Acyl derivatives cross-coupling

The lithiation of an O-vinyl carbamate with rAr-BuLi followed by transmetallation with zinc bromide provides the convenient acyl anion derivative, which undergoes smooth Pd(0)-catalyzed cross-coupling reactions (Equation (24)).67 This reaction sequence has been extended to lithium enolates. The deprotonation of the aminoester with LDA followed by a transmetallation with zinc bromide in ether furnishes a zinc enolate, which readily adds to the double... 

N-Arylated 1,3-propanesultams 236 (R =Ar, R = H) are efficiently prepared from a Pd-catalyzed cross-coupling reaction with different aryl bromides in the presence of Xantphos <2004TL3305>. N-Fluorinated (-l-)-camphorsultams 237 (X = H, Cl, OMe R = F) have been prepared the corresponding imine 16 and difluoro derivative 238 were formed as by-products. The use of 237 is reported in Section 4.05.12.1 <1998JOC9604>. The syntheses of Ar-(l-alkynyl)-Oppolzer s sultams are reported in Section 4.05.6.3.4. Many examples of acylated Oppolzer s sultams are reported in Section 4.05.12.1. 

Further detailed information on the reactive excited states of p. -unsaturated ketones has been acquired with (3a-c). Inefficient intersystem crossing from the singlet to the triplet state precedes population of Tz(.n,Tt ) from which the 1,3-acyl shift, induced by Norrish type I cleavage, occurs more readily than internal conversion to Ti Ti has been estimated to lie within 8 W mol of the acetone triplet (335 kJ mol ). That the 1,3-acyl shift is coupled not only with singlet-state but also Tz-state reactivity has been unequivocally shown by two methods. Thermal decomposition of a dioxetane, a derivative of (3a), generates predominantly the T2 state from which the 1,3-acyl shift product is formed concurrently with the ODPM products (4a) and (5a) via A photo-CIDNP study has independently demon-... 

The thiazolium-catalyzed addition of an aldehyde-derived acyl anion with a Michael acceptor (Stetter reaction) is a well-known synthetic tool leading to the synthesis of highly funtionalized products. Recent developments in this area include the thiazolylalanine-derived catalyst 191 for asymmetric intramolecular Stetter reaction of a,P-unsaturated esters <05CC195>. However, these cyclizations proceed only in moderate enantioselectivities and yields even under optimized conditions. Thiazolium salt 191 has been used successfully for enantioselective intermolecular aldehyde-imine cross coupling reactions <05JA1654>. Treatment of tosylamides 194 with aryl aldehydes in the presence of 15 mol% of 191 and 2... 

Enol phosphates derived from iV-acyl-piperidin-2-one (or 2-oxoazepane) can be utilized in cross-coupling... 

Reductive cross-coupling of carbonyl compounds. The low-valent titanium species couples ketones to nitriles and carboxylic acid derivatives such as esters and acid chlorides. The products represent reductive acylation products of ketones. ... 

Several N-protected indol-2-yltributylstannanes were examined in Pd-catalyzed cross-coupling with aryl halides and triflates, acyl chlorides and benzylic and allylic bromides. <94J0C4250> The 1-methyl and l-(2-trimethylsilylethoxymethyl) (SEM) derivatives reacted readily whereas the 1-t-butoxycarbonyl derivative was somewhat less reactive. The SEM group is removable with BU4N F , providing acces to the deprotected 2-substituted indoles. 

Consequently, pyridine has a reduced susceptibility to electrophilic substitution compared to benzene, while being more susceptible to nucleophilic attack. One unique aspect of pyridine is the protonation, alkylation, and acylation of its nitrogen atom. The resultant salts are still aromatic, however, and they are much more polarized. Details for reactivity of pyridine derivatives, in particular, reactions on the pyridine nitrogen and the Zincke reaction, as well as C-metallated pyridines, halogen pyridines, and their uses in the transition metal-catalyzed C-C and C-N cross-coupling reactions in drug synthesis, will be discussed in Section 10.2. 

Various Pd-catalyzed carbonylation reactions have often been referred to as carbonyla-tive cross-coupling reactions (Scheme 4). However, these reactions involving the formation of two C—C bonds with incorporation of CO clearly display a pattern of chemical transformation that is different from Scheme 1. So, these reactions are discussed in Parts VI and VIII. On the other hand, Pd-catalyzed acylation with acyl halides and related derivatives are examples of the reaction represented by Scheme 1, where is acyl, and they are therefore discussed in this Part (Sect. III.2.12.1), even if CO may be used to prevent decarbonylation. 

First, coordinatively unsaturated active palladium catalyst, PdL2, is produced via dissociation of the ligands, which then reacts with acyl halide to give the acylpalladium intermediate. Since deinsertion of CO of the acylpalladium derivatives may occur simul-taneously, the next step, transmetallation (so-called metathesis), is the most crucial for the efficiency of the overall reaction. A variety of organometallic compounds, such as boron, aluminum, copper, zinc, mercury, silicon, tin, lead, zirconium, and bismuth, are used as the partner in this coupling reaction without loss of CO. In this section, the important features of the cross-coupling reactions of a variety of organometallic compounds with acyl halides and related electrophiles are discussed. 

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