A new synthesis of β,γ-unsaturated esters from three components, aldehydes, chloromethyl p-tolyl sulfoxide, and tert-butyl acetate, via magnesium carbenoid 1,2-CH and 1,2-CC insertion as the key reaction

Addition reaction of 1-chlorovinyl p-tolyl sulfoxides, which were derived from various aldehydes, with lithium enolate of tert-butyl acetate at −78 °C in THF gave adducts in high yields. Magnesium carbenoids were generated by treatment of these adducts with Grignard reagents via the sulfoxide-magnesium exchange reaction. When the adducts were derived from alkyl aldehydes or electron-deficient aromatic aldehydes, carbenoid 1,2-CH insertion reaction took place from the magnesium carbenoids to afford β,γ-unsaturated butyric esters having a substituent at the β-position. On the contrary, when the adducts were derived from electron-rich aromatic aldehydes, carbenoid 1,2-CC insertion reaction took place from the magnesium carbenoids to give β,γ-unsaturated butyric esters having the aromatic group at the γ-position. Highly stereospecific 1,2-CC insertion reactions were observed in the latter reactions. This procedure provides a good way for a synthesis of β,γ-unsaturated esters from aldehydes with two carbon-carbon bond-formations.     

A synthesis of di- and tri-substituted β,γ-unsaturated esters from aldehydes by the magnesium carbenoid 1,2-CH and 1,2-CC insertion as the key reaction

Addition reaction of 1-chlorovinyl p-tolyl sulfoxides, which were derived from aldehydes, with lithium enolate of tert-butyl acetate at −78 °C in THF gave adducts in high yields. Treatment of these adducts with Grignard reagents resulted in the formation of magnesium carbenoids via the sulfoxide-magnesium exchange reaction. When the adducts were derived from alkyl aldehydes or electron-deficient aromatic aldehydes, carbenoid 1,2-CH insertion reaction took place from the magnesium carbenoids to afford β,γ-unsaturated butyric esters having a substituent at the β-position. On the other hand, when the adducts were derived from electron-rich aromatic aldehydes, carbenoid 1,2-CC insertion reaction took place from the magnesium carbenoids to give β,γ-unsaturated butyric esters having the aromatic group at the γ-position. Highly stereospecific 1,2-CC insertion reactions were observed in the latter reactions. When the addition reactions were quenched with iodoalkanes, the alkylated adducts were obtained in quantitative yields. Tri-substituted β,γ-unsaturated esters, or in some case γ,δ-unsaturated esters, were obtained by the treatment of the alkylated adducts with EtMgCl. These procedures provide a good way for a new synthesis of di- and tri-substituted β,γ-unsaturated esters from aldehydes with two or three carbon-carbon bond-formations.     

Bifunctional chiral phosphine-containing Lewis base catalyzed asymmetric Morita–Baylis–Hillman reaction of aldehydes with activated alkenes

A series of novel bifunctional chiral phosphine-containing Lewis bases were synthesized and successfully applied to the asymmetric Morita–Baylis–Hillman reaction of aldehydes with methyl vinyl ketone (MVK) and ethyl vinyl ketone (EVK) to give the corresponding adducts in moderate yields and enantioselectivities under mild reaction conditions.     

Synthesis of conjugated enynes from ketones and aldehydes by 1,2-CC insertion and 1,2-CH insertion of carbenoids as the key reactions

The addition reactions of 1-chlorovinyl p-tolyl sulfoxides, which were derived from ketones and chloromethyl p-tolyl sulfoxide, with lithium acetylides gave adducts in moderate to good yields. Treatment of the adducts with Grignard reagents resulted in the formation of conjugated enynes in good to high yields via the 1,2-carbon-carbon insertion (1,2-CC insertion) reaction of the generated magnesium carbenoid intermediates. On the other hand, the addition reactions of 1-chlorovinyl p-tolyl sulfoxides derived from aldehydes with lithium acetylides directly gave conjugated enynes bearing a p-tolyl sulfinyl group at the 1-position through the 1,2-carbon-hydrogen insertion (1,2-CH insertion) reaction of the generated lithium carbenoid intermediates. These procedures provide a good way for the synthesis of multi-substituted conjugated enynes from ketones and aldehydes.     

