Dual Palladium(II)/Tertiary Amine Catalysis for Asymmetric Regioselective Rearrangements of Allylic Carbamates

The streamlined catalytic access to enantiopure allylic amines as valuable precursors towards chiral β‐ and γ‐aminoalcohols as well as α‐ and β‐aminoacids is desirable for industrial purposes. In this article an enantioselective method is described that transforms achiral allylic alcohols and N‐tosylisocyanate in a single step into highly enantioenriched N‐tosyl protected allylic amines via an allylic carbamate intermediate. The latter is likely to undergo a cyclisation‐induced [3,3]‐rearrangement catalysed by a planar chiral pentaphenylferrocene palladacycle in cooperation with a tertiary amine base. The otherwise often indispensable activation of palladacycle catalysts by a silver salt is not required in the present case and there is also no need for an inert gas atmosphere. To further improve the synthetic value, the rearrangement was used to form dimethylaminosulfonyl‐protected allylic amines, which can be deprotected under non‐reductive conditions.     

Anti-Markovnikov Hydroamination of Racemic Allylic Alcohols to Access Chiral γ-Amino Alcohols

A ruthenium-catalyzed formal anti-Markovnikov hydroamination of allylic alcohols for the synthesis of chiral γ-amino alcohols is presented. Proceeding via an asymmetric hydrogen-borrowing process, the catalysis allows racemic secondary allylic alcohols to react with various amines, affording enantiomerically enriched chiral γ-amino alcohols with broad substrate scope and excellent enantioselectivities (68 examples, up to >99 % ee).     

Allylic Imidate Rearrangements Catalyzed by Planar Chiral Palladacycles

The discovery that palladacycles are efficient catalysts for the allylic imidate rearrangement has resulted in the successful application of several such complexes to this reaction based on planar chiral iron and cobalt containing metallocenes. These palladacycles enable the efficient and highly enantioselective synthesis of a wide variety of protected allylic amines, which are valuable building blocks for use in asymmetric synthesis.     

Asymmetric Allylic Alkylation of β‐Ketoesters with Allylic Alcohols by a Nickel/Diphosphine Catalyst

Asymmetric allylic alkylation of β‐ketoesters with allylic alcohols catalyzed by [Ni(cod)₂]/(S)‐H₈‐BINAP was found to be a superior synthetic protocol for constructing quaternary chiral centers at the α‐position of β‐ketoesters. The reaction proceeded in high yield and with high enantioselectivity using various β‐ketoesters and allylic alcohols, without any additional activators. The versatility of this methodology for accessing useful and enantioenriched products was demonstrated.     

Ir-catalyzed asymmetric allylic amination using chiral diaminophosphine oxides

An Ir-catalyzed asymmetric allylic amination using chiral diaminophosphine oxide is described. Asymmetric allylic amination of terminal allylic carbonates proceeded in the presence of 2 mol % of Ir catalyst, 2 mol % of chiral diaminophosphine oxide, 5 mol % of NaPF₆, and BSA, affording the chiral branched allylic amines in up to 95% ee.     

Enantioselective Allylic Amination of Morita‐Baylis‐Hillman Acetates Catalyzed by Chiral Thiourea‐Phosphine

The enantioselective allylic amination of Morita‐Baylis‐Hillman acetates catalyzed by chiral cyclohexane‐based thiourea‐phosphine catalysts was investigated. In the presence of 20 mol% rosin‐derived thiourea‐phosphine 3j , the chiral amines were obtained in up to 88% yield and up to 85% ee.     

Catalytic asymmetric rearrangement of allylic N-aryl trifluoroacetimidates. A useful method for transforming prochiral allylic alcohols to chiral allylic amines

[reaction: see text] A useful method for the conversion of prochiral allylic alcohols to chiral allylic amines of high enantiopurity is reported. N-(4-Methoxyphenyl)trifluoroacetimidates are excellent substrates for the palladium(II)-catalyzed allylic imidate rearrangement as the allylic trifluoroacetamide products can be deprotected in two steps to provide chiral nonracemic allylic amines. Di-mu-chlorobis[(eta(5)-(S)-(pR)-2-(2'-(4'-isopropyl))oxazolinylcyclopentadienyl,1-C,3'-N))(eta(4)-tetraphenylcyclobutadiene)cobalt]dipalladium (6a, COP-Cl) is a superior catalyst because it does not require activation with silver salts and provides rearranged allylic trifluoroacetamides in good yields and high enantiomeric purities.     

