Masked Aldehydes Research Articles

Electrochemical-induced radical allylation via the fragmentation of alkyl 1,4-dihydropyridines

Aldehydes are abundant chemical motifs presented in natural products and pharmaceuticals. As a radical precursor, its application is limited. Dihydropyridines (DHPs) can act as masked aldehydes, providing alkyl radicals under the activation of Lewis acid, heat, SET oxidant and light irradiation. Herein, we report the direct activation of 4-alkyl DHPs via single electron transfer at the anode. CC bond homolysis at the C4-position of DHP generated the corresponding alkyl radical, which was captured subsequently by 2-phenyl and 2-ethoxy carbonyl allyl bromide. The following intramolecular elimination reaction afforded 20 different radical allylation products bearing various alkyl substituents with yields up to 92%.

Electrochemical cascade synthesis of α-thio-substituted masked aldehydes

An unprecedented 3-component cascade synthesis of β,β-dialkoxy sulfides under mild electrochemical conditions has been achieved.

Easy access to elusive radical reactions.

Two mild approaches generate radical intermediates from masked aldehydes

(−)-8-Amino menthol-derived perhydrobenzoxazines as chiral templates and masked aldehydes in the diastereoselective intermolecular Pauson–Khand reaction

Perhydro-1,3-benzoxazines derived from (−)-8-amino menthol behave as masked aldehydes and chiral templates in diastereoselective intramolecular Pauson–Khand reactions with norbornene and norbornadiene. The regioselectivity is excellent for unsubstituted or methyl-substituted acetylenes and moderate with phenyl-substituted alkynes. The stereoselection is very poor or moderate depending also on the substitution pattern of both the triple bond and the perhydrobenzoxazine nucleus. The hydrolysis of the cycloadducts leads to 2- or 3-formyl–cyclopentenone derivatives.

ChemInform Abstract: Exploration of the Interrupted Fischer Indolization Reaction.

AbstractCondensation of various aromatic hydrazines with masked aldehydes, i.e.

Synthesis of Masked Vicinal Amino Aldehydes of Pyrrolizine and Pyrrolo [1,2-c]thiazole Series

Acylation of (1,3-dihydro-1,3-dimethyl-2 H-benzimidazol-2-ylidene)acetonitrilewith mixed anhydrides of N-Boc proline and4-thiazolidinecarboxylic acid was found to proceed at the exocycliccarbon atom yielding the corresponding C-acylderivatives. Removal of the protecting group with equimolar amountof hydrochloric acid effected simultaneous cyclization affording2-(3-amino-5,6,7,7a-tetrahydro-1-oxo-1 H-pyrrolizin-2-yl)-and 2-(5-amino-7,7a-dihydro-7-oxo-1 H,3 H-pyrrolo[1,2- C]thiazol-6-yl)-1,3-dimeth-ylbenzimidazoliumchlorides. Reduction of the prepared salts with sodium borohydrideresulted in 3-amino-2-(2,3-dihydro-1,3-di-methyl-1 H-benzimidazol-2-yl)-5,6,7,7a-tetrahydro-1 H-pyrrolizin-1-one and 5-amino-6-(2,3-dihydro-1,3-dimethyl-1 H-benzimidazol-2-yl)-1,7a-dihydro-3 H,7 H-pyrrolo[1,2- C]thiazol-7-one, respectively. Thesecompounds were shown to be masked aldehydes. Their reactions withphenylhydrazine and hydroxylamine yielded corresponding hydrazonesand oximes, whereas condensation with malononitrile furnished 2-amino-5a,6,7,8-tetrahydro-5-oxo-5 H-pyrido[3,2- B]pyrrolizine-3-carbonitrileand 2-amino-5a,6-dihydro-5 H,8 H-thiazolo[3′,4′:1,5]pyrrolo[2,3- B]pyridine-3-carbonitrile.

Enantiomerically pure α-methoxyaryl acetaldehydes as versatile precursors: a facile chemo-enzymatic methodology for their preparation

A facile and efficient synthesis of optically active α-methoxyaryl acetic acids (up to 95% ee), α-methoxyaryl ethanols (up to 93% ee) and α-methoxyaryl acetonitriles (up to 93% ee) was achieved via Arthrobacter sp . lipase-catalyzed kinetic resolution of masked aldehydes as the key synthons, that is, α-hydroxyaryl acetaldehyde acetals.

