Copper-catalyzed beta-Boration of alpha,beta-unsaturated carbonyl compounds: rate acceleration by alcohol additives

[reaction: see text] The efficient addition of bis(pinacolato)diboron to alpha,beta-unsaturated carbonyl compounds with a copper-diphosphine catalyst has been carried out. A dramatic rate acceleration of the reaction was realized by adding alcohol additives. With use of this procedure, a variety of alpha,beta-unsaturated carbonyl compounds including conjugated substrates at the acid oxidation level such as esters and nitriles were reacted to give to the corresponding beta-boryl carbonyl compounds in high yields.     

Iridium-catalyzed transfer hydrogenation of alpha,beta-unsaturated and saturated carbonyl compounds with 2-propanol.

The selective transfer hydrogenation of alpha,beta-unsaturated carbonyl compounds to saturated ones was achieved by the use of 2-propanol as a hydrogen donor under the influence of catalytic amounts of [Ir(cod)Cl](2), 1,3-bis(diphenylphosphino)propane (dppp), and Cs(2)CO(3). Thus, a variety of conjugated enones were allowed to react with 2-propanol in the presence of the [Ir(cod)Cl](2)/dppp/Cs(2)CO(3) system to give the corresponding saturated carbonyl compounds in good to excellent yields without formation of allylic alcohols. Both dppp and Cs(2)CO(3) were essential components to achieve the reduction satisfactorily. Additionally, the reduction of carbonyl compounds to alcohols was also promoted by the same catalytic system. When the reaction of a 1:1 mixture of a conjugated ketone and a saturated ketone with 2-propanol was carried out in the presence of [Ir(cod)Cl](2) combined with dppp and Cs(2)CO(3), the reduction of the alpha,beta-unsaturated ketone was found to take place in preference to that of the saturated ketone.     

Iodine(V) reagents in organic synthesis. Part 4. o-Iodoxybenzoic acid as a chemospecific tool for single electron transfer-based oxidation processes

o-Iodoxybenzoic acid (IBX), a readily available hypervalent iodine(V) reagent, was found to be highly effective in carrying out oxidations adjacent to carbonyl functionalities (to form alpha,beta-unsaturated carbonyl compounds) and at benzylic and related carbon centers (to form conjugated aromatic carbonyl systems). Mechanistic investigations led to the conclusion that these new reactions are initiated by single electron transfer (SET) from the substrate to IBX to form a radical cation which reacts further to give the final products. Fine-tuning of the reaction conditions allowed remarkably selective transformations within multifunctional substrates, elevating the status of this reagent to that of a highly useful and chemoselective oxidant.     

Synthetic scope of Ru(OH)x/Al2O3-catalyzed hydrogen-transfer reactions: an application to reduction of allylic alcohols by a sequential process of isomerization/Meerwein-Ponndorf-Verley-type reduction

Reduction of allylic alcohols can be promoted efficiently by the supported ruthenium catalyst Ru(OH)x/Al2O3. Various allylic alcohols were converted to saturated alcohols in excellent yields by using 2-propanol without any additives. This Ru(OH)x/Al2O3-catalyzed reduction of a dienol proceeds only at the allylic double bond to afford the corresponding enol, and chemoselective isomerization and reduction can be realized under similar conditions. The catalysis is truly heterogeneous and the high catalytic performance can be maintained during at least three recycles of the Ru(OH)x/Al2O3 catalyst. The transformation of allylic alcohols to saturated alcohols consists of three sequential reactions: oxidation of allylic alcohols to alpha,beta-unsaturated carbonyl compounds; reduction of alpha,beta-unsaturated carbonyl compounds to saturated carbonyl compounds; and reduction of saturated carbonyl compounds to saturated alcohols.     

Trends in structure-toxicity relationships for carbonyl-containing alpha,beta-unsaturated compounds

