Aldol reaction tandem reactions

Krische reported an intramolecular version of the tandem conjugate addition-aldol reaction. The reaction of enone-ketone 58 with phenylboronic acid 2 m occurs in diox-... 

Michael-aldol reaction tandem. The copper hydride reagent reduces the double bond... 

Tandem conjugate addition ofenolates and aldol reactions Tandem conjugate addition of chiral amines and aldol reactions Part III - Intermediate is an Unstable Imine or Enamine Intermediate Would Be Formed by Amide Condensation... 

The triethylsilyl ether of a,a-diphenylprolinol 2B induces the Michael-aldol reaction tandem that combines A -protected o-aminobenzaldehydes and 2-alkenals to form chiral 2-substituted 3 -formyl-1,2-dihydroquinolines. ... 

Michael-aldol reaction tandem. Addition of lithium benzenethiolate to conjugated esters in the presence of aldehydes is followed by an aldol reaction in a stereoselective manner. 

Michael and aldol reaction tandem. Michael reaction products arising from dicarbonyl compounds that contain one conjugated double bond undergo cyclization (aldol reaction) if the second carbonyl group is properly juxtaposed. For example, a synthesis of 2-hydroxycyclohexanecarboxylic acid derivatives is accomplishable in one step from 7-keto-2-alkenamides. The tandem reaction is promoted by MejAlCl. 

Michael-aldol reaction tandem. Fischer carbene Mo complexes containing a difluoroboroxy group, that is R—C(OBF2)=Mo(CO)5, donate R to enones. The adducts may be trapped with aldehydes. ... 

Lewis Acid Catalyzed Reactions. S amarium iodide catalyzes several transformations by presumably acting as a Lewis acid. For example, it is an efficient catalyst for the imino-Diels-Alder (eq 70) and for imino-aldol reactions. Tandem Mukaiyama-Michael-aldol (eq 71) and Michael imino-aldol processes have also been reported. ... 

Shibasaki has also extended the use of LLB catalyst to tandem nitro-aldol reactions providing bicyclic adducts with 65% ee (Eq. 3.75).124... 

Combining, in tandem, the nitro-aldol reaction with the Michael addition using thiophenol is a good method for the preparation of P-nitro sulfides as shown in Eqs. 4.2 and 4.3. This reaction is applied to a total synthesis of tuberine. Tuberine is a simple enamide isolated from Streptomyces amakusaensis and has some structural resemblance to erbastatin, an enamide which has received much attention in recent years as an inhibitor of tyrosine-specific kinases. The reaction of p-anisaldehyde and nitromethane in the presence of thiophenol yields the requisite P-nitro sulfide, which is converted into tuberine via reduction, formylation, oxidation, and thermal elimination of... 

Figure 14.12 Asymmetric tandem aldol reaction using 2-deoxyribose-5-phosphate aldolase (DERA) and its application for production of Atorvastatin...

Allylic alcohols react with aldehydes, in the presence of catalytic amounts of Fe(CO)s under photochemical activation conditions, to give mainly aldol products (Scheme 11).33 This novel tandem iosmerization-aldolization reaction is a process with a perfect atom economy, proceeding under neutral conditions. 

Tandem aldol reaction/siloxy-Cope rearrangement equivalent 181... 

A similar method has been described by Badia and co-workers who used chiral amides derived from pseudoephe-drine.139 Moreover, a zirconium-mediated Claisen-aldol tandem reaction of an a,cr-dialkylated ester with several aldehydes has been reported (Scheme 39).140 After the initial Claisen condensation, zirconium enolate intermediate 92 reacts with various types of aldehydes through aldol-type reaction and subsequent lactonization, providing the corresponding pyran-2,4-diones. 

Silyltitanation of 1,3-dienes with Cp2Ti(SiMe2Ph) selectively affords 4-silylated r 3-allyl-titanocenes, which can further react with carbonyl compounds, C02, or a proton source [26]. Hydrotitanation of acyclic and cyclic 1,3-dienes functionalized at C-2 with a silyloxy group has been achieved [27]. The complexes formed undergo highly stereoselective addition with aldehydes to produce, after basic work-up, anti diastereomeric (3-hydroxy enol silanes. These compounds have proved to be versatile building blocks for stereocontrolled polypropionate synthesis. Thus, the combination of allyltitanation and Mukayiama aldol or tandem aldol-Tishchenko reactions provides a short access to five- or six-carbon polypropionate stereosequences (Scheme 13.15) [28],... 

