Alkylation Michael-type addition

Class (2) reactions are performed in the presence of dilute to concentrated aqueous sodium hydroxide, powdered potassium hydroxide, or, at elevated temperatures, soHd potassium carbonate, depending on the acidity of the substrate. Alkylations are possible in the presence of concentrated NaOH and a PT catalyst for substrates with conventional pX values up to - 23. This includes many C—H acidic compounds such as fiuorene, phenylacetylene, simple ketones, phenylacetonittile. Furthermore, alkylations of N—H, O—H, S—H, and P—H bonds, and ambident anions are weU known. Other basic phase-transfer reactions are hydrolyses, saponifications, isomerizations, H/D exchange, Michael-type additions, aldol, Darzens, and similar... 

Indolo[2,3-d][l,3]thiazine-2,4-dithione formation, 4, 299 Indolothiazines synthesis, 4, 519 Indoloyl azides Curtius rearrangement, 4, 288 Indolyl anions acylation, 4, 232 alkylation, 4, 235 Michael-type additions, 4, 236 Indomethacin... 

With any substrate, when Y is an ion of the type Z—CR2 (Z is as defined above R may be alkyl, aryl, hydrogen, or another Z), the reaction is called the Michael reaction (see 15-21). In this book, we will call all other reactions that follow this mechanism Michael-type additions. Systems of the type C=C—C=C—Z can give 1,2, 1,4, or 1,6 addition. Michael-type reactions are reversible, and compounds of the type YCH2CH2Z can often be decomposed to YH and CH2=CHZ by heating, either with or without alkali. 

Horhold et al. and Lenz et al. [94,95]. The polycondensation provides the cyano-PPVs as insoluble, intractable powders. Holmes et al. [96], and later on Rikken et al. [97], described a new family of soluble, well-characterized 2,5-dialkyl- and 2,5-dialkoxy-substituted poly(pflrfl-phenylene-cyanovinylene)s (74b) synthesized by Knoevenagel condensation-polymerization of the corresponding alkyl-or alkoxy-substituted aromatic monomers. Careful control of the reaction conditions (tetra-n-butyl ammonium hydroxide as base) is required to avoid Michael-type addition. 

Michael-type addition of cyclic amines (piperidine, A-methylpiperazine) to thiazolo[3,2-A][l,2,4]triazole-5(6//)-ones 46 provides an easy entry to 2-aryl(alkyl)-6-(a-aminoarylmethyl)thiazolo[3,2- ][l,2,4]triazol-6(5//)-ones 207 (Equation 19) <1999AF1006, 2001AF470>. 

The base-catalysed addition of thiols to Jt-electron-deficient alkenes is an important aspect of synthetic organic chemistry. Particular use of Triton-B, in place of inorganic bases, has been made in the reaction of both aryl and alkyl thiols with 1-acyloxy-l-cyanoethene, which behaves as a formyl anion equivalent in the reaction [1], Tetra-n-butylammonium and benzyltriethylammonium fluoride also catalyse the Michael-type addition of thiols to a,P-unsaturated carbonyl compounds [2], The reaction is usually conducted under homogeneous conditions in telrahydrofuran, 1,2-dimethoxyethane, acetone, or acetonitrile, to produce the thioethers in almost quantitative yields (Table 4.22). Use has also been made of polymer-supported qua-... 

The importance of chiral thiols and thioether linkages in biological systems has prompted intense investigation of the use of chiral amines [see e.g. 5-11] and ammonium salts [see e.g. 12] as agents for asymmetric induction in the Michael-type addition reaction. Considerable success has been achieved using chinchona alkaloids and their A-alkyl derivatives (see Chapter 12). 

A novel Michael-type addition of alkyl halides to a,/3-enones (239) has been realized using either aquocobalamin (232) or dibromo[l-hydroxy-8H-HDP]cobalt(111)... 

Reduced indole derivatives can be synthesized by using the phenolic oxidation approach. Thus, A-alkyl-A-benzoyltyramines 120, on treatment with IBTA in trifluoroethanol (TFE), followed by aqueous workup, afford the hexahydroindol-6-ones 122. The formation of 122 is rationalized by intramolecular Michael-type addition of amino group to the double bond of the intermediate dienone 121 (91JOC435) (Scheme 33). 

The diquinone 300 has been shown to react with a variety of primary amines producing carbazole quinones 301, a process which presumably involves an intermediate such as 302 formed by Michael-type addition. Alkyl-, aryl-, and heteroarylamines and amino acids have been utilized. The reaction failed with p-nitro- and p-acetylanilines neutral and acidic amino acids required base catalysis. Hydroxyl-... 

Michael-type addition of a suitable nucleophile, e.g. thiols, on to the a,f)-unsaturated lactone. Such alkylation reactions are believed to explain biological activity, and, indeed, activity is typically lost if either the double bond or the carbonyl group is chemically reduced. In some structures, additional electrophilic centres offer further scope for alkylation reactions. In parthenolide (Figure 5.31), an electrophilic epoxide group is also present, allowing transannular cyclization and generation of a... 

Scheme 1.12. A tandem sequence of Michael-type addition and [4 + 2] cycloaddition diastere-oselectively affords highly functionalized 1,2,3,4-derivatives of Cgo (type ( )-169) with two adjacent bridges and a noninherently chiral functionalization pattern. Deprotonation of ( )-169 and subsequent alkylation leads to an inherently chiral addition pattern in ( )-170.

A number of alkylation reactions, Michael-type additions, and base-catalyzed rearrangements have been previously reported for Reissert compounds. These reactions appear to proceed through the conjugate... 

One possible mechanism is the following. The allenyl geminal diester 70 is expected to be susceptible to Michael-type addition of LnPd(O) species to the allenyl sp carbon, resulting in the formation of the palladacyclopropane 71. Insertion of carbon monoxide into 71 and methanolysis afford the triester 72 (Scheme 11-20). The alkene geometry of the product 72 is exclusively E. The high stereoselectivity can be rationalized by assuming that a nucleophilic attack of Pd(0) species on the allenyl sp carbon in 70 takes place from the less-hindered side of a smaller alkyl substituent (R ). Needless to say, in allene 70, the two ester groups are perpendicular to the two substituents Rl and Rg. 

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