Using toxicity data for 30 aliphatic polarized alpha,beta-unsaturated derivatives of esters, aldehydes, and ketones, a series of six structure-toxicity relationships were evaluated. The structure feature of all assessed compounds, an acetylenic or olefinic moiety conjugated to a carbonyl group, is inherently electrophilic and conveys the capacity to exhibit enhanced toxicity. However, the toxic potency of alpha,beta-unsaturated carbonyl compounds is dependent on the specific molecular structure with several trends being observed. Specific observations include: (1) between homologues, the acetylenic-substituted derivative was more toxic than the corresponding olefinic-substituted one, respectively; (2) between olefinic-homologues, terminal vinyl-substituted derivative was more toxic than the internal vinylene-substituted one; (3) within alpha,beta-unsaturated ketones, methyl substitution on the vinyl carbon atoms reduces toxicity with methyl-substitution on the carbon atom farthest from the carbonyl group exhibiting the greater inhibition; (4) between alpha,beta-unsaturated carbonyl compounds with the carbon-carbon double bond on the end of the molecule (vinyl ketones) and those with carbon-oxygen double bonds on the end of the molecule (aldehydes), the ketones are more toxic than the aldehydes; (5) between homologues of alpha,beta-unsaturated esters, those with additional unsaturated moieties (allyl, propargyl, or vinyl groups) were more toxic than homologues having relevant unsaturated moieties (propyl or ethyl groups); (6) between alpha,beta-unsaturated carbonyl compounds with different shaped alkyl-groups (i.e. different degrees of branching), homologues with straight-chain hydrocarbon moieties were more toxic than those with branched groups.     

Reactions of phenyldimethylsilyllithium with beta-N,N-dimethylaminoenones

Phenyldimethylsilyllithium reacts with the beta-N,N-dimethylaminoenones 1 and 7, with the enal 5, and with ethyl beta-N,N-dimethylaminoacrylate 9 to give the corresponding alpha,beta-unsaturated carbonyl compounds with a beta-phenyldimethylsilyl group, but in the last case only when the reaction mixture is given a mysteriously brief treatment with methyl iodide before workup.     

Asymmetric Lewis acid-catalyzed Diels-Alder reactions of alpha,beta-unsaturated ketones and alpha,beta-unsaturated acid chlorides

[reaction: see text] Conformational analysis, van der Waals attractions, and transition structure calculations are combined to design an asymmetric Lewis acid-catalyzed Diels-Alder reaction for simple acyclic alpha,beta-unsaturated ketones and alpha,beta-unsaturated acid chlorides, giving up to 83 and 92% ee, respectively. The two-point-binding chiral recognition mechanism, Lewis acid-Lewis base coordination with boron and a van der Waals attraction with the naphthyl group, uses the inherent enone unit of simple alpha,beta-unsaturated carbonyl compounds, ending the need for auxiliary oxygen binding sites on the dienophile.     

Diastereoselective addition of organolithiums to 1,3-oxazolidines complexed with aluminum tris(2,6-diphenylphenoxide) (ATPH)

1,3-Oxazolidines were easily obtained by condensation of N-substituted (R)-phenylglycinol with aldehydes. Addition of organolithium reagents to 1,3-oxazolidines by complexation with the bulky Lewis acid aluminum tris(2,6-diphenylphenoxide) (ATPH) readily produced the corresponding chiral amines with good yield and high diastereoselectivity. The configuration of the new stereogenic center was shown to be opposite to that of adducts obtained for the same 1,3-oxazolidines using Grignard reagents. The best diastereoselectivity was achieved using N-isopropyl-1,3-oxazolidines. The mechanism of addition was deduced by determining the stereochemistry of the iminium-aluminum complex by NOE experiments.     

Synthesis of Cp-Re complexes via olefinic C-H activation and successive formation of cyclopentadienes

Treatment of an alpha,beta-unsaturated ketimine with an alpha,beta-unsaturated carbonyl compound in the presence of a rhenium complex, Re2(CO)10, gave a cyclopentadienyl-rhenium complex. This reaction proceeds via rhenium-catalyzed C-H bond activation of an olefinic C-H bond, insertion of an alpha,beta-unsaturated carbonyl compound into a Re-C bond of the alkenylrhenium intermediate, intramolecular nucleophilic cyclization, reductive elimination, elimination of aniline to give a cyclopentadiene derivative, followed by the formation of a cyclopentadienyl-rhenium complex from the cyclopentadiene derivative and the rhenium complex.     

A new method for the synthesis of acyltitanium complexes and their application to copper-mediated acylmetallation of carbon-carbon multiple bonds in aqueous media

Treatment of alpha, beta-unsaturated carbonyl compounds or methyl propargyl ether with acylchlorobis(cyclopentadienyl)titanium in the presence of triethylamine and a copper salt in aqueous THF resulted in acylation of the carbon-carbon multiple bond, yielding the corresponding 1,4-diketones in good yields.     

Synthesis of aromatic (E)- or (Z)-alpha,beta-unsaturated amides with total or very high selectivity from alpha,beta-epoxyamides and samarium diiodide

Highly stereoselective synthesis of aromatic alpha,beta-unsaturated amides was achieved by treatment of aromatic alpha,beta-epoxyamides with samarium diiodide. The starting compounds 1 and 3 are easily prepared by the reaction of enolates derived from alpha-chloroamides with carbonyl compounds at -78 degrees C. A mechanism to explain this transformation is proposed.     

