Allylsilanes coupling reactions

The intramolecular coupling of enolethers with enolethers, styrenes, alkyl-substituted olefins, allylsilanes, and vinylsilanes was systematically studied by Moeller [69]. Many of these coupling reactions turned out to be compatible with the smooth formation of quaternary carbon atoms (Eq. 11) [70], which were formed diastere-oselectively and led to fused bicyclic ring skeletons having a ds-stereochemistry [71]. The cyclization is compatible with acid-sensitive functional groups as the allylic alkoxy group. Moeller has demonstrated in some cases that these reactions can be run without loss of selectivity and yield in a simple beaker with either a carbon rod or reticulated carbon as anode without potential control and a 6-V lantern battery as power supply [71]. 

Allyl- and vinylsilane chemistry was one of the first areas of reagent synthesis impacted by CM methodology. Allylsilanes are commonly employed in nucleophilic additions to carbonyl compounds, epoxides, and Michael acceptors (the Sakurai reaction) vinylsilanes are useful reagents for palladium-coupling reactions. As the ubiquitous application of CM to this substrate class has recently been described in several excellent reviews, this topic will not be discussed in detail, with the exception of the use of silane moieties to direct CM stereoselectivity (previously discussed in Section 11.06.3.2). 

The coupling reaction of allylsilane with the w-thiomethoxyacetal is catalyzed by TMSOTf51. TiCLj-mediated reaction of a-bromoallylsilane 7 with 1,1-diethoxyethane leads to homoallylic ether 12 stereoselectively in excellent yield (equation 9)40. Under similar reaction conditions, double substitution of allylsilane to diketals 13 affords 14 in high diastereoselectivity (equation 10)52. 

The TiCU-induced three-component coupling reaction of an a-haloacylsilane, allylsilane and another carbonyl compound gives 48 in good yield. A silyl enol ether intermediate is suggested (equation 31)82. The reaction of a cyclopropyl ketone with allylsilane yields a mixture of skeletal rearranged products83. 

A three-component radical coupling reaction involving allylsilanes has been employed leading to 145 (equation 121)213. It is noteworthy that the corresponding carbon-silicon bond remains intact in this reaction. 

The direct substitution of hydroxyl groups can also be extended towards propargylic alcohols. In the presence of FeCl3, a plethora of O-, N- or S-nudeophiles are able to react with substituted propargylic alcohols [17]. Amongst the variety of nucleophiles, allylsilanes occupy an important position since this example resembles a cross-coupling reaction between an organometallic compound and an alcohol (Scheme 7.12) [17]. 

Marko et al. initially employed allylsilane 171 during their study on the scope and limitations of the IMSC methodology in 1993 [65] and expected to obtain the exo-methylene tetrahydrofurans 175 (Scheme 13.60). However, none of the desired furan derivatives 175 was obtained when a mixture of 171 and aldehydes 174 was treated with a range of Lewis acids. Rather, the diastereomerically pure exo-methylene tetrahydropyrans 173 were isolated, albeit in modest yields (Scheme 13.61). In 1995, Oriyama et al. [79] published the IMSC reaction of acetals with allylsilane 171, yielding the desired tetrahydrofurans 175 in the presence of the SnC /AcCl system (See Chapter 13.4.2). Interestingly, product 173 was not formed when the corresponding acetals were used instead of the aldehydes in this coupling reaction and vice-versa [49, 65]. 

Closer examination of tetrahydropyrans 173 clearly reveals that two molecules of aldehyde 174 have been appended onto allylsilane 171 via a novel three-component coupling reaction. Marko et al. proposed the mechanism depicted in Scheme 13.61 [65], Formation of heterocycles 173 is described as a sequence of two processes an initial ene-type reaction [80] which leads to alcohol 177 via the chair-like transition state 176, in which both the aldehydic R-group and the OTMS substituent assume an equatorial position. The high regio- and stereoselectivity observed in this ene-reaction can be nicely explained by considering the stabilizing /(-silicon effect and the repulsive 1,3-diaxial interactions. Transition state 176 contains no 1,3-diaxial interactions and benefits fully from the stabilizing /(-silicon effect [81, 82] (for more detailed transition-state discussion see ref. [63]). 

