product and a kinetic resolution of the substrate recovered with ca. 90% ee. This behavior was compared to that of a molecular catalyst at various dilutions, and the differences between the two systems are discussed. This is the first colloidal system shown to display such a high enantioselectivity besides the well-known Pt/cinchonidine system.