Coordination of Lewis acid to eta(2)-enonepalladium(0) leading to continuous structure variation from eta(2)-olefin type to eta(3)-allyl type.

The reaction of alpha,beta-unsaturated carbonyl compounds, a palladium(0) complex, and Lewis acids led to the formation of a new class of complexes showing a wide variety of structures with eta(2)-type and eta(3)-type coordination of the carbonyl compounds. The reaction of Pd(PhCH=CHCOCH(3))(PPh(3))(2) with BF(3).OEt(2) or B(C(6)F(5))(3) quantitatively gave palladium complexes 1a,b having BX(3)-coordinated eta(2)-enonepalladium structure, as revealed by X-ray structure analysis of the B(C(6)F(5))(3) adduct 1b. On the other hand, the reaction of Pd(PhCH=CHCHO)(PPh(3))(2) with BF(3).OEt(2) or B(C(6)F(5))(3) gave distorted zwitterionic eta(3)-allylpalladium complexes 3a,b, where the Pd-carbonyl carbon distance in 3a (2.413(4) A) is much shorter than that (2.96(1) A) in 1b. The values of the P-P coupling constant and (13)C chemical shift for carbonyl carbon are useful criteria for predicting how the eta(3)-coordination mode contributes to the structure of the enone-palladium-Lewis acid system. Molecular orbital calculations on the series of model complexes suggest that orbital overlap in the highest occupied molecular orbital between the palladium and carbonyl carbon is enlarged by coordination of the Lewis acid to the carbonyl group. Palladium-catalyzed conjugate addition of R-M (R-M = AlMe(3), AlEt(3), ZnEt(2)) and its plausible reaction path are also reported.     

Unprecedented direct oxygen atom transfer from hypervalent oxido-lambda(3)-iodanes to alpha,beta-unsaturated carbonyl compounds: synthesis of alpha,beta-epoxy carbonyl compounds

Tetra-n-butylammonium oxido-lambda(3)-iodane, prepared from 1-hydroxy-1,2-benziodoxol-3(1H)-one by reaction with tetra-n-butylammonium fluoride, directly undergoes oxygen atom transfer to alpha,beta-unsaturated carbonyl compounds, yielding epoxides.     

Tandem cyclization-cycloaddition behavior of rhodium carbenoids with carbonyl compounds: stereoselective studies on the construction of novel epoxy-bridged tetrahydropyranone frameworks

Investigations and stereoselective studies on the tandem reactions of carbonyl ylides generated from alpha-diazo ketones in the presence of carbonyl compounds are presented in this paper. Intramolecular cyclization of rhodium carbenoids generated the transient five- or six-membered-ring carbonyl ylide dipoles, which efficiently underwent 1,3-dipolar cycloaddition reactions with various dipolarophiles such as aromatic aldehydes 15, alpha,beta-unsaturated aldehydes 18/24, alpha,beta-unsaturated ketones 27/28/31, and dienone 34. The transient carbonyl ylides underwent cycloadditions with various aromatic aldehydes to furnish diverse epoxy-bridged tetrahydropyranone ring systems in a diastereoselective manner. The cycloaddition of carbonyl ylides with alpha,beta-unsaturated aldehydes 18/24 or dienone 34 afforded C=O addition products in a chemoselective manner despite the presence of C=C bonds in the above dipolarophiles. Alternatively, the cycloaddition of carbonyl ylides with alpha,beta-unsaturated ketones 27/28 provided both the C=O and C=C cycloaddition products. The cycloaddition of carbonyl ylides with carbonyl compounds occurred in good yields and was found to be highly regio- and stereoselective. Single-crystal X-ray analyses were performed to unambiguously establish the structure and stereochemistry of the novel epoxy-bridged tetrahydropyranone ring systems 35a/38. Compound 35a exhibited both intermolecular C-H...O and intramolecular C-H...pi interaction motifs in the solid-state architecture. The regio-, chemo-, and stereoselectivity observed in these reactions have been investigated by semiempirical AM1 MO calculations. FMO analyses and transition state calculations have been performed for the cycloaddition of carbonyl ylides with alpha,beta-unsaturated carbonyl compounds such as tetracyclone (34) and cyclopentenone (27a). Both FMO and transition state calculations correctly predicted the regio- and stereochemistry of the cycloadducts. The calculations further revealed that a severe steric interaction caused by the phenyl rings present in dipolarophile 34 with dipole 14a increases the activation barrier of the transition state during the cycloaddition process.     