The Chemistry of Coumarin Derivatives. Part 5. Unusual course of the reaction of 4-hydroxycoumarin and aliphatic aldehydes

The reaction of 4-hydroxycoumarin and certain aliphatic aldehydes affords 1:1 or complex 2:2 adducts besides (or in place) of the expected 2:1 bis(coumarin) adducts. Reaction with heptanal, cyclohexanecarbaldehyde, and pivalaldehyde are reported as representative. The structure of the reaction products was established by spectroscopical techniques, including X-ray analysis, and their formation was mechanistically rationalized. Some of the 1:1 adducts are synthetically useful for the preparation of 3-alkyl-4-hydroxycoumarins.     

1-Methylimidazole 3-N-oxide as a new promoter for the Morita-Baylis-Hillman reaction

The Morita-Baylis-Hillman reaction of aldehydes with α,β-unsaturated ketones can be affected by the Lewis bases. We have found that 1-methylimidazole 3-N-oxide promoted the Morita-Baylis-Hillman reaction of various activated aldehyde compounds in non-solvent system. This is a mild reaction condition and requires no special equipment to give the Morita-Baylis-Hillman adducts.     

Aluminum enolates via retroaldol reaction: catalytic tandem aldol-transfer—Tischtschenko reaction of aldehydes with aldol adducts of ketones to ketones

Bidentate aluminum chelates derived from biphenol, binaphthol and catechol were found to be efficient catalysts for aldol-transfer reactions of ketone to ketone aldol adducts with aliphatic or aromatic aldehydes giving rise to the formation of aldol adducts of ketones to the aldehydes. In the presence of an excess of an aliphatic aldehyde, a catalytic tandem aldol-transfer—Tischtschenko reaction is observed. The tandem reaction produces monoesters of 1,3-diols with high anti selectivity and with modest to good chemical yield. 1,2-Unsaturated aldehydes are less reactive in the aldol-transfer reaction and require 2-4 times higher load of the catalyst to be used than aliphatic and aromatic aldehydes. Poor diastereoselectivity was observed in the formation of α-substituted aldols and 2-substituted monoesters of anti-1,3-diols indicating that the aldol-transfer reaction is not diastereoselective with the catalysts studied. The utility of the highly 1,3-anti selective formation of diolmonoesters was found to be limited by acyl migration.     

Addition reactions and redox esterifications of carbonyl compounds by N-heterocyclic carbenes of indazole

Thermal decarboxylation converts 1,2-dimethylindazolium-3-carboxylate into indazol-3-ylidene, which reacts in situ with ketones to form stable 1:1 adducts. When the reaction is conducted with aromatic aldehydes in alcohols, redox esterifications to benzoates are observed. Model reactions such as redox esterifications of aromatic aldehydes with sodium alcoholates in the presence of 1,2-dimethylindazolium salt and oxidations of sodium benzylates by 1,2-dimethylindazolium salt to aldehydes lend support to a Cannizzaro-type mechanism of this reaction.     

Enantioselective organocatalytic aldehyde-aldehyde cross-aldol couplings. The broad utility of α-thioacetal aldehydes

An asymmetric proline catalyzed aldol reaction with α-thioacetal aldehydes has been developed. Thioacetal bearing aldehydes readily participate as electrophilic cross-aldol partners with a broad range of aldehyde and ketone donors. High levels of reaction efficiency as well as diastereo- and enantiocontrol are observed in the production of anti-aldol adducts.     