T. Arai, H. Sasai, K. Aoe, K. Okamura, T. Date, M. Shibasaki, A New Multifunctional Heterobimetallic Asymmetric Catalyst for Michael Additions and Tandem Michael-Aldol Reactions, Angew. Chem. Int. Ed Engl 1996, 35,104-106. 

Several attempts to take advantage of the intermediate boron enolate to achieve tandem conjugate addition-aldol reaction have been proposed [71]. Recently, Chandrasekhar [72] reported the addition of triethylborane to methyl vinyl ketone followed by the in situ trapping of the enolate by aromatic aldehyde (Scheme 26). 

Scheme 26 Tandem conjugate addition-aldol reaction...

Tandem processes mediated by triethylborane involving conjugate addition to enones followed by aldol reaction are reported (Scheme 52, Eq. 52a). More recently, a tandem process involving addition of an isopropyl radical to an o ,/3-unsaturated oxime ether afforded an azaenolate intermediate that reacts with benzaldehyde in the presence of trimethylaluminum. The aldol product cyclizes to afford an isopropyl substituted y-bulyroloaclonc in 61% overall yield (Scheme 52) [116]. In these reactions, triethylborane is acting as a chain transfer reagent that delivers a boron enolate or azaenolate necessary for the aldolization process. 

The aldol reaction is probably one of the most important reactions in organic synthesis. In many industrially important hydroformylation processes selfcondensation of aldehydes is observed. Sometimes this consecutive reaction is favored as in the production of 2-ethyl hexanol. But synthetic applications of tandem hydroformylation/aldol reactions seem to be limited due regiose-lectivity problems of a mixed aldol reaction (Scheme 28). However, various tandem hydroformylation/intramolecular mixed aldol reactions have been described. 

Although the saturated ketone can be obtained in nearly quantitative yields, the loss of synthetically valuable functionality is unfavorable and can be overcome by a modification of the tandem sequence. The use of the corresponding unsaturated silyl enol ethers in a tandem hydroformyla-tion/Mukaiyama aldol reaction gives the desired aldol adduct with complete... 

This method can also be applied to silyl enol ethers of homologous unsaturated ketones as well as of unsaturated aldehydes or esters [85-87]. While unmodified unsaturated esters give only the corresponding aldehydes without cyclization under tandem hydroformylation/aldol reaction conditions, the corresponding silylated ester enolates smoothly cyclize in a tandem hy-droformylation/ Mukaiyama aldol reaction (Scheme 32) [85-87]. 

Very recently, a tandem sequence consisting of enolboration/hydroform-ylation/aldol reaction has been described [88]. Here configuration of the enol boronate is transferred to the aldol product, allowing good to excellent di-astereoselectivities in the hydroformylation/aldol reaction. With this method, 5-7-membered rings are obtained in excellent yields (Scheme 35). 

Zirconium tetrachloride promotes a tandem nucleophilic addition and aldol-type condensation reaction of methyl propynoate, or /V,/V-dimethylpropynamidc, with aldehydes, or ketones, in the presence of tetra-n-butylammonium iodide (Scheme 6.13) [8] with a high selectivity towards the formation of Z-isomers. A similar reaction occurs between aliphatic and aromatic aldehydes and penta-3,4-dien-2-one to yield 1-substituted 2-acetyl-3-iodobut-3-enols (50-75%) [9]. 

Tandem addition-aldol reaction with methyl propiolate... 

Scheme 7.14. Enantioselective tandem conjugate addition-aldol reactions.

Very recently, a catalytic enantioselective route to prostaglandin i methyl ester was developed based on a tandem 1,4-addition-aldol reaction [84]. 

Q -Phenylthiomethyl-jS-hydroxy esters (50) can be prepared, predominantly as the iyn-isomer, by a stereoselective one-pot Michael-aldol tandem reaction. The seleno analogue can similarly be prepared (again, mainly syn), using PhSeLi in diethyl ether, but phenoxide ion is not sufficiently reactive for this sequence. 

Novel aldol-type reactions under Cinchona-deriwed chiral thiourea catalysis was reported by Wang et al. [78]. In their report, a novel cascade Michael-aldol reaction was presented. The reaction involves a tandem reaction catalyzed via hydrogen-bonding with as little as 1 mol% catalyst loading to generate a product with three stereogenic centers (Scheme 28). hi the reaction of 2-mercaptobenzaldehyde 128 and a,P-unsatnrated oxazolidinone 129, the desired benzothiopyran 130 was formed smoothly in high yield and excellent stereoselectivity. 

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