Azo anions in synthesis : Use of trityl- and diphenyl-4-pyridylmethylhydrazones for reductive C-C bond formation

The lithium salts of trityl- and diphenyl-4-pyridylmethyl-hydrazones of both aldehydes and ketones react with electrophiles (alkyl halides, aldehydes, ketones, crotonates) at low temperature to form C-trapped azo compounds ; these Intermediates decompose homolytically with loss of nitrogen below room temperature and can be diverted in a synthetically useful way to alkanes, alkenes, alcohols or saturated esters.     

Allylic alcohols as radical allylating agents. An overall olefination of aldehydes and ketones

2-Fluoropyridyl derivatives of allylic alcohols react with xanthates in the presence of lauroyl peroxide to give alkenes, often with high stereoselectivity. If the allylic alcohols are themselves derived from aldehydes or ketones, the overall process becomes a synthetic equivalent of the classical Wittig and related olefination reactions.     

Carbopalladation of nitriles: synthesis of 2,3-diarylindenones and polycyclic aromatic ketones by the Pd-catalyzed annulation of alkynes and bicyclic alkenes by 2-iodoarenenitriles

2-iodobenzonitrile, its derivatives, and various heterocyclic analogues undergo palladium(0)-catalyzed annulation onto diarylacetylenes or bicyclic alkenes to afford 2,3-diarylindenones and polycyclic aromatic ketones in very good to excellent yields. This reaction represents one of the first examples of the addition of an organopalladium moiety to the carbon-nitrogen triple bond of a nitrile. The reaction is compatible with a number of functional groups. A reaction mechanism, as well as a model accounting for the electronic effects of substituents on the aromatic ring of the nitrile, is proposed.     

Highly reactive metals from potassium—graphite. Preparation and use of titanium—graphite and tin—graphite

The potassium—graphite route to active forms of metals has been extended to the preparation of titanium—graphite (Ti---Gr) and tin—graphite (Sn---Gr). The Ti---Gr is used to achieve the reductive coupling of ketones to give alkenes, and Sn---Gr is used in the preparation of diallyltin dibromide complexes which react with aldehydes to give homoallylic alcohols.     

Utilization of microwave heating in the McMurry reaction for facile coupling of aldehydes and ketones to give alkenes

Microwave heating was applied in high-yield syntheses of alkenes by McMurry coupling of aldehydes and ketones with low-valent titanium. All aldehydes and ketones including sulfur end-capped analogues gave alkenes in isolated yields above 80% without detectable amounts of pinacols.     

Asymmetric lithiation-substitution sequences of substituted allylamines

[reaction: see text] (-)-Sparteine-mediated asymmetric lithiation-substitution sequences of 2- and 3-substituted N-(Boc)-N-(p-methoxyphenyl) allylic amines with electrophiles have been investigated. Asymmetric lithiation-substitutions of N-(Boc)-N-(p-methoxyphenyl) allylic amines 11, 12, 13, 14, and 15 provide highly enantioenriched enecarbamates in good yields. Further transformations to give aldehydes, acids, ketones, and a Diels-Alder adduct are reported. The 1,4-addition products from reactions of the lithiated allylic amines from 14 and 15 with conjugated activated alkenes gives enecarbamates with two and three stereogenic centers in good yields with high diastereomeric and enantiomeric ratios. Synthetic transformation of these products by acid hydrolysis and subsequent cyclization provide stereoselective access to bicyclic compounds containing four and five stereogenic centers with high diastereoselectivity and enantioselectivity. It is suggested that allyllithium complexes generated by asymmetric deprotonation react with most electrophiles with inversion of configuration.     

Highly regio- and stereoselective ruthenium(II)-catalyzed direct ortho-alkenylation of aromatic and heteroaromatic aldehydes with activated alkenes under open atmosphere

Various aromatic and heteroaromatic aldehydes reacted with activated alkenes in the presence of a catalytic amount of [{RuCl(2)(p-cymene)}(2)], AgSbF(6), and Cu(OAc)(2)·H(2)O to give substituted alkene derivatives in a highly regio- and stereoselective manner. The corresponding alkene derivatives were further converted into unusual four-membered cyclic ketones or a polycyclic isochromanone derivative via a photochemical rearrangement. Notably, the catalytic reaction was conducted under an open atmosphere.     

Development of domino processes by using 7-silylcycloheptatrienes and its analogues

7-Silyl- and 7-silylmethylcycloheptatrienes were shown to react with acylnitroso reagents at room temperature, through their norcaradiene forms, to generate the corresponding cycloadducts 5?a-b and 6?a-b as single diastereomers. The course of the reaction was dramatically modified by changing the reaction conditions. Using a polar medium, functionalized cyclohexa-1,3-dienes 7?a-b and bicyclic compounds 13?a-b were instead generated, incorporating one or two amino groups. Similar behavior was observed by using other dienophiles, including triazolinedione, but also activated aldehydes and ketones. A tentative mechanism has been proposed to rationalize the formation of both classes of products that relies on a domino process involving four consecutive elementary steps, in this order: 1)?electrocyclic process, 2)?hetero-Diels-Alder reaction, 3)?cyclopropane ring opening, and 4)?hetero-Diels-Alder reaction. Trapping of the cationic intermediate and isolation of the primary cycloadduct provide support for this hypothesis. An enantioselective version of the cascade using cycloheptatriene 4?b and aldehydes and ketones, under copper(II) catalysis was also carried out, leading to cyclohexa-1,3-dienes 21, 28, and 30 with enantioselectivities up to 93?% ee. Finally, elaboration of the intermediates above has been carried out, opening a straightforward access to sugar mimics 42-43 and complex polycyclic systems 36 and 39.     

