Acetylenes, reaction with trimethylsilyl

Potassium or lithium derivatives of ethyl acetate, dimethyl acetamide, acetonitrile, acetophenone, pinacolone and (trimethylsilyl)acetylene are known to undergo conjugate addition to 3-(t-butyldimethylsiloxy)-1 -cyclohexenyl t-butyl sulfone 328. The resulting a-sulfonyl carbanions 329 can be trapped stereospecifically by electrophiles such as water and methyl iodide417. When the nucleophile was an sp3-hybridized primary anion (Nu = CH2Y), the resulting product was mainly 330, while in the reaction with (trimethylsilyl)acetylide anion the main product was 331. 

Scheme 10.2 shows a protocol for synthesizing 1 and its further transformation into 4 [13a,d], Monolithiation of the diiodide 9 followed by treatment with S8 and AcCI generated 1. Next, a Sonogashira cross-coupling reaction with trimethylsilyl-acetylene afforded 10 in high yield. Desilylation was obtained upon treatment with n-Bu4NF, which provided the terminal alkyne 4. 

Silyl, germanyl and stannyl alk-l-ynyl ketones have been prepared from 2-lithio-2-(trimethylsilylethynyl)-l,3-dioxolane 448. The deprotonation of the dioxane 447 with n-BuLi at — 65 °C afforded the acyl anion 448 which, after reaction with trimethylsilyl, trimethylgermanyl and trimethylstannyl chloride, gave the expected derivatives (Scheme 117)658. Hydrolysis of these products with 0.01 M sulfuric acid at room temperature in aqueous acetone gave the corresponding acyl derivatives 449. On the other hand, the reaction of the intermediate 448 with alkyl halides allows the synthesis of acetylenic ketones659. 

Chiral dioxanones have also been employed as acetal auxiliaries in nucleophilic additions [33, 34]. Because of the inherent differences between carbox-ylates and alcoholates as leaving groups, it is the carboxylate that exclusively undergoes displacement. This was shown for the chiral l,3-dioxan-4-one 49 in its reaction with trimethylsilyl acetylene to give 50 in 99 1 dr (Equation 3)... 

Etherification. The reaction of alkyl haUdes with sugar polyols in the presence of aqueous alkaline reagents generally results in partial etherification. Thus, a tetraaHyl ether is formed on reaction of D-mannitol with aHyl bromide in the presence of 20% sodium hydroxide at 75°C (124). Treatment of this partial ether with metallic sodium to form an alcoholate, followed by reaction with additional aHyl bromide, leads to hexaaHyl D-mannitol (125). Complete methylation of D-mannitol occurs, however, by the action of dimethyl sulfate and sodium hydroxide (126). A mixture of tetra- and pentabutyloxymethyl ethers of D-mannitol results from the action of butyl chloromethyl ether (127). Completely substituted trimethylsilyl derivatives of polyols, distillable in vacuo, are prepared by interaction with trim ethyl chi oro s il an e in the presence of pyridine (128). Hexavinylmannitol is obtained from D-mannitol and acetylene at 25.31 MPa (250 atm) and 160°C (129). 

Free intermediate thioaldehydes 598 or 602 and the selenoaldehydes 605 and HMDSO 7 are obtained in THF at 0°C on treatment of aliphatic and aromatic aldehydes with bis(trimethylsilyl)thiane 601 or bis(trimethylsilyl)selenide 604 in the presence of traces of butyllithium, while trapping the sensitive intermediate thio- or selenoaldehydes 602 and 605 with cyclopentadiene or cyclohexadiene to furnish mixtures of endo and exo Diels-Alder adducts such as 603 a and 606 a and 603 b and 603 b [148-150], the exo/endo ratio of which can be controlled [150] (Scheme 5.48). Analogous reaction of ketones such as 2-adamantanone or acetylene ketones with MesSiXSiMes 608 (a. X=S (601) b. X=Se (604)) in the presence of... 

The reactions of complex 2a with ketones and aldehydes show a strong dependence on the substituents. With benzophenone, substitution of the silyl-substituted acetylene leads to the r]2-complex 58, which is additionally stabilized by a THF ligand. This complex can serve as an interesting starting material for other reactions. With benzaldehyde and acetophenone, the typical zirconadihydrofuran 59, akin to 2c, is obtained from a coupling reaction. This complex is unstable in the case of benzaldehyde and dimerizes, after elimination of bis(trimethylsilyl)acetylene, to yield 60. In this respect, it is similar to the above discussed complex 2c, since both of them show a tendency to eliminate the bis(trimethyl-silyl)acetylene. The reaction of methacrolein with complex 2a depends strongly on the solvent used [40]. 

Halopyridines, like simple carbocyclic aryl halides, are viable substrates for Pd-catalyzed crosscoupling reactions with terminal acetylenes in the presence of Pd/Cu catalyst. The Sonogashira reaction of 2,6-dibromopyridine with trimethylsilylacetylene afforded 2,6-bis(trimethylsilyl-ethynyl)pyridine (130), which was subsequently hydrolyzed with dilute alkali to provide an efficient access to 2,6-diethynylpyridine (131) [106]. Extensions of the reactions to 2-chloropyridine, 2-bromopyridine, and 3-bromopyridine were also successful albeit at elevated temperatures [107]. 

The palladium/copper-catalyzed coupling reaction of 2-iodo-3-methoxy-6-methylpyridine and terminal alkynes leads to the formation of o-methoxyalkynylpyridines which undergo electrophilic cyclization reactions to afford furo[3,2-3]pyridines in moderate yields <2005JOC10292>. A similar Pd/Cu-catalyzed reaction with hydroxypyridines and trimethylsilyl (TMS)-acetylene leads to the formation of alkynyl pyridines which cyclize to form furo[2,3- ]-pyridines in good yields <1998JME1357>. 

The reaction of trimethylsilylated terminal alkynes with iodoarenes can be performed under 1 atm CO pressure in the presence of dppf complex of palladium, and BU4NF at room temperature (Equation (23)). As trimethylsilyl derivatives of terminal acetylenes are known to undergo facile cleavage by fluoride ions, this reaction actually involves not the organosilicon compound, but acetylenide nucleophile. The method has been successfully applied to the modification of uracyl deoxynucleosides. 

Treating l-chloro-l-(trichlorovinyl)cyclopropanes with three equivalents of BuLi afforded the the dilithiated acetylene This, upon reaction with excess trimethylsilyl chloride, yielded the bis(trimethylsilyl)ethynylcyclopropane (equation 163). The same results can be achieved using magnesium metal in THF as the metallating agent, instead of the preferable BuLi236 238. 

Using the same boratabenzene 68, Bazan and co-workers have formed titanium complex 70 and then studied its further reactions with acetylenes. Treatment of 70 with acetylene itself resulted in 71 as well as two ring-expanded products, 72 and 73 (Scheme 1) <2003AGE4510>. Formation of 72 was favored at low concentrations of acetylene in toluene solution whereas 73 becomes prevalent at high concentrations a mechanism involving initial coordination of acetylene to titanium was proposed. Similar reaction of 70 with (trimethylsilyl)acetylene gave a 79% yield of the product analogous to 72, the structure of which was determined by X-ray diffraction (see Section 7.14.3). 

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