TMS-acetylene

Furthermore, when trimethylsilylacetylene 40 was used as an alkyne in the [IrCl(cod)]2-catalyzed reaction, propargyUc amines (where the alkyne was added to the double bond of imine) were obtained (Equation 10.7) [21, 23]. It is probable that the reaction proceeds through oxidative addition of the terminal C—H bond of alkyne to the Ir complex, followed by the insertion of imine to the resulting Ir-H complex. The crosscoupling reachon of trimethylsilyl (TMS)-acetylene with aldimines took place by [IrCl(cod)]2, leading to the corresponding adducts (Equahon 10.8) [24]. 

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 TMS-acetylene (0.10 mol) is added to a solution of 6 g of KOH in 40 ml of methanol and the mixture is heated for 30 min at 60 C. If the b.p. of the acetylene ROCH is higher than 60 C/10 mmHg, the greater part of the methanol can be removed under reduced pressure (rotary evaporator). After addition of a sufficient amount of water, the acetylene is extracted with Et20 or pentane. In the cases of more volatile acetylenes, the reaction mixture is poured into 300 ml of water, after which extraction with Et20 Or pentane is carried out. 

Nolan and co-workers reported on the coupling of arylbromides with TMS acetylenes making use of the imidazolium salt 34 in combination with Pd(OAc)2 and Cul. Slightly lower yields were obtained in the absence of the copper salt. Ag20 and Agl, instead of copper salts, have also been used with Pd(PPh3)4 for the coupling of aryl iodides with bis(TMS)alkynes and the coupling of vinyltriflates with a variety of alkynylsilanes, respectively. 

Normant and Poisson prepared allenylzinc bromide reagents from TMS acetylenes along the lines of Epsztein and coworkers5, by sequential lithiation with s-BuLi to yield a lithiated species, and subsequent transmetallation with ZnBr2 (equation 35)27,28. Additions to racemic /J-silyloxy aldehydes proceed with low diastereoselectivity to afford mixtures of the anti,anti and anti,syn adducts (Table 17). The latter adducts are formed via an anti Felkin-Anh transition state. Additions to the racemic IV-benzylimine analogs, on the other hand, proceed with nearly complete Felkin-Anh diastereoselectivity to yield the anti,anti amino alcohol adducts (Table 18). 

Equally, in presence of A1C13, if N,N-diethyl-carbamoyl chloride is applied to an l-alkyl-2-TMS-acetylene, the corresponding propargylic acid amide 56 can be isolated52 (see Scheme 6). 

Concluding this part it must be stated that the addition of 11 across the carbonyl moiety in presence of quaternary ammonium fluorides has been achieved179. Benzaldehyde (242) and phenyl-TMS-acetylene (11) form (a-trimethylsiloxybenzyl)-phenylacetylene (259). 

As acetylene components, bis-TMS-acetylene (12), phenyl-TMS-acetylene (11), mono- TMS-acetylene (7) and TMS-acetyl-acetylene (317) were applied to diazomethane (318) and ethyl diazoacetate (319) giving the products 320-325 and 326, respectively. If 320 is treated with bromine, the corresponding monobromo- (328) and di-... 

McDonald performed an asymmetric synthesis of D-desosamine, with high selectivity, by diastereoselective addition of TMS-acetylene to an a-unbranched aldehyde obtaining the propargylic alcohol [23]. The reaction proceeded in nearly 100 % diastereoselectivity albeit in moderate (60 %) yield (Eq. 19). 

Reagents (i) TMS-acetylene, Pd(PPh3)2CI2, Cu, Et3N, dioxane (ii) allylic halide, K2C03, DMF (iii) Co2(CO)8 then heat or NMO... 

Prior to our studies trimethylsilyl (TMS) acetylene (4a) has turned out to be a notorious problem in standard acid chloride couplings and there was no report on its successful transformation. We have optimized the coupling conditions and we exemplified them for several (hetero)aroyl chlorides 7 as coupling partners (Scheme 6). It is noteworthy to mention that the yields for the corresponding Stille couplings with tributylstannyl TMS acetylene as alkyne coupling partner give with 70% (8a) [49], 51% (8b) [50], and 45% (8c) [51] substantially lower yields. 

Iodoimidazole 371 coupled efficiently with TMS-acetylene 379 to produce 2-alkynyl-imidazole 380 in the presence of Cul and PdCl2(PPh3)2 at only 35 °C (Scheme 90) <2006JA4119>. 

