Radical reduction of Passerini 3CR adducts by SmI2/HMPA

The Passerini 3-CR adducts of substituted cinnamaldehydes,isocyanides and acetic acid were treated with SmI₂/HMPA in dry tetrahydrofuran（THF） at room temperature,andβ,γ-unsaturated amides were obtained in moderate yields.The reaction was supposed involving a radical reduction procedure.     

Passerini多组分反应研究进展

多组分反应操作简便、原子经济性高,是一类重要的有机反应。经典Passerini反应是以异腈、醛酮、羧酸为原料一步合成α-酰氧基酰胺的多组分反应,其产物作为重要的有机中间体,可以进一步合成许多重要的药物、天然产物和功能材料等复杂有机分子,具有广泛的应用价值。本文从反应底物、串联反应及相关应用的角度阐述近5年来Passerini多组分反应研究的新进展。     

An intramolecular Tsuji-Trost reaction based approach to the synthesis of 6-methylene indolizidines

Herein we describe the efficient stereoselective preparation of C8 substituted indolizidines bearing a 6-methylene group, from the chiral pool starting material l-proline. This synthesis, employing a Tsuji-Trost reaction as the key step, represents a potentially, efficient route to pumiliotoxin natural product epimers.     

Fully regio- and endo-stereoselective synthesis of new polycyclic allylic sulfides via a Diels-Alder reaction. Synthetically useful transformations of these sulfides

Thermal and Lewis acid catalyzed cycloadditions of (Z)-1,2-diheterosubstituted-1,3-dienes to a variety of dienophiles are described. Both endo/exo and regioselectivity have been investigated. In all cases cycloaddition reactions exhibited full regio- and endo-stereoselectivity. The obtained cycloadducts are new polycyclic allylic sulfides carrying much structural and stereochemical informations. Work on transformation of the adducts, mainly to the corresponding new 1,3-dienes and aromatic compounds, is also presented.     

Diastereoselective Passerini reactions using p-toluenesulfonylmethyl isocyanide (TosMIC) as the isonitrile component

p-Toluenesulfonylmethyl isocyanide (TosMIC) is used for the first time as the isonitrile component in a diastereoselective Passerini reaction with sugar-derived aldehydes to afford products in moderate to good yields (40-90%) and selectivities (30-90% de’s).     

New access to fluorinated ketoglycolic acid derivatives from trifluoropyruvamides

Hydrates of trifluoropyruvamides are readily obtained from isocyanides and trifluoroacetic anhydride. Under catalysis with secondary amines, these hydrates were successfully reacted with various methylketones to form fluorinated aldol type compounds. The effect of the amine is discussed as well as Henry type additions with nitromethane.     

Metathesis at an Implausible Site: A Formal Total Synthesis of Rhizoxin D

The new approach to the anticancer agent rhizoxin D described herein does not cohere with the conventional logic of metathesis, according to which macrocycles are best closed at a disubstituted olefinic site; rather, the trisubstituted C11?C12 alkene flanked by an allylic ‐OH group served as the pivot point for synthesis. This motif was attained in good yield and excellent selectivity by a sequence of alkyne metathesis, trans‐hydrostannation and cross coupling. Because the exact same substructure is prominently featured in numerous other natural products, the underpinning strategy, though unusual, might bear more general relevance.     

Intramolecular Diels-Alder reaction leading to tricyclic derivatives as intermediates of natural products synthesis

Tricyclic compounds 4a and 4b possessing a bicyclo[4.3.0] moiety, were successfully synthesized by using the intramolecular Diels-Alder reaction. The siloxy- rather than acyloxy-substituents increased the ratio of the endo-cylcoadducts 10 and 12. The oxygen substitution of 9 influenced conformation of the transition state, which was stereochemically restricted by the butenolide moiety. In addition, 9b carrying a hydroxyl group also produced 10b in a similar ratio to 9a. Compound 11 was the only exo-adduct produced in all of the entries.     

Pd-catalyzed halocyclizations of unactivated 1,6-diynes through a formal anti-carbopalladation/bromide radical cascade

We report a Pd-catalyzed halocyclization of unactivated 1,6-diynes with N-bromosuccinimide (NBS). This approach produces stereo-defined dibromo substituted dihydropyrans, tetrahydropyridines, and 3-methylene cyclohexenes with exocyclic double bond appendages in mostly good yields. Copper salt was found to be a useful Lewis acid in this reaction. Mechanistically, a formal anti-carbopalladation and a bromide radical promoted Pd^II-Pd^III-Pd^I-Pd^II catalytic cycles were proposed to be involved in the formation of the dibromo-substituted products. Further functionalization of the dihydropyran derivatives underwent B(C₆F₅)₃-catalyzed ring opening, and reduction afforded dibrominated 1,3-dienes with excellent stereoselectivity.     