Catalyst-free conjugated addition of thiols to alpha,beta-unsaturated carbonyl compounds in water

[reaction: see text] Catalyst-free conjugate addition of thiols to alpha,beta-unsaturated carbonyl compounds in water is reported. beta-Sulfido carbonyl compounds were formed at room temperature, in short times and with excellent chemoselectivity. Competitive dithiane/dithiolane formation, transesterification, and ester cleavage were not observed. Water played a dual role in simultaneously activating the alpha,beta-unsaturated carbonyl compound and the thiol. This new methodology constitutes an easy, highly efficient, and green synthesis of beta-sulfido carbonyl compounds.     

Palladium/Me(3)SiOTf-catalyzed bis-silylation of alpha,beta-unsaturated carbonyl compounds without involving oxidative addition of disilane

In the presence of a catalytic amount of Me(3)SiOTf and palladium(0), the addition of disilane to alpha,beta-unsaturated carbonyl compounds proceeds under very mild conditions via eta(3)-siloxyallylpalladium generated by the reaction of enone, enal, or aromatic aldehyde with palladium and Me(3)SiOTf.     

Solvent-controlled diastereoselective synthesis of cyclopentane derivatives by a [3 + 2] cyclization reaction of alpha,beta-disubstituted (alkenyl)(methoxy)carbene complexes with methyl ketone lithium enolates

Reaction of alpha,beta-unsaturated methoxycarbene complexes 1 and 11 with methyl ketone lithium enolates 2 leads to the corresponding five-membered carbocyclic compounds 4 or diast-4 and 12. The influence of the solvent and/or cosolvent (PMDTA), which turned out to be crucial to direct the reaction to 4 or diast-4, is studied, and a tentative mechanism according to these facts is proposed. In addition, the reaction of carbene complex 1a with alkynyl methyl ketone lithium enolates can be directed to the formal [3 + 2] or [4 + 1] cyclization products by a slight variation of the reaction conditions. Finally, consecutive three-component coupling reactions with carbene complex 1a, lithium enolates 2, and aldehydes 18 to give, in a diastereoselective way, hydroxy carbonyl compounds 19 and tricyclic polyethers 20 are presented.     

Intramolecular cyclization of tert-butyldiphenylallylsilane units and carbonyl groups: allylsilane terminated cyclization versus the ene reaction.

tert-Butyldiphenylsilylcopper reacts with allene to give an allylsilane-vinylcopper intermediate which upon treatment with alpha,beta-unsaturated ketones leads to allylsilane containing ketones resulting from conjugate addition. These oxoallylsilanes bearing the bulky tert-butyldiphenylsilyl group undergo highly selective intramolecular cyclizations when treated with Lewis acid affording unsaturated cyclopentanols. Two reactivity patterns are observed: allylsilane terminated cyclization involving elimination of silicon or an ene reaction without losing the silyl group. The pathway depends on the ability of a hydrogen beta to the carbonyl to be removed in an ene-type process. Alpha,beta-unsaturated acid chlorides lead to silylated cyclopentenones.     

Highly stereoselective construction of spiro[4.5]decanes by SmI(2)-promoted ketyl radical mediated tandem cyclization

[reaction: see text] Ketyl radical mediated tandem cyclization of omega-alkynyl carbonyl compounds bearing activated alkene using SmI(2) gave spiro[4.5]decanes stereoselectively. In the presence of HMPA, alpha,beta-unsaturated esters and alkenyl phosphonates were converted to spiro[4.5]decanes and a monocyclic compound, respectively. In the presence of Sm, bicyclic lactones were obtained from alpha,beta-unsaturated esters. The spiro[4.5]decane was provided from an alkenyl phosphonate. Interestingly, the stereochemical changeover at the first cyclization has been controlled by means of a variety of activators.     

Chromium-catalyzed pinacol-type cross-coupling: studies on stereoselectivity

A chromium-catalyzed pinacol-type cross-coupling reaction between alpha,beta-unsaturated carbonyl compounds and aldehydes is reported. Even sterically demanding substrates could be coupled to afford the corresponding pinacols in good yields. Systematic studies concerning the origin of the diastereoselectivities led to the proposal of a mechanism for this synthetically useful reaction. Acroleins with alpha-branched alkyl side chains were coupled to give the corresponding syn pinacols, while on the other hand, acroleins with less bulky substituents furnished the anti derivatives. The effects of both the substrates and the reagents on the diastereo- and enantioselectivities were investigated. An unexpected catalytic formation of cyclopropanols was found.