手性二茂铁类配体在钯催化不对称反应中的应用

本文综述了近10 年来手性二茂铁类配体在钯催化不对称烯丙基取代反应,包括各种不同底物的烯丙基烷基化、烯丙基胺基化和烯丙基磺酰化反应中的应用,并对其在不对称Claisen 重排、不对称Diels-Alder 反应、不对称Heck 反应、不对称羰基化、不对称氢化硅烷化和不对称碳碳键断裂等反应中的应用进行了综述,对部分反应的机理和该领域的发展前景进行了讨论。     

手性烯丙基胺的合成进展

综述了近年来手性烯丙基胺的合成进展, 重点介绍了催化剂配体对化学选择性和对映选择性的影响, 并阐述了各种类型的反应机理.手性; 烯丙基胺; 催化     

Pd-catalyzed asymmetric allylic substitution reactions using P-chirogenic diaminophosphine oxides: DIAPHOXs

This paper describes the development of a new class of chiral phosphorus ligand: aspartic acid-derived P-chirogenic diaminophosphine oxides, DIAPHOXs, and their application to several Pd-catalyzed asymmetric allylic substitution reactions. Pd-catalyzed asymmetric allylic alkylation was initially examined in detail using diaminophosphine oxides 1a, resulting in the highly enantioselective construction of quaternary stereocenters. Mechanistic investigations revealed that 1a is activated by N,O-bis(trimethylsilyl)acetamide-induced tautomerization to afford a trivalent diamidophosphite species 12, which functions as the actual ligand. Furthermore, asymmetric allylic amination was examined using Pd-DIAPHOX catalyst systems, providing a variety of chiral allylic amines.     

The Asymmetric Aza‐Claisen Rearrangement: Development of Widely Applicable Pentaphenylferrocenyl Palladacycle Catalysts

Systematic studies have been performed to develop highly efficient catalysts for the asymmetric aza‐Claisen rearrangement of trihaloacetimidates. Herein, we describe the stepwise development of these catalyst systems involving four different catalyst generations finally resulting in the development of a planar chiral pentaphenylferrocenyl oxazoline palladacycle. This complex is more reactive and has a broader substrate tolerance than all previously known catalyst systems for asymmetric aza‐Claisen rearrangements. Our investigations also reveal that subtle changes can have a big impact on the activity. With the enhanced catalyst activity, the asymmetric aza‐Claisen rearrangement has a very broad scope: the methodology not only allows the formation of highly enantioenriched primary allylic amines, but also secondary and tertiary amines; allylic amines with N‐substituted quaternary stereocenters are conveniently accessible as well. The reaction conditions tolerate many important functional groups, thus providing stereoselective access to valuable functionalized building blocks, for example, for the synthesis of unnatural amino acids. Our results suggest that face‐selective olefin coordination is the enantioselectivity‐determining step, which is almost exclusively controlled by the element of planar chirality.     

Ligand‐Controlled Copper‐Catalyzed Highly Regioselective Difluoromethylation of Allylic Chlorides/Bromides and Propargyl Bromides

Highly regiodivergent copper‐catalyzed allylic/propargylic difluoromethylation reactions by employing different ligands are described. When 5,6‐dimethyl‐1,10‐phenanthroline was used as the ligand, exclusively α‐difluoromethylated products were obtained, while γ‐selective difluoromethylated products were generated when N‐heterocyclic carbene‐SIPr was used as the ligand. Likewise, high α‐ vs. γ‐selectivities were achieved in the presence of similar copper catalysts for the reactions of propargyl bromides. Moreover, a copper‐catalyzed asymmetric allylic difluoromethylation reaction with moderate to good enantioselectivity by the use of chiral ligands was developed.     

Copper‐Catalyzed Enantioselective Allyl–Allyl Coupling between Allylic Boronates and Phosphates with a Phenol/N‐Heterocyclic Carbene Chiral Ligand

Copper‐catalyzed enantioselective allyl–allyl coupling between allylboronates and either Z‐acyclic or cyclic allylic phosphates using a new chiral N‐heterocyclic carbene ligand, bearing a phenolic hydroxy, is reported. This reaction occurs with exceptional S_N2′‐type regioselectivities and high enantioselectivities to deliver chiral 1,5‐diene derivatives with a tertiary stereogenic center at the allylic/homoallylic position.     

Nickel(0)‐Catalyzed Hydroalkenylation of Imines with Styrene and Its Derivatives

A nickel(0)‐catalyzed hydroalkenylation of imines with styrene and its derivatives is described. A wide range of aromatic and aliphatic imines directly coupled with styrene and its derivatives, thus providing various synthetically useful allylic amines with up to 95 % yield. The reaction offers a new atom‐ and step‐economical approach to allylic amines by using alkenes instead of alkenyl‐metallic reagents. Experiments and DFT calculations showed that TsNH₂ promotes the proton transfer from the coordinated olefin to the imine, accompanied by a new C?C bond formation.     