On heating the 2-yS-azidomethyl penam sulphone (85) with suitable acetylenes, a series of 2-/S-(l,2,3-triazolyl)methyl penam sulphone esters was obtained, which upon deprotection gave the free acids (86) [48, 49]. In particular, reaction of (85) with either vinyl acetate or (trimethylsi-lyl)acetylene provided the parent triazole, tazobactam (30), after hydrogenation (and prior potassium fluoride-18-crown-6 treatment in the case of the TMS acetylene) [50]. 

The concise formal total synthesis of mappicine was accomplished using an intramolecular hetero Diels-Alder reaction as the key step by M. lhara and co-workers. Introduction of the necessary acetylenic moiety at the C2 position was achieved by the Sonogashira cross-coupling of a 2-chloroquinoline derivative with TMS-acetylene. Several substituents at the C3 position were investigated, and it was found that the unprotected hydroxymethyl substituent gave almost quantitative yield of the desired disubstituted alkyne product. 

Very electron-deficient TMS acetylenes such as eynones are unstable and lose the TMS group upon stirring in MeOH. ... 

A common approach is the reaction of halogenoalkylsilanes with alkali metal (lithium, sodium)110,111 or magnesium (Grignard)112 derivatives of acetylene to form silylated acetylenes which can be illustrated by the synthesis of TMS-acetylenes (182/57a) (equation 84). The reaction can be slightly modified by using bis(TMS)-sulfate (184) as silylating agent (equation 85)113. 

When allene (200) is treated with two equivalents of butyllithium and of Me3SiCl 196 (R = H) is formed (equation 94)119a. If TMS-acetylene (57a) reacts with ethylmagnesium bromide in the presence of N,iV-dimethyl formamide, 3-TMS-propynal (201) can be isolated (69% yield) which can form 2-TMS-ethynyl-l,3-dioxane (202) with 1,3-propa-nediol in 81% yield (equation 95)120. 

Ethyl 3-TMS-2-propynoate (204) is formed by the reaction of TMS-acetylene (57a) with butyllithium and subsequent treatment with triethoxycarbenium tetrafluoroborate and hydrolysis (equation 96)121. If bis(TMS)-acetylene (189) is employed with acyl halides or acid anhydrides in the presence of a Lewis acid (e.g. A1C13) as a catalyst, then... 

By means of the CuCl-TMEDA complex as a catalyst one can synthesize 1,4-bis(TMS)-l,3-butadiyne (207) from TMS-acetylene (57a) in the presence of oxygen (equation 98)123. Alternatively, 207 and the corresponding TES-compound (210), respectively, can be formed by the reaction of 16 or the corresponding TES-C1 (209) with the di-Grignard derivative of 1,3-butadiyne (208) (equation 99)124 125. 

A well-established pathway for the synthesis of silylated heteroarenes is the 1,3-dipolarophilic cycloaddition of alkynylsilanes (97a/189) with diazo compounds (261) or (262). Thus, TMS-phenylacetylene (97a) and diazomethane (261) form 3-TMS-4-phenylpyrazole (263), whereas bis(TMS)-acetylene (189) and 261 afford 3,4-bis-(TMS)-pyrazole (264). Ethyl diazoacetate (262) plus 189 give rise to 3,4-bis(TMS)-5-ethoxycarbonylpyrazole (265) in good yields (equation 121)151. The sterospecific formation of 263 via 1,3-dipolarophilic cycloaddition from 97a and 261 can be considered as... 

For the synthesis of tris (TMS)-ketimine (448), acetonitrile (386a) is lithiated with t-butyllithium and then converted into 448 as a by-product [bis(TMS)amino]-TMS-acetylene (449) occurs (equation 208)228. In addition, tris(TMS)-ketimine (448) can be... 

An interesting reaction is the addition of l-phenyl-2-TMS-acetylene to carbonyl compounds, e.g. cyclohexanone (113) in the presence of catalytic amounts of tetrabutyl-ammoniumfluoride to form, for instance, [l-(phenylethynyl)cyclohex-l-yloxy]tri-methylsilane (569) (equation 287)324. However, if 4-t-butylcyclohexanone (570) reacts... 

The (o-aminoaryl)acetylenes 27 are easily accessible by Pd-mediated SONOGASHIRA cross coupling reactions of (o-halogeno)aniline derivatives 26 (X preferably I) with terminal acetylenes. Alternatively, 27 is prepared by Sonogashira coupling of 26 with TMS-acetylene (to give 29), desilylation of 29 and base-induced alkylation at the free acetylene terminus (29 29a -> 27). 

Scheme 17 Cross-coupling of aryl halides and TMS-acetylenes mediated by in situ generated Pd/NHC system...

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