The ruthenium-catalyzed addition of C-H bonds in aromatic ketones to olefins can be applied to a variety of ketones, for example acetophenones, naphthyl ketones, and heteroaromatic ketones. Representative examples are shown in the Table 1. Terminal olefins such as vinylsilanes, allylsilanes, styrenes, tert-butylethy-lene, and 1-hexene are applicable to this C-H/olefin coupling reaction. Some internal olefins, for example cyclopentene and norbornene are effective in this alkylation. The reaction of 2-acetonaphthone 1 provides the 1-alkylation product 2 selectively. Alkylations of heteroaromatic ketones such as acyl thiophenes 3, acyl furans, and acyl pyrroles proceed with high yields. In the reaction of di- and tri-substitued aromatic ketones such as 4, which have two different ortho positions, C-C bond formation occurs at the less congested ortho position. Interestingly, in the reaction of m-methoxy- and m-fluoroacetophenones C-C bond formation occurs at the congested ortho position (2 -position). 

The kind of a fluoride ion activator and the leaving group in electrophiles affects the stereochemistry in the cross-coupling reaction of allylsilanes as exemplified with 2-cyclohexenyl(difluoro)phenylsilane (Eq. 31) 135]. 

It is a palladium-catalyzed cross-coupling reaction between organosilanes (vinyl, ethynyl and allylsilanes) and organic halides (aryl, vinyl and allyl halides). Allylpal-ladium chloride dimmer [( ri -C3H5PdCl)2] and either tris(diethylamino)sulfonium difluorotrimethylsilicate (TASF) or tetra-n-butylammonium fluoride (TBAF) are used as catalysts. Fluoride ion acts as an activator for the coupling, forming an intermediate hypervalent anionic silicon species, which can then transmetallate with palladium as a preliminary reaction to coupling. 

These have been much less popular, but some examples have been reported. These involve only alkenyltins containing one additional moiety on the G-carbon this substituent can be trimethylsilylmethyl (leading to functionalized allylsilanes [37] or divinyl ketones (Scheme 4-10) [38]) or trifluoromethyl [39]. The substituent can also be in the /3-position (E-geometry) examples have been reported by Parrain et al. [40] and Castano et al., the latter having used the coupling reaction of a jS-stannyl enone as the key step in the preparation of the indolizidine alkaloid ( )-monomorine here the coupling step is followed by an immediate in-situ reduction of the intermediate enone, the mechanism of which is unclear (Scheme 4-11) [41J. 

Scheme 10-9 Mechanism of regiochemical control for coupling reactions of allylsilanes.

Facile 6-elimination of the silyl group is also utilized in the intramolecular anodic olefin coupling reactions [159-161]. For example, the intramolecular anodic coupling of enol ether with allylsilane group has been reported [Eq. (44)]. This reaction seems to be quite useful for the construction of functionalized cyclic compounds because it leads to the regioselective formation of olefinic product via a facile 6-silyl elimination. 

Coupling reactions of alkyl Grignard reagents lacking -H substitution are exemplified by the stereoselective synthesis of a trideuteriomethylated alkene (equation 10) and of allylsilanes (equations 11 and 12). ° Cyclic bromoalkenes also undergo coupling smoothly (equation 13). ... 

In addition to Ni and Pd catalysts, Li2CuCU is also an effective catalyst for the coupling of alkenyl iodides with Grignard reagents. Since the stereochemistry of alkenyl iodides is also retained, the coupling reactions are useful for the stereoselective synthesis of disubstituted alkenes, - trisubstituted al-kenes, allylsilanes, allyl alcohols and tetrasubstituted alkenes (equations 25-29). ... 

In the presence of BFj, N-acylimines generated in situ from aldehydes or acetals and carbamates smoothly react with allylsilanes, propargylsilanes, and 2,4-pentadien-ylsilanes to give homoallyl [415], allenylmethyl [416], and 3,5-hexadienyl amines [417], respectively (Scheme 10.146). The three-component coupling reaction with crotyltrimethylsilane proceeds with moderate syn selectivity as in the crotylation of aldehydes [418]. 

A related coupling reaction is the condensation of aldehydes with alkyl trichlorotitanium compounds (RTiCl3). When methyltrichlorotitanium (MeTiCl3) was coupled with aldehyde 468 in dichloromethane at -78°C, a 91 9 mixture of 470/471 was formed via the chelated complex 469. Sakurai and co-worker had previously noted the coupling of allylsilanes to aldehydes in the presence of TiCl4.305... 

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