Solid‐Phase Synthesis of Tetrahydro‐β‐carbolines and Tetrahydroisoquinolines by Stereoselective Intramolecular N‐Carbamyliminium Pictet–Spengler Reactions

A solid-phase method for the synthesis of tri-, tetra-, and pentacyclic compounds containing tetrahydro-beta-carboline, tetrahydroisoquinoline or analogous scaffolds is presented. The reaction proceeds with high stereoselectivity through an intermediate N-carbamyliminium ion that exclusively converts into Pictet-Spengler-type products with a variety of C-nucleophiles. Amino aldehydes masked with 3-Boc-(1,3)-oxazinane (Box) have been synthesized from amino acids, amino alcohols, or 2-nitro benzaldehydes. The amino moiety of these masked aldehydes has been converted into pentafluorophenyl carbamate to serve as a urea precursor. The building blocks were incorporated at the N-terminal of a resin-supported dipeptide through urea formation. Subsequent treatment with acid liberated the aldehyde quantitatively. A penultimate tryptophan residue gave rise, under the acetic conditions, to a spontaneous intramolecular Pictet-Spengler reaction with the liberated aldehyde. The reaction proceeded with a high degree of stereoselectivity affording tetrahydro-beta-carbolines with a de (de=diastereomeric excess) above 95 % and purity in the range of 90-99 %. This reaction has been extended to a range of other aromatic C-nucleophiles, including substituted indoles, benzenes, pyrene, furan, thiophenes, and benzothiophene with comparable stereoselectivity and purity. Prolonged exposure of the benzaldehyde-derived Pictet-Spengler products to strong acid and air lead to quantitative auto-oxidation which yielded compounds with a 3,4-dihydro-beta-carboline, a 3,4-dihydroisoquinoline, or a similar core structure.

Addition of Aldehydes and Their Equivalents to Electron‐Deficient Alkenes Using N‐Hydroxyphthalimide (NHPI) as a Polarity‐Reversal Catalyst.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Addition of aldehydes and their equivalents to electron-deficient alkenes using N-hydroxyphthalimide (NHPI) as a polarity-reversal catalyst

Radical addition of aldehydes and masked aldehydes like 1,3-dioxolanes to electron-deficient alkenes was achieved by the use of catalytic amounts of BPO and N-hydroxyphthalimide (NHPI) as a polarity-reversal catalyst under mild conditions. Three-component radical coupling of 1,3-dioxolanes, maleates, and alkenes was performed in the presence of BPO and NHPI under similar conditions.

Stereochemical control in the preparation of α-amino N-methylthiazolidine masked aldehydes used for peptide aldehydes synthesis

Chiral N-methyl thiazolidines masked α-amino aldehydes are used for solid phase peptide aldehyde elongation. Contrary to N-Boc-protected α-amino aldehydes, N-trityl protection secures the chiral integrity of the incoming aldehyde chiral C1′ carbon atom during condensation of the amino aldehydes with l-cysteinyl residues. The Ac-Tyr-Val-Ala-Asp-H caspase inhibitor was prepared on a solid support starting from the N-trityl-amino thiazolidine masked aspartinal as a validation of this process.

Clavines as antitumor agents; 2. Natural 8-hydroxymethyl-ergoline type clavines and their derivatives.

The cytostatic potentials of 16 clavines were determined in the L5178y mouse lymphoma cell system: three of them are natural 8-hydroxymethylergoline type alkaloids (elymoclavine, lysergol, dihydrolysergol-I) and 13 are semisynthetic derivatives ( O-acyl-; 1-alkyl-; 1-alkyl- O-acyl-; 1, O-dialkyl-; masked aldehydes). It is shown that in contrast to these alkaloids some of their derivatives are potent cytostatic agents: 1-propylelymoclavine (ED 50 cone.: 2.2 μM), 1-propylelymoclavine- O-butyrate (2.7 μM), 6-methyl-8β-(2′-oxo-cyclohexylidenemethyl)-ergoline-I (4.0 μM). O-Acyl derivatives without substitution at N-1 were almost inactive. The substitution of the hydrogen at N-1 of inactive clavines by an alkyl group with three carbon atoms led to very active compounds indicating that the nature of the substituent at N-1 is very important for cytostatic activity. Incorporation studies in the presence of 1-propylelymoclavine showed that this compound inhibits primarily DNA synthesis. Partial syntheses of new ergolines are described.