Synthesis of nearly enantiopure allylic amines by aza-Claisen rearrangement of Z-configured allylic trifluoroacetimidates catalyzed by highly active ferrocenylbispalladacycles

The development of the first highly active enantioselective catalyst for the aza-Claisen rearrangement of Z-configured allylic trifluoroacetimidates generating valuable almost enantiopure protected allylic amines is described. Usually Z-configured allylic imidates react significantly slower than their E-configured counterparts, but in the present study the opposite effect was observed. Z-Configured olefins have the principal practical advantage that a geometrically pure C=C double bond can be readily obtained, for example, by semihydrogenations of alkynes. Our catalyst, a C(2)-symmetric planar chiral bispalladacycle complex, is rapidly prepared from ferrocene in four simple steps. Key step of this protocol is an unprecedented highly diastereoselective biscyclopalladation providing dimeric macrocyclic complexes of fascinating structure. In the present study as little as 0.1 mol % of catalyst precursor were sufficient for most of the alkyl substituted substrates to give in general almost quantitative yields. NMR investigations revealed a monomeric structure for the active catalyst species. The bispalladacycle can also be used for the formation of almost enantiomerically pure allylic amines (ee > or =96 %) substituted with important functional groups such as ester, ketone, ether, silyl ether, acetal or protected amino moieties providing high-added-value allylic amine building blocks in excellent yield (> or =94 %). The preparative advantages should render this methodology highly appealing as a practical and valuable tool for the formation of allylic amines in target oriented synthesis.     

Cooperative Catalysis by Palladium and a Chiral Phosphoric Acid: Enantioselective Amination of Racemic Allylic Alcohols

Cooperative catalysis by [Pd(dba)₂] and the chiral phosphoric acid BA1 in combination with the phosphoramidite ligand L8 enabled the efficient enantioselective amination of racemic allylic alcohols with a variety of functionalized amines. This catalytic protocol is highly regio‐ and stereoselective (up to e.r. 96:4) and furnishes valuable chiral amines in almost quantitative yield.     

Enantioselective Allylic Oxidation of Olefins Using Chiral Quinolinyl‐oxazoline Copper Complex Catalysts

Copper complexes of chiral quinolinyl‐oxazoline have been studied as the catalysts for enantioselective allylic oxidation of cycloalkenes with tert‐butyl perbenzoate. Using 5 mol% of these chiral catalysts, optical active allylic benzoates were obtained in moderate enantiomeric excesses. CuOTf prepared in situ, CuClO₄ and CuPF₆ were found to be good precatalysts in acetone.     

Pentacoordinated Carboxylate π‐Allyl Nickel Complexes as Key Intermediates for the Ni‐Catalyzed Direct Amination of Allylic Alcohols

Direct amination of allylic alcohols with primary and secondary amines catalyzed by a system made of [Ni(1,5‐cyclooctadiene)₂] and 1,1′‐bis(diphenylphosphino)ferrocene was effectively enhanced by adding nBu₄NOAc and molecular sieves, affording the corresponding allyl amines in high yield with high monoallylation selectivity for primary amines and high regioselectivity for monosubstituted allylic alcohols. Such remarkable additive effects of nBu₄NOAc were elucidated by isolating and characterizing some nickel complexes, manifesting the key role of a charge neutral pentacoordinated η³‐allyl acetate complex in the present system, in contrast to usual cationic tetracoordinated complexes earlier reported in allylic substitution reactions.     

Pseudo‐Stereodivergent Synthesis of Enantioenriched Tetrasubstituted Alkenes by Cascade 1,3‐Oxo‐Allylation/Cope Rearrangement

The catalytic diastereodivergent construction of stereoisomers having two or more stereogenic centers has been extensively studied. In contrast, the switchable introduction of another stereogenic element, that is, Z/E configuration involving a polysubstituted alkene group, into the optically active stereoisomers, has not been recognized yet. Disclosed here is the pseudo‐stereodivergent synthesis of highly enantioenriched tetrasubstituted alkene architectures from isatin‐based Morita–Baylis–Hillman carbonates and allylic derivatives, under the cooperative catalysis of a tertiary amine and a chiral iridium complex. The success of the switchable construction of the tetrasubstituted alkene motif relies on the diastereodivergent 1,3‐oxo‐allylation reaction between N‐allylic ylides and chiral π‐allyliridium complex intermediates by ligand and substrate control, followed by the stereoselective concerted 3,3‐Cope rearrangement process.     

Construction of Quaternary Stereogenic Carbon Centers through Copper‐Catalyzed Enantioselective Allylic Cross‐Coupling with Alkylboranes

A combination of an in situ generated chiral Cu^I/DTBM‐MeO‐BIPHEP catalyst system and EtOK enabled the enantioselective S_N2′‐type allylic cross‐coupling between alkylborane reagents and γ,γ‐disubstituted primary allyl chlorides with enantiocontrol at a useful level. The reaction generates a stereogenic quaternary carbon center having three sp³‐alkyl groups and a vinyl group. This protocol allowed the use of terminal alkenes as nucleophile precursors, thus representing a formal reductive allylic cross‐coupling of terminal alkenes. A reaction pathway involving addition/elimination of a neutral alkylcopper(I) species with the allyl chloride substrate is proposed.