Cycloaddition of a 1,2-diaza-1,3-butadiene to phenylpropiolic acid: an efficient route to pyridazinoquinolone derivatives

Diazocoupling of dihydroquinolin-4-ones with aryldiazonium nitrates gave the corresponding diazo derivatives, which undergo facile (4+2) cycloaddition reactions with phenylpropiolic acid to afford 2-aryl-4a-methyl-10-oxo-4-phenyl-2,4a,5,10-tetrahydropyridazino[4,3-b]quinoline-3-carboxylic acid derivatives 3. However, with β-nitrostyrene a mixture of three isomeric products 4a-c was obtained.     

Concise Synthesis of Acetal-Protected syn 1,3-Diols by a Tandem Hemiacetal Formation/Tsuji-Trost Reaction

Designed, developed, and applied: A novel domino sequence was used for the rapid assembly of acetal-protected syn 1,3-diols. The convergent synthesis of a polyol fragment of the macrolide antibiotic RK-397 demonstrates that this method is suitable for the rapid and stereoselective preparation of polyketide-type diol motifs.     

Manipulating the enone moiety of levoglucosenone: 1,3-Transposition reactions including ones leading to isolevoglucosenone

The manipulation of the enone moiety associated with the biomass-derived, homochiral and now abundant compound levoglucosenone (1) is described. While the trichloroacetimidates derived from the allylic alcohols 3 and 4 failed to engage in Overman-type rearrangements, certain ester derivatives reacted in the presence of Pd[0]-catalysts to give regio-isomeric mixtures of β,γ-unsaturated malonates or ketones, the structures of which were confirmed by single-crystal X-ray analyses. In other sequences involving 1,3-transposition reactions, an operationally simple means for converting compound 1 into isolevoglucosenone (2) is described.

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Easy access to N-aryl, N-heteroarylbenzoxazolinones and 4-aza analogues via Diels-Alder cycloaddition reactions

An improved method for the synthesis of N-aryl, N-heteroarylbenzoxazolinones and their 4-aza analogues is described. The process involves the Diels-Alder cycloaddition of benzoxazinic or pyridoxazinic dienic systems with dienophiles as a key step.     

A One‐Pot O‐Phosphinative Passerini/Pudovik Reaction: Efficient Synthesis of Highly Functionalized α‐(Phosphinyloxy)amide Derivatives

A one‐pot O‐phosphinative Passerini/Pudovik reaction has been developed, based on reacting aldehydes, isocyanides, and phosphinic acids followed by the addition of second aldehydes to form the corresponding α‐(phosphinyloxy)amide derivatives. This is the first reported instance of a Passerini‐type, isocyanide‐based multicomponent reaction using a phosphinic acid instead of a carboxylic acid. The nucleophilicity of the phosphinate group allows a subsequent catalytic Pudovik‐type reaction, affording the highly functionalized α‐(phosphinyloxy)amide derivative in high yield. A wide range of aldehydes and isocyanides are applicable to this reaction.     

An efficient preparation of N-per- (or poly)fluorophenyl pyrroles and N-fluoroalkanesulfonyl pyrroles

Hetero-Diels-Alder reaction of N-sulfinyl per- (or poly)fluoroaniline and N-sulfinylfluoroalkanesulfonyl amine with 1,3-dienes affords the corresponding cycloadduct 3,6-dihydro-1,2-thiazine-1-oxide which is readily converted to N-per- (or poly)fluorophenyl pyrrole and N-fluoroalkanesulfonyl pyrrole under mild reaction conditions in good yields.     

Studies on the application of the Passerini reaction and enzymatic procedures to the synthesis of tripeptide mimetics

A new, efficient method for the multicomponent synthesis of tripeptide mimetics is presented. Simple, chemoenzymatic transformations of Passerini reaction products enable the introduction of varied amino acid moieties into the tripeptide scaffold, with control of the stereochemistry. Additionally, this method allows the convenient introduction of a methyl group to the amide nitrogen, leading to derivatives of N-methylated amino acids—compounds of interest for medicinal chemistry.     

A furan ring expansion approach to the synthesis of novel pyridazino-psoralen derivatives

A convenient preparation of the parent tetrahydrobenzodifuran 2 was developed from resorcinol. The oxidation of one or both furan rings of this key intermediate was accomplished with DDQ and the resulting benzodifuran was subsequently reacted with 3,6-dimethoxycarbonyl-1,2,4,5-tetrazine to afford the expected pyridazino-psoralen derivative in good yield. This simple method allowed the efficient preparation of a pyridazino-psoralen derivative with a formyl group at C-7, which was introduced by directed ortho-lithiation in the intermediate 2. An aminoalkyl side-chain was also introduced to the tetracyclic skeleton through the aldehyde functionality in a reductive amination process, which was accompanied by an unprecedented reduction of the pyridazine ring.     

A facile method for the stereoselective preparation of (1E,3E)-4-substituted-1-amino-1,3-dienes via 1,4-elimination

The 1,4-elimination reaction of 1-amino-4-methoxy-(2Z)-alkenes is shown to proceed with high (1E,3E)-stereoselectivities to afford the corresponding 4-substituted-1-amino-1,3-dienes in good yield. The scope and stereochemical features of the synthetic method are described.