Development of Domino Processes by Using 7‐Silylcycloheptatrienes and Its Analogues

7‐Silyl‐ and 7‐silylmethylcycloheptatrienes were shown to react with acylnitroso reagents at room temperature, through their norcaradiene forms, to generate the corresponding cycloadducts 5 a – b and 6 a – b as single diastereomers. The course of the reaction was dramatically modified by changing the reaction conditions. Using a polar medium, functionalized cyclohexa‐1,3‐dienes 7 a – b and bicyclic compounds 13 a – b were instead generated, incorporating one or two amino groups. Similar behavior was observed by using other dienophiles, including triazolinedione, but also activated aldehydes and ketones. A tentative mechanism has been proposed to rationalize the formation of both classes of products that relies on a domino process involving four consecutive elementary steps, in this order: 1) electrocyclic process, 2) hetero‐Diels–Alder reaction, 3) cyclopropane ring opening, and 4) hetero‐Diels–Alder reaction. Trapping of the cationic intermediate and isolation of the primary cycloadduct provide support for this hypothesis. An enantioselective version of the cascade using cycloheptatriene 4 b and aldehydes and ketones, under copper(II) catalysis was also carried out, leading to cyclohexa‐1,3‐dienes 21 , 28 , and 30 with enantioselectivities up to 93 % ee. Finally, elaboration of the intermediates above has been carried out, opening a straightforward access to sugar mimics 42 – 43 and complex polycyclic systems 36 and 39 .     

Thermal cycloaddition of carbonyl compounds to a stable cyclobutadiene

In contrast to acid chlorides which undergo addition to 1 to form cyclobutene derivatives 4, aldehydes react with the same antiaromatic starting compound 1 to give the [4+2]-cycloaddition product 5. Activated ketones such as 1,1,1-trifluoroacetone, biacetyl, and acetyl cyanide undergo a clean cycloaddition reaction to tricyclic compounds (1 + 6a?c → 9a?c), whereas trioxoindane yields a bicyclic product (1 + 6d → 8d).     

Stereochemistry of the allylation and crotylation reactions of alpha-methyl-beta-hydroxy aldehydes with allyl- and crotyltrifluorosilanes. Synthesis of anti,anti-dipropionate stereotriads and stereodivergent pathways for the reactions with 2,3-anti- and 2,3-syn-alpha-methyl-beta-hydroxy aldehydes

A new method for the stereoselective synthesis of the anti,anti-dipropionate stereotriad via the reaction of alpha-methyl-beta-hydroxy aldehydes with (Z)-crotyltrifluorosilane (24) is described. These reactions were designed to occur through bicyclic transition states (e.g., 31) in which the silane reagent is covalently bound to the beta-hydroxyl group of the aldehyde and the crotyl group is transferred intramolecularly. This methodology was used to synthesize the C(7)-C(16) segment (58) of zincophorin, which contains a synthetically challenging all-anti stereopentad unit. Surprisingly, 2,3-anti- and 2,3-syn-alpha-methyl-beta-hydroxy aldehydes react in a stereodivergent manner with 24: 2,3-anti-beta-hydroxy aldehydes give the targeted anti,anti-dipropionate adducts with high selectivity, but the reactions of 2,3-syn-beta-hydroxy aldehydes are poorly selective. The stereodivergent behavior of 2,3-syn- vs 2,3-anti-alpha-methyl-beta-hydroxy aldehydes is also exhibited in their reactions with the allyl- (68) and (E)-crotyltrifluorosilanes (27). Competition experiments performed with beta-hydroxy aldehydes 37a (anti) and the corresponding p-methoxybenzyl (PMB) ether 48, and between aldehyde 39 (syn) and the PMB ether 90, established that the 2,3-anti-beta-hydroxy aldehydes react predominantly through bicyclic transition states while the 2,3-syn aldehydes react predominantly through conventional Zimmerman-Traxler transition states. NMR studies established that both the 2,3-syn and the 2,3-anti aldehydes form stable, pentavalent silicate intermediates (98 and 100) with PhSiF(3), but chelated structures 99 and 101 could not be detected. The activation energies for the competing bicyclic and conventional Zimmerman-Traxler transition states were calculated by using semiemperical methods (MNDO/d). These calculations indicate that the stereodivergent behavior of the 2,3-syn-beta-hydroxy aldehydes and the 2,3-anti-beta-hydroxy aldehydes is due to differences in nonbonded interactions in the bicyclic transition states. Specifically, nonbonded interactions in the bicyclic transition states for the allylation/crotylation reactions of the 2,3-syn-beta-hydroxy aldehydes permits the traditional Zimmerman-Traxler transition states to be preferentially utilized.     

