Amines alkynyl

Cyclization of Alkynyl Amines, Alkynyl Ethers, Alkynyl Sulfides, and Alkynyl Selenides... 

In addition to alcohols, some other nucleophiles such as amines and carbon nucleophiles can be used to trap the acylpalladium intermediates. The o-viny-lidene-/j-lactam 30 is prepared by the carbonylation of the 4-benzylamino-2-alkynyl methyl carbonate derivative 29[16]. The reaction proceeds using TMPP, a cyclic phosphite, as a ligand. When the amino group is protected as the p-toluenesulfonamide, the reaction proceeds in the presence of potassium carbonate, and the f>-alkynyl-/J-lactam 31 is obtained by the isomerization of the allenyl (vinylidene) group to the less strained alkyne. 

McDowell and Stirling194 studied electronic effects upon the reactivity of aryl vinyl sulfones towards amines. Rate constants for t-butylamine addition in ethanol at 25 °C were well correlated by the Hammett equation, with p = 1.59. Comparison of this with p values for H-D exchange mentioned above191 suggested considerable carbanionic character in the transition state, perhaps in a concerted mechanism. Rates of addition of amines to alkenyl, allenyl and alkynyl p-tolyl sulfones have also been measured195. 

An alternative preparation of benzofurans was carried out via a microwave-assisted Mannich condensation of paraformaldehyde and a secondary amine followed by cyclization with an alkynyl phenol 185 mediated by alumina doped with Cul (Scheme 67). The reaction can be carried out in a single-step... 

C. Reactions not involving P=0 or P=S Groups.—Enamine phosphine oxides (45) have been prepared by the addition of amines to 1-alkynyl-phosphine oxides, and the reactions of their anions with various electrophiles have been reported. - With ketones a Wittig-type reaction leads to the formation of a/3-unsaturated ketones, in 53—70% yield, while with epoxides cyclopropyl ketimines are formed. A Diels-Alder reaction of l-phenyl-A -phospholen-l-oxide (46) with 1,4-diacetoxybutadiene has been used in the preparation of l-phenyl-benzo[/>]phosphole (47), as... 

Subshtuted 3-alken-l-ynes can be hydroaminated with primary or secondary aliphahc or aromatic amines at the alkynyl sites or at the alkynyl and at the alkenyl sites in the presence of Hg(ll) salts. However, the reachon is essentially stoichiometric in nature, even if the mercury compound can be recycled without apparent loss of achvity [262-264]. 

McLaughlin and co-workers have described a one-pot copper-free Sonogashira alkynylation and base-mediated indolization reaction to access 1,2-disubstituted indoles 125 and azaindoles from o-chloroanilines 123 <060L3307>. A ligand-, copper, and amine-free variant of the Sonogashira coupling was used by Srinivasan and co-workers to access 2-substituded indoles <06T5109>. 

The amine adduct Et2Mg(tmeda) (R = Me, Et) reacts with phenylacetylene to produce [Mg2Et(phenylethynyl)3-(tmeda)]2 benzene 46 (Figure 22).170 Related to that of alkali metal alkynyl magnesates, the structure of 46 is... 

Although reports on silver(i) cr-alkynyl complexes have appeared for more than a century, the number of examples was still very limited prior to the past decade, and many of them were referred to as insoluble homoleptic polymeric [Ag(C=CR)]oo. Molecular alkynylsilver(i) complexes were often heteroleptic in nature and were achieved commonly through the stabilization by an extra coordination with strong cr-donor ligands such as amines, phosphines, and arsines. 

An alternative method of modifying proteins to contain alkynyl groups is to use the propargyl-PEGj-NHS ester compound described in Chapter 18, Section 2. This reagent will react spontaneously with available amine groups in proteins to form an amide bond without the need to use EDC, as in the following protocol. 