A convenient stereoselective synthesis of β-lactams from β-hydroxy-α-thioalkylesters prepared from Michael/aldol tandem reaction or stereoselective addition of thiols to the Baylis-Hillman adducts

A convenient stereoselective synthesis of β-lactams from thio-Michael/aldol tandem adduct is described. syn-Selective tandem reaction followed by amidation and intramolecular S_N2 reaction provided β-lactams in diastereomerically pure form. The tandem reaction with aliphatic aldehydes, on the other hand, afforded a mixture of diastereomers of corresponding tandem adducts in about 3:1 ratio so that the conversion to β-lactams afforded a diastereomeric mixture. As an alternative approach to prepare the tandem adducts, the stereoselective Michael addition of aliphatic thiols to Baylis-Hillman adduct was developed. The stereoselectivity was sensitive to the protective group at the hydroxyl group and TBS protection brought the most successful syn-selective formation of the tandem adducts. The procedure could be applied to the ketone derivatives of the Baylis-Hillman adduct but no selectivity was observed for the nitrile-Baylis-Hillman adducts. A similar conversion of the adduct provided desired β-lactams stereoselectively.     

Diastereoselective additions of chiral vinylzinc reagents to alpha-chiral aldehydes

[reaction: see text] Additions of vinylic zinc bromide reagents to alpha-chiral aldehydes (R(1) = CH(2)OTBS, R(2) = Me; R(1) = Me, R(2) = OTBS) in the presence of lithiated (+)- or (-)-N-methylephedrine proceed with predominant reagent control to afford anti or syn adducts stereoselectively, except when the aldehydes possess an alkoxy substituent at the alpha- or beta-positions (R(1) = Me, R(2) = OBn; R(1) = CH(2)OBn, R(2) = Me), in which case chelation-controlled adducts predominate.     

Initiator-dependent chemoselective addition of THF radical to aldehyde and aldimine and its application to a three-component reaction

[reaction: see text] The product distribution of the three-component reaction of aldehydes, arylamines, and THF was dependent on a radical initiator, preferentially giving the corresponding THF adducts of imines with dimethylzinc and adducts of aldehyde with triethylborane.     

Stereochemical aspects of formation of substituted hydrogenated 3-(1-pyridinio)-6-pyridinethiolates and synthesis of 4,6-diaryl-3-cyano-2(1H)-pyridinethiones on their basis

Regioselective and stereoselective methods were developed for the synthesis of 2-hydroxy-2,4-diaryl-3-(1-pyridinio)-5-cyano-3,4-trans-1,2,3,4-tetrahydropyridine-6-thiolates on the basis of the reactions of cyanothioacetamide with E-1-styrylpyridinium salts or aromatic aldehydes and 1-phenacyl-pyridinium bromide. The products exist in the half-chair conformation with the trans-diaxial arrangement of hydrogen atoms 3 and 4. The Michael adducts in the form of the anti conformers with the synclinal arrangement of the reaction centers act as intermediates. The obtained thiolates were converted with high yields into 4,6-diaryl-3-cyano-2(1H)-pyridinethiones.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 370–375, March, 1990.     

Chiral phosphine oxide BINAPO as a Lewis base catalyst for asymmetric allylation and aldol reaction of trichlorosilyl compounds

Chiral phosphine oxide BINAPO, which was readily prepared from chiral phosphine BINAP, exhibited good catalytic activities in the reaction of trichlorosilyl compounds via hypervalent silicate intermediates. The allylation of aldehydes with allyltrichlorosilanes in the presence of a catalytic amount of BINAPO gave the allylated adducts in good enantioselectivities (up to 79% ee) wherein a combination of diisopropylethylamine and tetrabutylammonium iodide as additives was crucial to accelerate the catalytic cycle. ³¹P NMR analysis of the phosphine oxide suggested that the amine promoted the dissociation of phosphine oxide from silicon atom. BINAPO also promoted the enantioselective aldol reaction of aldehydes with trichlorosilyl enol ethers in the presence of diisopropylethylamine as an additive to afford the corresponding aldol adducts in high diastereo- and enantioselectivities (up to syn/anti=1/25, 96% ee (anti)).     

