Reissert asymmetric

Additions to quinoline derivatives also continued to be reported last year. Chiral dihydroquinoline-2-nitriles 55 were prepared in up to 91% ee via a catalytic, asymmetric Reissert-type reaction promoted by a Lewis acid-Lewis base bifunctional catalyst. The dihydroquinoline-2-nitrile derivatives can be converted to tetrahydroquinoline-2-carboxylates without any loss of enantiomeric purity <00JA6327>. In addition the cyanomethyl group was introduced selectively at the C2-position of quinoline derivatives by reaction of trimethylsilylacetonitrile with quinolinium methiodides in the presence of CsF <00JOC907>. The reaction of quinolylmethyl and l-(quinolyl)ethylacetates with dimethylmalonate anion in the presence of Pd(0) was reported. Products of nucleophilic substitution and elimination and reduction products were obtained . Pyridoquinolines were prepared in one step from quinolines and 6-substituted quinolines under Friedel-Crafts conditions <00JCS(P1)2898>. 

The polymer-bound catalyst was recyclable by filtration and showed just slightly decreased activity when reused. Catalyst (33) also promotes asymmetric Reissert-type reactions [106]. 

Shibasaki and co-workers applied (BINOL)Al(III)-derived catalyst 5a, previously developed for the cyanation of aldehydes [28], to the asymmetric Strecker reaction. This catalyst proved to be highly enantioselective for both aromatic and a,p-unsaturated acyclic aldimines (>86% ee for most substrates) (Scheme 8) [63-65]. Aliphatic aldimines underwent cyanide addition with lower levels of enantioselectivity (70-80% ee). A significant distinction of 5 relative to other catalysts is, undoubtedly, its successful application to the hydrocyanation of quinolines and isoquinolines, followed by in situ protection of the sensitive cx-amino nitrile formed (this variant of the Strecker reaction is also known as the Reissert reaction [66]). Thus, Shibasaki has shown that high enantioselectivities (>80% ee for most substrates) and good yields are generally obtainable in the Reissert reaction catalyzed by 5b [67,68]. When applied to 1-substituted... 

Rozwadowska and coworkers carried out the asymmetric alkylation of isoquino-line Reissert compounds under phase-transfer conditions using cinchonine-derived quaternary ammonium salts as catalysts. The best enantioselectivity was achieved in the benzylation and allylation of 1 -cyano-2-phenoxy carbonyl-1,2-dihydroisoquinoline (17) catalyzed by 2a (Scheme 2.14) [34]. 

In order to circumvent the problem of low yields in the usual Ullmann reaction, most syntheses of bisbenzylisoquinoline alkaloids have formed the diphenyl ether linkages at an early stage and confronted the problem of isomer separation later. In the case of phaeantharine (18) (Section II,A,3), which has no asymmetric carbons, this approach was clearly preferred. This synthesis exemplifies the use of Reissert alkylation as a key step (9,269). Several analogs of bisbenzylisoquinoline alkaloids were prepared in an analogous manner (270,271). One... 

A chiral auxiliary-mediated Reissert reaction has been demonstrated. Though the diastereomeric ratios are not as high as hoped, the conditions are simple and the products are easily separated by flash chromatography (Equation 63) <2005TL2983>. A catalytic version of the asymmetric Reissert reaction with quinolines, isoquinolines, and pyridines has been developed by Shibasaki and co-workers <2005PAC2047, 2004JA11808>. 

Abstract The chapter reviews the classic Reissert reaction, the keystone of a broad family of multicomponent reactions involving azines, electrophilic reagents and nucleophiles to yield A,a-disubstituted dihydroazine adducts. The first sections deal with the standard nucleophilic attack upon activated azines, including asymmetric transformations. Section 5 focuses on the generation of dipolar intermediates by azine activation, and on their subsequent transformation chiefly in cycloadditions. Lastly, Sect. 6 is primarily devoted to a special branch of this chemistry involving isocyanides. It also covers the reactivity of dihydroazines and reviews the mechanistic proposals for related reactions. 

This account reviews recent advances in Reissert-type transformations, focusing on the use of different reactants, asymmetric versions of the process, and also on dipole-related reactivity and on the participation of activated azines in isocyanide-MCRs. 

FMOC-protected amino acid fluorides afford the expected Reissert adducts 160 with a good stereoselectivities, the a-sulfonylamino acid fluorides undergo cycliza-tion to adduct 161 [47, 140, 141], Itho s protocol is amenable to using silyl enol ethers 157 as nucleophiles [142], Gibson has used bulky asymmetric acid chlorides as substrates in a Reissert reaction with TMS-CN the corresponding Reissert compound was then treated with aldehydes and sodium hydride to obtain the enantiopure adducts 4 (Scheme 3) [143],... 