Figure 17.15 The small carboxylate-alkyne compound 4-pentynoic acid can be used to modify proteins at their amine groups with EDC to provide alkyne sites for click chemistry-mediated conjugation. The subsequent reaction of an azido-PEG-modified gold nanoparticle with the alkynyl-protein in the presence of Cu1+ yields the triazole-coupled protein.

Dieter developed a flexible two step synthesis of substituted pyrroles involving initial Beak deprotonation of /ert-butoxycarbonyl (Boc) amines 36 followed by addition of CuX-2LiCl (X = -Cl, -CN) to afford a-aminoalkylcuprates. Such cuprates undergo conjugate addition reactions to a,(3-alkynyl ketones affording a,(3-enones 37, which upon treatment with PhOH/TMSCl undergo carbamate deprotection and intramolecular cyclization to afford the pyrroles 38 . 

The Sonogashira reaction is of considerable value in heterocyclic synthesis. It has been conducted on the pyrazine ring of quinoxaline and the resulting alkynyl- and dialkynyl-quinoxalines were subsequently utilized to synthesize condensed quinoxalines [52-55], Ames et al. prepared unsymmetrical diynes from 2,3-dichloroquinoxalines. Thus, condensation of 2-chloroquinoxaline (93) with an excess of phenylacetylene furnished 2-phenylethynylquinoxaline (94). Displacement of the chloride with the amine also occurred when the condensation was carried out in the presence of diethylamine. Treatment of 94 with a large excess of aqueous dimethylamine led to ketone 95 that exists predominantly in the intramolecularly hydrogen-bonded enol form 96. 

Carbonylation reactions under water-gas-shift conditions have been largely explored, alkynols giving saturated lactones and alkynyl amines giving saturated lactams [43]. Intramolecular alkoxycarbonylations of alkynols producing unsaturated lactones will be further described in the following paragraph. 

Additionally, dimedone derivative 241 and propargylamine 234 could be combined to give the alkynyl vinyl amine 242. The rearrangement/cyclization cascade could be induced upon heating until reflux in chlorobenzene. The an-... 

Addition to linear 1,1-disubstituted allylic acetates is slower than addition to monosubstituted allylic esters. Additions to allylic trifluoroacetates or phosphates are faster than additions to allylic carbonates or acetates, and reactions of branched allylic esters are faster than additions to linear allylic esters. Aryl-, vinyl, alkynyl, and alkyl-substituted allylic esters readily undergo allylic substitution. Amines and stabilized enolates both react with these electrophiles in the presence of the catalyst generated from an iridium precursor and triphenylphosphite. 

Although the CuBr/QUINAP system is an effective chiral catalyst in alkynylation of imines or iminiums, one drawback is that enantiopure QUINAP is quite expensive. An analog of QUINAP, PINAP (Figure 5.2), was readily synthesized and found as a very effective chiral ligand in the direct addition of alkynes to iminiums generated from aldehydes and secondary amines in situ (Scheme 5.8). ... 

Other Systems In contrast to the highly successful alkynylation of imines, copper catalysts failed in the asymmetric alkynylation of aldehydes. On the other hand, the combination of various Uewis acids and chiral amines were studied extensively to... 

Scheme 5.6. Asymmetric alkynylation of iminiums generated from aldehydes and amines.

In addition, iodine snccessfnlly catalyzed the electrophilic snbstitntion reaction of indoles with aldehydes and ketones to bis(indonyl)methanes [225], the deprotection of aromatic acetates [226], esterifications [227], transesterifications [227], the chemoselective thioacetalization of carbon functions [228], the addition of mercaptans to a,P-nnsatnrated carboxylic acids [229], the imino-Diels-Alder reaction [230], the synthesis of iV-Boc protected amines [231], the preparation of alkynyl sngars from D-glycals [232], the preparation of methyl bisnlfate [233], and the synthesis of P-acetamido ketones from aromatic aldehydes, enolizable ketones or ketoesters and acetonitrile [234],... 

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