Coupled reactions isomerization

Using a combination of phenyl boronic acid, Pd2(dba)3, tri-ferf-butylphosphine, and potassium fluoride, a tandem Suzuki cross-coupling reaction/isomerization/iminium cyclization sequence was accomplished on A-benzyl-iV-3-bromoprop-2-enyl-1-tryptamine to yield the corresponding l,2,3,4-tetrahydro-/3-carboline in low yield (eq 30). ... 

In the direct coupling reaction (Scheme 30), it is presumed that a coordinatively unsaturated 14-electron palladium(o) complex such as bis(triphenylphosphine)palladium(o) serves as the catalytically active species. An oxidative addition of the organic electrophile, RX, to the palladium catalyst generates a 16-electron palladium(n) complex A, which then participates in a transmetalation with the organotin reagent (see A—>B). After facile trans- cis isomerization (see B— C), a reductive elimination releases the primary organic product D and regenerates the catalytically active palladium ) complex. 

Although analogous to the direct coupling reaction, the catalytic cycle for the carbonylative coupling reaction is distinguished by an insertion of carbon monoxide into the C-Pd bond of complex A (see A—>B, Scheme 31). The transmetalation step-then gives trans complex C which isomerizes to the cis complex D. The ketone product E is revealed after reductive elimination. 

Many other authors studied the catalytic activity of palladium in more complicated hydrogenation reactions because of being coupled with isomerization, hydrogenolysis, and dehydrogenation. In some cases the temperatures at which such reactions were investigated exceeded the critical temperature for coexistence of the (a + /3)-phases in the other case the hydrogen pressure was too low. Thus no hydride formation was possible and consequently no loss of catalytic activity due to this effect was observed. 

The diazotization of amino derivatives of six-membered heteroaromatic ring systems, particularly that of aminopyridines and aminopyridine oxides, was studied in detail by Kalatzis and coworkers. Diazotization of 3-aminopyridine and its derivatives is similar to that of aromatic amines because of the formation of rather stable diazonium ions. 2- and 4-aminopyridines were considered to resist diazotization or to form mainly the corresponding hydroxy compounds. However, Kalatzis (1967 a) showed that true diazotization of these compounds proceeds in a similar way to that of the aromatic amines in 0,5-4.0 m hydrochloric, sulfuric, or perchloric acid, by mixing the solutions with aqueous sodium nitrite at 0 °C. However, the rapidly formed diazonium ion is hydrolyzed very easily within a few minutes (hydroxy-de-diazonia-tion). The diazonium ion must be used immediately after formation, e. g., for a diazo coupling reaction, or must be stabilized as the diazoate by prompt neutralization (after 45 s) to pH 10-11 with sodium hydroxide-borax buffer. All isomeric aminopyridine-1-oxides can be diazotized in the usual way (Kalatzis and Mastrokalos, 1977). The diazotization of 5-aminopyrimidines results in a complex ring opening and conversion into other heterocyclic systems (see Nemeryuk et al., 1985). 

Luchkevich et al. (1986, Table 6) demonstrated that for the three isomeric nitro-benzenediazonium ions and their (Z)-diazohxydroxides the acidity constants can be determined by ultraviolet spectrophotometry, by potentiometry, from the kinetics of reaction with hydroxide ions, from the (Z) (E) isomerization kinetics, and from the kinetics of azo coupling reactions. These independent methods gave surprisingly consistent results. ... 

Besides the azo coupling reactions of 1-methyl- and 2,5-dimethylpyrrole with benzenediazonium-4-sulfonate mentioned above, Butler et al. (1977) synthesized almost all possible combination products of the unsubstituted and four 4-substituted benzenediazonium ions with pyrrole itself, with most isomeric mono-, di-, and trimethyl-pyrroles, and with 3-ethyl-2,4-dimethylpyrrole. These authors also investigated the kinetics of all these combinations (see Sec. 12.7). 

Interesting regioselectivities have been known for more than 100 years for azo coupling reactions with aminonaphthol derivatives such as 6-amino-4-hydroxy-2-naphthalenesulfonic acid (12.136, y-acid), 7-amino-4-hydroxy-2-naphthalenesulf-onic acid (J-acid), and 4-amino-5-hydroxy-2,7-naphthalenedisulfonic acid (H-acid). They give two types of isomeric azo compounds depending on the pH-value of the... 

Auxiliaries (reaction) Substrates By-products Coupled products Isomeric products... 

Denmark pursued intramolecular alkyne hydrosilylation in the context of generating stereodefined vinylsilanes for cross-coupling chemistry (Scheme 21). Cyclic siloxanes from platinum-catalyzed hydrosilylation were used in a coupling reaction, affording good yields with a variety of aryl iodides.84 The three steps are mutually compatible and can be carried out as a one-pot hydro-arylation of propargylic alcohols. The isomeric trans-exo-dig addition was also achieved. Despite the fact that many catalysts for terminal alkyne hydrosilylation react poorly with internal alkynes, the group found that ruthenium(n) chloride arene complexes—which provide complete selectivity for trans-... 

