Cp2ZrCl2-Catalyzed cycloalumination of acetylenic alcohols and propargylamines by Et3Al

Abstract

The Cp 2 ZrCl 2 catalyzed cycloalumination of acetylenic alcohols and propargylamines by Et 3 Al was studied. The process affords 2,3 disubstituted alumacyclopent 2 enes, which were identified by the analysis of the products of their deuterolysis and hydrolysis. The cycloalumi nation of alkyl and phenyl substituted propargylamines proceeds with high regio and stereo selectivity to give the corresponding allylamine derivatives in high yield. Unlike the phenyl derivatives, the cycloalumination of alkyl substituted acetylenic alcohols (propargyl, homopro pargyl, and bishomopropargyl alcohols) is not regioselective.Among numerous methods of synthesis of organoalu minum compounds, the reactions of hydro , carbo , and cycloalumination of olefins and acetylenes found the wid est use. 1 However, the first two methods are well studied both methodologically and theoretically, while cycloalu mination is relatively new promising direction that re quires the study of boundaries of application of this reac tion and its mechanism. We have earlier 2 reported the synthesis of substituted alumacyclopent 2 enes from alkyl and phenyl substituted acetylenes. It was found 3 that the cycloalumination of nonsymmetric alkyl , phenyl , and allyl substituted acetylenes by Et 3 Al affords regioisomeric 2,3 disubstituted alumacyclopent 2 enes, whose yield and ratio depend on the nature of substituents in the starting acetylenes.In order to extend the area of application of the above cycloalumination reaction and taking into account the important role of various functional substituents in the induction of biological activity, in the present work we studied the regularities of the reaction with acetylenic alcohols and amines. Results and DiscussionCycloalumination of propargyl alcohols. At room tem perature propargyl alcohols are not almost involved in cycloalumination. For instance, in the reaction of hept 2 ynol with Et 3 Al (the mole ratio of the reactants is 1 : 3) in hexane in the presence of 10 mol.% Cp 2 ZrCl 2 at room temperature, the conversion of the starting propargyl alcohol after 24 h does not exceed 5%. However, the rise of the reaction temperature to 40 °С and an increase in the catalyst concentration to 20 mol.% favor the formation of alumacyclopent 2 enes. In the case of alkyl substituted propargyl alcohols (hept 2 ynol, non 2 ynol), cycloalu mination followed by deuterolysis affords deuterolysis products 1a,b in 37 and 41% yields, respectively (Scheme 1). The reaction occurs stereoselectively to form substituted allyl alcohols of the Z configuration. The cycloalumina tion of 3 phenylprop 2 ynol requires more rigid condi tions and the use of 3 molar equivalents of Et 3 Al over propargyl alcohol. However, the reaction product is formed with high regio and stereoselectivity and in a higher yield (60%) compared to alkyl substituted propargyl alcohols. Scheme 1 R = Bu (1a), C 6 H 13 (1b, 2a), Ph (1c, 2b)

NbCl5-Mg Reagent System in Regio- and Stereoselective Synthesis of (2Z)-Alkenylamines and (3Z)-Alkenylols from Substituted 2-Alkynylamines and 3-Alkynylols

“…Apparently, in the case of propargylic alcohols, the formation of high-molecular-weight compounds is attributed to the polymerization of niobium-containing allene, which is generated via the β-elimination of the alkoxide group of the niobiacyclopropene intermediate. Previously, we have found that the Zr-catalyzed cycloalumination of substituted propargylic alcohols was also accompanied by the polymerization as the side reaction caused by the β-elimination of the alkoxide group [ 56 ]. However, the reaction of substituted homopropargylic alcohols 4 with four equiv.…”

2-Zincoethylzincation of 2-Alkynylamines and 1-Alkynylphosphines Catalyzed by Titanium(IV) Isopropoxide and Ethylmagnesium Bromide

“…strates that αor β-heteroatom-substituted alkynes react much more promptly than internal aliphatic alkynes, and thus enhances significantly the synthetic scope of the transformation by disclosing an efficient access to some heteroatom-functionalized alkenes with control of the double-bond geometry. The study represents an improvement over previous works on Zr-catalyzed cycloalumination of propargylamines 21 and alkynylphosphines 22 because the current catalytic system consisting of Et 2 Zn, Ti(O-iPr) 4 , and EtMgBr is more practical and less costly. Moreover, the dizincated species offer more potential for subsequent functionalization than the dialuminated species.…”

“…Meanwhile, it is known that 1-alkynylphosphines, 1-alkynylphosphonates, propargylamines, 1-alkynyl selenides, and 1-alkynyl sulfides are efficient substrates for the preparation of zirconacyclopentenes [17][18][19][20] and aluminacyclopentenes. [21][22][23][24] Regarding 2-zincoethylzincation, only one case of the preparation of organozinc derivative in 63% yield only after 4 days using the Ti-Mg-catalyzed reaction of 5decyne with Et 2 Zn has been reported in the literature. 25 However, this reaction is a unique example of carbozincation of the triple carbon-carbon bond with Et 2 Zn using oxidative coupling of ethylene and 5-decyne on titanium(II) in catalytic cycle.…”

Zirconium-Catalyzed Alkyne Carbo- and Cycloalumination Reactions in Stereoselective Preparation of 1-Alkenyl Selenides

“…46 Generally, it is consistent with our earlier views about the key role of zirconocene-ethylene intermediate in this reaction. 47 While considering the Zr-catalyzed reaction of Et 3 Al with propargyl alcohols, propargylamines, 37 and 1-alkynylphosphines, 38 we suggested that the Et 2 AlCl molecule located in the zirconacyclopropene coordination sphere is the principal factor determining the regioselectivity of cycloalumination. Similarly, in the case of cycloalumination of 1-alkynyl selenides, one can assume the formation of stable five-membered cyclic complex (Scheme 2).…”

“…33,34 Successful results on the selenation of cyclododecyne and cyclododeca-1,5-diyne cycloalumination products with selenium at elevated temperature have been reported. 35,36 As an alternative, recently we developed regio-and stereoselective methods for the preparation of О-, N-, and P-containing alkenes by Cp 2 ZrCl 2catalyzed cycloalumination of propargyl and homopropargyl alcohols, propargylamines, 37 and 1-alkynylphosphines. 38 The efficiency of carboalumination for the synthesis of P-and S-containing alkenes was demonstrated by Cp 2 ZrCl 2 -catalyzed ethylalumination of 1-alkynyl phosphorus oxides 39 and methylalumination of alkynyl sulfones, sulfoxides, and sulfides.…”