Direct cross-coupling between N-methyltetrahydroisoquinolines and alkynes using CuI-DEAD is presented. It affords the regioselective C-1-alkynylated products in good yield. This regioselectivity is in contrast to the results reported earlier in the reaction of N,N-dimethylbenzyl amine where the N-methyl alkynylated product was formed exclusively or predominantly. The C-1-substituted propargylic isoquinolines were easily reduced to phenethylisoquinolines with Pd/C. This reaction sequence provides a short route to synthesize methopholine, homolaudanosine and other phenethylisoquinoline alkaloids.
2S)-2-[(Phenylsulfinyl)methyl]pyrrolidine, derived from L-proline, has been demonstrated as an efficient organocatalyst for the asymmetric Michael addition of cyclohexanone and cyclopentanone to β-nitrostyrenes. This pyrrolidine-based catalyst bearing a sulfoxide moiety was used to synthesize various γ-nitro carbonyl compounds in high yield (up to 97%) with excellent stereoselectivity (up to >99:1 dr and >99% ee) without the use of any additive.Organocatalysis with its asymmetric variant has emerged as a powerful synthetic paradigm for the development of new methods to prepare diverse chiral molecules. 1 Organocatalytic conjugate addition is an important and widely applicable strategy for asymmetric carbon-carbon bond formation using a variety of donors and acceptors. 2 In recent years, several catalysts have been developed for the direct asymmetric Michael addition of unmodified carbonyl compounds to nitroalkenes to produce enantiomerically enriched γ-nitro ketones. 3 Many of these are pyrrolidine-based organocatalysts having different functionalities in the side chain. 4 Some examples of pyrrolidine-type organocatalysts bearing a sulfide/sulfone 5a or sulfonamide 5b function in the side chain have also been reported for the above reactions. An oxygen atom of the sulfone functionality in combination with a protic solvent, such as water, provides a hydrogen-bond interaction to improve both the reactivity and stereoselectivity of the Michael reaction. 5 β-Amino sulfoxides have been used as effective bidentate ligands in metal-catalyzed enantioselective reactions and have also served as chiral auxiliaries in various processes promoted by transition metals; 6 however, the use of β-amino sulfoxides as chiral organocatalysts does not seem to have been investigated so far. As part of our interest in the development of new pyrrolidinebased organocatalysts 7a and continuing our investigations toward the stabilization of α-amino sulfoxides, 7b we explored the use of β-amino sulfoxide 1 as a chiral catalyst in asymmetric Michael additions. Interestingly, this catalyst proved very successful for the stereoselective conjugate addition of cyclic ketones to various aryl-substituted nitroolefins and afforded the corresponding adducts in high yield (up to 97%) with excellent stereoselectivity (up to >99:1 dr and >99% ee) in wet toluene. The results are described in this paper. The chiral catalyst (2S)-2-[(phenylsulfinyl)methyl]pyrrolidine (1) employed in this work was easily prepared, according to Scheme 1. Reduction of Boc-protected Lproline 2 with borane-methyl sulfide complex (BMS) afforded the corresponding alcohol 3 in 92% yield. 8 Reaction of this alcohol 3 with p-toluenesulfonyl chloride 8 and subsequent treatment with sodium hydride and benzenethiol gave thioether 5. 5a Oxidation of 5 with sodium periodate in methanol-water (1:1) 9 and then deprotection 5a with trifluoroacetic acid furnished the catalyst 1 in 57% overall yield.
Scheme 1 Synthesis of catalyst 1For initial studies, the reaction of cyclohexanone (7a) and β...
A novel approach for the direct C-4 arylation of N-methyl-1,2,3,4-tetrahydroisoquinolines by nucleophilic addition of β-aminocarbanions to benzynes is described which provides a one-pot procedure for synthesis of the title compounds.
A simple protocol for the C1 arylation of tetrahydroisoquinolines with aryl Grignard reagents via diethyl azodicarboxylate (DEAD) mediated oxidative C-H activation under metal-free conditions has been developed. The target compounds, including some naturally occurring alkaloids, were obtained in moderate to good yields.
The development of greener and atom economical methods for carbon-heteroatom (CÀ Het) bond formation is of significant importance in synthetic organic chemistry. In this regard, metal-free cross-dehydrogenative coupling (CDC) represents an attractive approach as it is more facile and environment friendly. This review intends to focus on the recent developments in metal-free CDC reactions for CÀ Het bond formation leading to the synthesis
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