In the Pd-catalyzed cross-coupling reactions of acylzirconocene chlorides with allylic halides and/or acetates (Section 5.4.4.4), the isolation of the expected p,y-unsaturated ketone is hampered by the formation of the a, P-un saturated ketone, which arises from isomerization of the p,y-double bond. This undesirable formation of the unsaturated ketone can be avoided by the use of a Cu(I) catalyst instead of a Pd catalyst [35], Most Cu(I) salts, with the exception of CuBr - SMe2, can be used as efficient catalysts Thus the reactions of acylzirconocene chlorides with allyl compounds (Table 5 8 and Scheme 5 30) or propargyl halides (Table 5.9) in the presence of a catalytic amount (10 mol%) of Cu(I) in DMF or THF are completed within 1 h at 0°C to give ffie acyl--allyl or acyl-allenyl coupled products, respectively, in good yields. ill... 

In addition to benzenoid diazo components, diazotised heterocyclic amines in which the amino group is attached to a nitrogen- or sulphur-containing ring figure prominently in the preparation of disperse dyes [87,88], since these can produce marked bathochromic shifts. The most commonly used of these are the 6-substituted 2-aminobenzothiazoles, prepared by the reaction of a suitable arylamine with bromine and potassium thiocyanate (Scheme 4.31). Intermediates of this type, such as the 6-nitro derivative (4.79), are the source of red dyes, as in Cl Disperse Red 145 (4.80). It has been found that dichloroacetic acid is an effective solvent for the diazotisation of 2-amino-6-nitrobenzothiazole [89]. Subsequent coupling reactions can be carried out in the same solvent system. Monoazo disperse dyes have also been synthesised from other isomeric nitro derivatives of 2-aminobenzothiazole [90]. Various dichloronitro derivatives of this amine can be used to generate reddish blue dyes for polyester [91]. 

An a-allenic sulfonamide undergoes Pd-catalyzed carbonylative cyclization with iodobenzene, affording a mixture of isomeric heterocycles (Scheme 16.12) [17]. The coupling reaction of an allene with a PhCOPdl species takes place at the allenyl central catrbon to form a 2-acyl-Jt-allylpalladium complex, which is attacked by an internal sulfonamide group in an endo mode, affording a mixture of isomeric heterocycles (Scheme 16.13). 

The mechanism of the coupling reaction has been very exhaustively studied. Summarising first what has already been mentioned, it must be noted that the reaction is not confined to the aromatic series, for diazo-compounds condense also with enols and with the very closely related aliphatic aci-nitro-compounds. The final products of these reactions are not azo-compounds, but the isomeric hydrazones formed from them by rearrangement. 

BOP, PyBOP, HBTU, HATU, and so forth with an additive It has been considered essential to use an additive with these reagents because the tertiary amine required to effect the coupling promotes isomerization. Diisopropylethylamine or possibly trimethylpyridine are the bases of choice to minimize the side reaction, but the additive may increase isomerization (see Section 7.18). 

Ir-diphosphine complexes have been shown to catalyze a number of potentially interesting C—C coupling reactions [41]. Special mention should be made of the various transformations of alkynes (cycloaddition, isomerization, dimerization, alkynylation), selected aldol and carbonylation reactions, even though the synthetic potential of some of these reactions has not been explored. 

Picryl chloride has been used successfully in a number of copper-mediated Ullmann coupling reactions. 2,2, 4,4, 6,6 -Hexanitrobiphenyl has been synthesized by heating picryl chloride with copper powder. The same reaction in the presence of a hydride source (hot aqueous alcohol) yields 1,3,5-trinitrobenzene (TNB). The Ullmann reactions between picryl chloride and isomeric iodonitrobenzenes with copper bronze in DMF has been used to synthesize 2,2, 4,6-, 2,3, 4,6-, and 2,4,4, 6-tetranitrobiphenyls. ... 

Saturated 5(4//)-oxazolones are easily obtained from //-acylamino acids in the presence of a cyclization agent and have been used extensively in coupling reactions as synthetic equivalents of a-amino acids in the synthesis of peptides. In this context, tautomeric equilibrium can be a significant problem due to the racemization associated with the isomerization. For example, trifluoroacetylation of tryptophan in ether affords the 5(4//)-oxazolone 5 without racemization. However, upon dissolution in acetonitrile, 5 completely racemizes. Further, upon heating, an aqueous dioxane solution of 5 cleanly isomerizes to the isomeric 5(2//)-oxazolone 6 (Scheme 7.2). 

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