Formation of Heterocyclic and Polycyclic Compounds from Amino Alcohols and Dialdehydes

Amino alcohols typically react with aldehydes to produce oxazolidines. It was hypothesized that the condensation of several commercially available amino alcohols with dialdehydes would produce a series of bicyclic oxazolidines containing two secondary amines. However, there were remarkable differences in the type of products formed depending on the structure of the dicarbonyl compounds and the reaction conditions. When linear aliphatic dialdehydes such as glyoxal were used, the expected bis‐oxazolidines were not produced; instead, polycyclic structures or oxazines were formed. However, when cyclic dialdehydes such as 1,3/1,4 cyclohexane dicarboxaldehyde were used, they resulted in products bearing the desired oxazolidine moieties.     

Highly stereoselective three-component reactions of phenylselenomagnesium bromide,acetylenic sulfones,and saturated aldehydes/ketones or alpha,beta-unsaturated enals or enones

beta-Phenylseleno-alpha-tolylsulfonyl-substituted alkenes were synthesized via the three-component conjugate-nucleophilic addition of acetylenic sulfones, phenylselenomagnesium bromide, and carbonyl compounds, such as aldehydes, aliphatic ketones, or alpha,beta-unsaturated enals or enones. The reaction is highly regio- and stereoselective with moderate to good yields. Functionalized allylic alcohols were obtained in the case of aldehydes and aliphatic ketones. In the case of alpha,beta-unsaturated enones, functionalized allylic alcohols or functionalized gamma,delta-unsaturated ketones were obtained, depending on the structures of the ketones.     

Application of organic selenides and tellurides in organic synthesis

This paper describes the progress on the synthesis of organic selenides and tellurides and their application in organic synthesis.Low valent selenium and telluronium compounds having high reducing selectivity can be used to form carbon-hydrogen bonds as special reducing reagents.Telluronium ylides can react with aldehydes and ketones by Wittig-type condensation to produce (E)-configuration alkenes stereoselectively.α-Phenylselanyl arsonium ylides were prepared by transyl-idation reaction of arsonium ylides with phenylselanyl halides which can undergo Wittig-type reactions with carbonyl compounds to give (Z)-α-selanyl-α,β-unsaturated compounds with high stereoselectiv-ity.Zirconium,tin,boron,halogen,metal or hetero-atom were introduced in organoselenium and telluronium compounds as new difunctional group reagents.Under transition metal catalysis,the corresponding cross coupling reactions provide new methods of formation of carbon-carbon double bonds,which were used in the stereoselective synthesis of     

Highly Selective Hydroboration of Alkenes,Ketones and Aldehydes Catalyzed by a Well‐Defined Manganese Complex

Well‐defined manganese complexes based on inexpensive, readily available ligands, 2,2′:6′,2′′‐terpyridine and its derivatives have been prepared and employed for the selective hydroboration of alkenes, ketones and aldehydes. Highly Markovnikov regioselective hydroboration of styrenes as well as excellent chemoselective hydroboration of ketones over alkenes were achieved, for the first time, by an earth‐abundant manganese catalyst.     

Regioselectivity of enamine reactions,preferential 2,2-disubstitution of 2-methylcyclohexanone imines

Secondary enamines derived from imines of unsymmetrical α-substituted ketones react with electrophilic alkenes at the more substituted position to give α,α-disubstituted ketones on hydrolysis.     

Highly Selective Hydroboration of Alkenes,Ketones and Aldehydes Catalyzed by a Well‐Defined Manganese Complex

Well‐defined manganese complexes based on inexpensive, readily available ligands, 2,2′:6′,2′′‐terpyridine and its derivatives have been prepared and employed for the selective hydroboration of alkenes, ketones and aldehydes. Highly Markovnikov regioselective hydroboration of styrenes as well as excellent chemoselective hydroboration of ketones over alkenes were achieved, for the first time, by an earth‐abundant manganese catalyst.     

New Chemistry of Enol Phosphates

Applications of enol phosphates in the synthesis of novel bicyclic 1,3-dienes, bi- and polycyclic aromatic derivatives, and f -hydroxy ketones are described.     

β-Carbonyl radicals as three-carbon building blocks for carbon-carbon bond forming reactions

From aldehydes, ketones and esters β-carbonyl radicals $\text{47}$ can be generated via enolization, cyclopropanation, solvomercuration and reduction with NaBH₄. Radicals $\text{47}$ react with electron-poor alkenes $\text{27}$ to give products of CC-bond forming reactions (Tables 1–3). Carbonyl compounds are therefore precursors of three-carbon building blocks. The products result from reactions with “Umpolung”.     

Stannyl ester cyclizations

Alpha halo stannyl esters react with alkenes to afford lactones. The reaction is catalyzed by AIBN. The reaction proceeds best with electron rich alkenes. The mechanistic aspects of this novel reaction are discussed. This reaction can also be conducted intramolecularly to produce bicyclic lactones. An approach to the lignan system is presented.