Cross-coupling-cyclocondensation

As a consequence of the mild reaction conditions in the sequence to 3-halo furans 55 the palladium catalyst should be still intact to trigger another Pd-catalyzed coupling in the sense of a sequentially Pd-catalyzed process [31]. As a consequence, a sequential Sonogashira-deprotection-addition-cyclocondensation-Suzuki reaction, where the same catalyst system is applied in two consecutive significantly different cross-coupling reactions in the same reaction vessel should be feasible. Therefore, upon consecutive reactions of (hetero)aroyl chlorides 7 and THP-protected propargyl alcohols 54, Nal and PTSA, and finally, addition of 1.05 equiv of boronic acids 60 and sodium carbonate, the substituted 3-aryl furans 61 can be obtained in decent yields (Scheme 35). 

A convenient and effective palladium-catalysed Suzuki-Miyaura cross coupling reaction of deactivated aryl chlorides with phenylboronic acid utilised the 1,3-diazepinium salts 107 as in situ precursors of the palladium ligands. These salts were prepared from the diamines 106 and cyclocondensation with triethyl orthoformate <05SL2394>. 

Trisubstituted isoxazoles 14 with ferrocenyl groups in 4- and 5-position can be synthesized utilizing acid chlorides 4, terminal alkynes 5, and hydroximinoyl chlorides 13 in a sequence consisting of modified Sonoga-shira cross-coupling I and cyclocondensation. Hydroximinoyl chlorides 13 are employed as synthetic equivalents of the corresponding aromatic nitrile... 

A different route to the intermediary Michael acceptor was used in the synthesis of 3-(hetero)aryl-lH-pyrazoles 28. In contrast to previously described approaches, the terminal alkyne, namely propynal diethylacetal (5d), was utilized to introduce the carbonyl group. Propynal diethylacetal (5d) acts as a synthetic equivalent of propargyl aldehyde and, thus, Sonoga-shira cross-coupling of (hetero)aryl iodides 6 and propynal diethylacetal (5d) and subsequent acetal cleavage and concomitant cyclocondensation in the presence of para-toluenesulfonic acid and hydrazine hydrochloride (20a) furnishes the title compounds (Scheme 15) (201 lMOM(l6)9340). 

Lewis acid promoted reactions of silicon enolates, /.e., silyl enol ethers and ketene silyl acetals with various electrophiles have yielded a wealth of novel and selective synthetic methods. This combination of reagents has been used in the past to perform such reactions as aldol-condensations with aldehydes and acetals, imine-condensations, conjugate additions to a,P-enones, alkylations, electrophilic aminations, and Diels-Alder/cyclocondensations. Our own interest in this field has involved the use of titanium tetrachloride to promote the reaction of ketene silyl acetals with non-activated imines as an efficient route to P-lactams. This reaction has been applied to the asymmetric synthesis of P-lactams via a chiral imine-titanium tetrachloride template. We have also found that both ketene silyl acetals and vinylketene silyl acetals oxidativelly dimerize or cross-couple, in the presence of titanium tetrachloride to conveniently yield various diesters . Our present study concerns reactions of vinylketene silyl acetals with non-activated imines and vinylimines promoted by titanium and zirconium tetrachlorides. 

Keywords Quinoline Cyclocondensation Nucleophilic substitution of fluorine atom Cross-coupling reactions Antibacterial activity Enzyme inhibitor... 

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