Asymmetric two-center catalytic Reissert-type reactions 02CC1989. 

Asymmetric acylcyanation of quinolines (Reissert-type reaction) with 2-furoyl chloride and TMSCN is successfully performed by using the chiral catalyst 168 (Scheme 10.243) [658]. In this reaction the sterically more demanding complex 168b exceeds 168a in enantioselectivity. 

Catalysts (25) are the Lewis acid-Lewis base bifunctional catalysts in which Lewis acid-Al(III) moiety activates acyl iminium ion and the Lewis base (oxygen of phosphine oxide) does TMSCN, simultaneously (Scheme 5.7). Halogen atoms at the 6-position enhanced both yields and enantioselectivity in Reissert-type cyanation of the imino part of 26. However, the order for the activation is not parallel to the electronegativity of the halogen atoms and, moreover, the strong electron-withdrawing trifluoromethyl group provided unexpectedly the worst result for the activation [13]. It is not simple to explain this phenomenon only in terms of the increased Lewis acidity of the metal center. Trifluoromethylated BINOL-zirconium catalysts (28) for asymmetric hetero Diels-Alder reaction (Scheme 5.8) [14], trifluoromethylated arylphosphine-palladium catalyst (32) for asymmetric hydrosilylation (Scheme 5.9) [15], and fluorinated BINOL-zinc catalyst (35) for asymmetric phenylation (Scheme 5.10) [16] are known. 

Cyanadons. Aluminum complexes of BINOLs (1) that are armed at C-3 and C-3 with diarylphosphine oxide groups possess both Lewis acid and base centers. Asymmetric cyanation of aldehydes and mines with MeaSiCN, and of quinolines and isoquinolines in a manner analogous to the Reissert reaction is successful (ee 70-90%). The asymmetric Strecker synthesis is applicable to conjugated aldimines and the higher reactivity of Me SiCN than HCN in the presence of 10 mol% of PhOH enables its use in catalytic amount while supplying stoichiometric HCN as the cyanide source. 

Elaboration of isoquinoline derivatives in asymmetric fashion was examined as well in 2001. In a manner similar to that described in section 6.1.3.2, an enantioselective Reissert-type reaction was utilized to construct a chiral, quaternary center at the Cl position of isoquinoline derivatives. For example, treatment of isoquinoline 85 with vinyl chloroformate and TMSCN in the presence of bifunctional catalyst 86 afforded isoquinoline derivatives such as 87 in up to 95% ee. The effect of the R group at the 1-position and the catalyst counterion were detailed. 

Lewis acid-base bifunctional asymmetric catalysis, particularly, in the Reissert reaction 05SL1491. 

Exanqrle 4, Asymmetric organocatalytic allylic alkylation of Reissert compounds ... 

Scheme 19.52 Asymmetric Reissert-type reactions of isoquinolines catalysed by a bifunctional Al-BINOL derivative.

Scheme 19.53 Asymmetric Reissert-type reactions of pyridine derivatives catalysed by Al-BINOL derivatives.

Shibasaki and coworkers developed a bifunctional chiral catalyst possessing the Lewis acid (aluminum metal) and the Lewis base (phosphine oxide), which was successfully applied to asymmetric Reissert-type reaction of trimethylsilylcyanide (TMSCN) [45]. The reaction of quinoline (92) with TMSCN and 2-furoyl chloride in the presence of Lewis acid Lewis base catalyst (91) occurred to give the Reisser product in 91% yield and 85% ee. The chiral catalyst was connected to JandaJRL... 

Enantioselective Reissert reaction using an Al-containing asymmetric bifunctional catalyst has been developed (eq 33). The Reissert reaction catalyzed by an Al-containing chiral catalyst can be used to enantioselectively construct a quaternary stereocenter (eq 34). ... 

Abstract The use of organoaluminum-based Lewis acids (A1R X3 R = alkyl, alkynyl, X = halide or pseudohalide) in the period 2000 to mid-2011 is overviewed with a focus on (1) stoichiometric reactions in which one of the organoaluminum substituents is transferred to the substrate (e.g., the opening of epoxides, 1,2-additions to carbonyl compounds, coupling with C-X, and Reissert chemistry) and (2) asymmetric, often catalytic, reactions promoted by Lewis acid catalysts derived from organoaluminum species (e.g., use of auxiliaries with alanes, Diels-Alder, and related cycloaddition reactions, additions to aldehydes and ketones, and skeletal rearrangement reactions). 

Recently, Shibasaki and coworkers reported catalytic asymmetric Reissert reaction with chiral aluminum Lewis acid [66]. In the presence of Lewis acid-Lewis base bifunctional catalyst (R)-(64c) (9 mol%), the reaction of quinoline with TMSCN and... 

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