One-Pot Synthesis of 3-(Trimethylsilyl)propynamides

Abstract

A highly efficient one-pot procedure was developed for the synthesis of 3-trimethylsilylpropynamides by acylation of amines with trimethylsilylpropynoyl chloride generated in situ. Selective N-acylation and N,O-bis-acylation of β-amino alcohols with formation of, respectively, N-(hydroxyalkyl)propynamides and 2-methyl-2-[3-(trimethylsilyl)propynoylamino]propyl 3-(trimethylsilyl)propynoate were accomplished with high yields. 3-(Trimethylsilyl)propynoic acid amides are valuable intermediates in the synthesis of biologically important heterocyclic compounds, such as chiral 2-trimethylsilyldihydro-1,3-oxazoles [1], trimethylsilylidenehydantoins [2], 1,5-trisubstituted 1H-1,2,3-triazoles [3], indoloquinolines [key compounds in the total synthesis of alkaloids (±)-lysergic acid and (±)-LSD] [4], as well as in the regio-and stereocontrolled synthesis of 3-carbamoylcyclopentenones as chiral synthetic intermediates or ligands [5], tetra-(hexa)hydrofuro[3,4-e]isoindol-6-ones as intermediate products in the synthesis of antibiotic lactonamycin [6], and unsaturated γ-[7] and δ-lactams [8].

(Z,Z)-Selanediylbis(2-propenamides): Novel Class of Organoselenium Compounds with High Glutathione Peroxidase-Like Activity. Regio- and Stereoselective Reaction of Sodium Selenide with 3-Trimethylsilyl-2-propynamides

“…Their preparation is usually based on toxic and skin-irritating propynoic acid. The silylpropynamides 1a – i were synthesized in the present work by the method depicted in Scheme 4 [ 61 , 62 , 63 ]. Inexpensive starting propargyl alcohol, good selectivity of these reactions and high yield of the target products allowed to make silylpropynamides 1a – i readily available compounds and to use them in the synthesis of valuable products [ 64 , 65 , 66 ].…”

Silica Gel as a Promoter of Sequential Aza‐Michael/Michael Reactions of Amines and Propiolic Esters: Solvent‐ and Metal‐Free Synthesis of Polyfunctionalized Conjugated Dienes

“…In method C, chemoselectivity is excellent when aliphatic amines are used as substrates because all byproducts are formed in yields of 6%.I ti sw orse, but still satisfactory, with aromatic amines:a part from two cases (amines 1p and 1s), the diene is the main product in all reactions and its yield exceeds that of 5 and 5',f rom 18 %t op ure diene.T his is of particular importance because, to date, method Cr epresents the only way to obtain functionalized conjugated dienes 4 from an aromatic amine and propiolic ester in satisfactory yields and in ar easonable time, as shown by the results in Figure 1a nd the literature data in the Introduction section. [20] No propiolic amide was detected as ab yproduct in any of the performed reactions, which suggested that 1,4-addition of an amine to the propiolic ester is the much more favored pathway under the conditions in methods A, B, and C. In fact, synthesis of ap ropiolic amide, if carried out from an ester,r equiresv ery low temperatures( À30-À78 8C) to favor 1,2-over 1,4-addition, [21] or formation of an activated intermediate, such as propiolyl chloride, [22] anhydride, [23] activated ester (N-hydroxysuccinimideester), [23] or the use of enzymes. [24] The scope of method Cw as furthert ested by varying the ester component that involved n-butyl,allyl, benzyl, cyclohexyl, and phenylp ropiolate 2b-f,f our of which are commercially available.…”

Highly efficient desilylation of 3-trimethylsilylprop-2-ynamides by the action of KF-Al2O3

“…Microwave-assisted reactions were performed in a 25-ml Teflon high-pressure reactor using an unmodified LG MS-1904H microwave furnace (700 W). Initial 3-trimethylsilylprop-2-ynamides were synthesized according to the procedure reported in [24]; KF-Al 2 O 3 (KF concentration 40%) was prepared as described in [25].…”

“…To conclude, we have developed a simple and highly efficient procedure for the synthesis of terminal propynamides from accessible 3-trimethylsilylprop-2-ynamides [22,24] using a catalytic amount of KFAl 2 O 3 . Conditions have been found for selective onestep preparation of new mono-and dialkoxy amides as polyfunctional intermediate products for organic synthesis.…”