Aroxydihydropyrans

The reaction of vinyl ethers and vinyl Sulfides of the quinoline series with unsaturated aldehydes gives 3,4-dihydro-2-pyranyloxy(mercapto)quinolines, in the hydrogenation of which, depending on the conditions, the multiple bonds in the pyran or pyridine ring are reduced. The ionization constants of the adducts were established by potentiometry. The vinyl ethers of 6-hydroxyquinoline, 8-hydroxy-1,2,3,4-tetrahydroquinoline, and 8-(S-vinyl)mercaptoquinoline were obtained for the first time.See [1] for communication X.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 375–378, March, 1976.     

Synthesis Of 2-Acyltetrahydro-β-Carbolines By An Intramolecular α-Amidoalkylation Reaction

2-Acyltetrahydro-β-carbolines 7 have been obtained by cyclization of adducts 5 from imines 3 of tryptamine 1 and aldehydes 2 with acyl chlorides 4 as a result of an intramolecular a-amidoalkylation reaction in the presence of bases as N,N-dimethylaniline or Et₃N.     

Synthesis of Morita-Baylis-Hillman-type adducts by unprecedented reaction of 1-phenyl-2-(trimethylsilyl)acetylene with aromatic aldehydes catalyzed by quaternary ammonium fluorides derived from cinchonine

The quaternary ammonium fluoride derived from cinchonine efficiently catalyzed the reaction of 1-phenyl-2-(trimethylsilyl)acetylene with aromatic aldehydes to give the β-branched Morita-Baylis-Hillman-type adducts.     

Synthesis of vinyl ethers by homologation of aldehydes via radical reductive elimination

Methoxyphenylthiomethyllithium 1 reacts with aldehydes to give adducts which are then transformed into xanthates. These compounds, by reaction with tri-n-butylstannane, afford vinyl ethers in good yields.     

Catalytic Enantioselective Quick Route to Aldol‐Tethered 1,6‐ and 1,7‐Enynes from ω‐Unsaturated Aldehydes

An effective asymmetric route to functionalized 1,6‐ and 1,7‐enynes has been developed based on a direct cross‐aldol reaction between ω‐unsaturated aldehydes and propargylic aldehydes (α,β‐ynals) promoted by combined α,α‐dialkylprolinol ether/Brønsted acid catalysis. This synergistic activation strategy is key to accessing the corresponding aldol adducts with high stereoselectivity, both enantio‐ and diastereoselectivity. The aldol reaction also proceeds well with propargylic ketones (α,β‐ynones) thus enabling a stereocontrolled access to the corresponding tertiary alcohols. The utility of these adducts, which are difficult to prepare through standard methodology, is demonstrated by their transformation into trisubstituted bicyclic enones using standard Pauson–Khand conditions.     

New synthesis of multisubstituted cyanocyclopropanes by the intramolecular SN2 alkylation and 1,3-CC insertion reaction of magnesium carbenoids as the key reactions

Addition reaction of 1-chlorovinyl p-tolyl sulfoxides derived from ketones and aldehydes with lithium α-cyano carbanions gave nitrile adducts in high to quantitative yields. Treatment of the nitrile adducts derived from acetonitrile with excess i-PrMgCl in THF resulted in the formation of cyanocyclopropanes via the intramolecular S_N2 alkylation of the generated magnesium carbenoids. The intermediate of this reaction was proved to be a cyclopropylmagnesium chloride and was reactive with electrophiles to give multisubstituted cyanocyclopropanes. On the other hand, the reaction of the nitrile adducts derived from arylacetonitriles with i-PrMgCl resulted in the formation of 2-arylcyanocyclopropanes by the 1,3-carbon–carbon (1,3-CC) insertion reaction of the generated magnesium carbenoid intermediates. This reaction was found to proceed in a highly stereospecific manner. The key reactions, intramolecular S_N2 alkylation and 1,3-CC insertion reaction of the magnesium carbenoids, are the first examples for the reaction of the magnesium carbenoids bearing a nitrile functional group.