Silylative coupling allylsilanes

Titanium(IV) is a powerful but selective Lewis acid which can promote the coupling of allylsilanes with carbonyl compounds and derivatives In the presence of titanium tetrachlonde, benzalacetone reacts with allyltnmethylsilane by 1,4-addition to give 4-PHENYL-6-HEPTEN-2-ONE. Similarly, the enol silyl ether of cyclopentanone is coupled with f-pentyl chloride using titanium tetrachlonde to give 2-(tert-PENTYL)CYCLOPENTANONE, an example of a-tert-alkylation of ketones. 

Optically active (Z)-l-substituted-2-alkenylsilanes are also available by asymmetric cross coupling, and similarly react with aldehydes in the presence of titanium(IV) chloride by an SE process in which the electrophile attacks the allylsilane double bond unit with respect to the leaving silyl group to form ( )-s)vr-products. However the enantiomeric excesses of these (Z)-allylsilanes tend to be lower than those of their ( )-isomers, and their reactions with aldehydes tend to be less stereoselective with more of the (E)-anti products being obtained74. 

Schafer reported that the electrochemical oxidation of silyl enol ethers results in the homo-coupling products. 1,4-diketones (Scheme 25) [59], A mechanism involving the dimerization of initially formed cation radical species seems to be reasonable. Another possible mechanism involves the decomposition of the cation radical by Si-O bond cleavage to give the radical species which dimerizes to form the 1,4-diketone. In the case of the anodic oxidation of allylsilanes and benzylsilanes, the radical intermediate is immediately oxidized to give the cationic species, because oxidation potentials of allyl radicals and benzyl radicals are relatively low. But in the case of a-oxoalkyl radicals, the oxidation to the cationic species seems to be retarded. Presumably, the oxidation potential of such radicals becomes more positive because of the electron-withdrawing effect of the carbonyl group. Therefore, the dimerization seems to take place preferentially. 

The alkoxycarbenium ions generated by the cation pool method react with various carbon nucleophiles such as substituted allylsilanes and enol silyl ethers to give the corresponding coupling products in good yields. It should be noted that the reactions of alkoxycarbenium ion pools with such nucleophiles are much faster than the Lewis acid promoted reactions of acetals with similar nucleophiles. A higher concentration of the cationic species in the cation pool method seems to be responsible. 

Further investigations are needed to establish, whether this approach is really useful to obtain chiral allylsilanes 2, which are synthetically quite interesting intermediates. They are available otherwise only by asymmetric cross-coupling of silyl alkyl Grignard reagents with bromoethylenes in the presence of a chiral ferrocenylphosphine-palladium catalyst54. 

The cross-coupling route to allylsilanes is effective with either aromatic or aliphatic a-silylated Grignard reagents16, and palladium catalysts are more reactive and stereoselective than the corresponding nickel complexes. Unsubstituted or i+monosubstituted alkenyl bromides work well but the Z-substituted bromides give lower yields and an inferior enantiomeric excess. The enantiomeric excess increases quite markedly with decreasing temperature, and optimum results are obtained at 0 C or below. 

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. 

Benzylic silyl ethers couple with allylsilanes in the presence of trityl tetrakis [3,5-bis(trifluoromethyl)phenyl]borate (TFPB) catalyst leading to carbon-carbon bond formation (equation 77). The corresponding Z11CI2-catalyzed reactions with an allyl silyl ether lead to a mixture of regioisomers145,146. 

Silyl enol ethers undergo cross-coupling with allylsilane in the presence of a Lewis acid. For example, an oxovanadium(V) complex can induce such condensation reactions (equation 81)150. 

The cross-coupling of allylsilanes with alkenes [50] and styrene [58] also occurs via their preliminary isomerization followed by the reaction of 1-propenylsilane with exemplary olefin-l-decene resulting in l-(triethoxysilyl)-1-decene as a product (Eq. 31). If the cross-coupling takes place, an expected product of this reaction is l-silyl-2-undecene, which is not detected. 

As we mentioned before, a classical Grignard reaction is formally described by the coupling of a covalent (albeit polarized) electrophile with an anionic nucleophile. Reactions shown in Scheme 2.41 (opposite) exemplify the alternative approach involving an interaction between cationic intermediates generated from carbonyl compounds (or their derivatives) under the action of Lewis acids and a purely covalent nucleophile, an allylsilane such as I09a or 109b. Similar electrophiles used in reactions with covalent silyl enolates such as 110 result in the formation of the aldol-Iike products (the Mukaiyama reaction ). 

Both silyl enolates and allylsilanes are excellent nucleophiles for alkylation by other stabilized carbocations such as the tertiary alkyl cations 111 or 112 (Scheme 2.42). Similarly, Michael-like additions, for example, the coupling of 113 with silyl ketene acetal 114, can be also achieved.Owing to the high electrophilicty of the enone system, this reaction proceeds smoothly in polar solvents, even in the absence of Lewis acids. 

The key element of this protocol is the initial addition of cationic electrophiles such as rerr-alkyl or acyl cations to the double bond of a DCHC complex of the conjugated enyne 118, which results in the formation of the substituted propargylic cation intermediate 119, Subsequent reaction with pre-selected external nucleophiles, for example allylsilanes or silyl enol ethers, leads to the formation of the final adducts 120. The reaction is carried out as a one-pot, three-component coupling and can be used for the creation of two novel C-C bonds. It is a process somewhat complementary to the stepwise Michael addition described earlier (Scheme 2.31), with a reverse order of E and Nu addition. Oxidative decomplexation of 120 yields the product 121. The overall... 

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. 

The coupling of an allyl or acyl moiety onto carbon atoms is achieved by anodic oxidation of a-heteroatom substituted organostannanes or Oj -acetals in the presence of allylsilanes or silyl enol ethers. The reaction probably involves carbocations as intermediates that undergo electrophilic addition to the double bond [245c]. 

Cross-coupling of enol silyl ethers with primary alkyl Grignard reagents is also catalyzed by Ni complexes, as exemplified by the conversion of an enol silyl ether into an allylsilane (equation 54) and by stereoselective alkylation (equation 55). ... 

For example, the anodic oxidation of a silyl-substituted carbamate to generate a solution of N-acyliminium ion and the cathodic reduction of cinnamyl chloride in the presence of chlorotrimethylsilane to generate the corresponding allylsilane can be carried out simultaneously in a single electrochemical microflow cell under continuous flow conditions (Figure 5.10). The N-acyliminium ion, the anodic product, is allowed to react with the allylsilane, the cathodic product, to give the coupling product. 

The asymmetric cross-coupling was successfully applied to the synthesis of optically active allylsilanes [50,51] (Scheme 10). The reactions of a-(trimethyl-silyl)benzylmagnesium bromide (49) with vinyl bromide (4b), (E)-bromopro-pene (( )-50), and (R)-bromostyrene E)-8) in the presence of 0.5 mol % of a palladium complex coordinated with chiral ferrocenylphosphine, (R)-(S)-PPFA (10a), gave the corresponding (R)-allylsilanes (51) with 95%, 85%, and 95% ee, respectively, which were substituted with phenyl group at the chiral carbon center bonded to the siHcon atom. These allylsilanes were used for the S. ... 

Allylsilanes are prepared from allyl ethers (silyl ethers or phenyl ethers) and RsSiCl coupling takes place in the presence of Pd(acac)2 and PhMgBr (240 mol%). ... 

Oxidative cross-coupling. a-Stannylalkanoic esters and amides undergo oxidation, and the resulting free radicals can be trapped in situ by electron-rich alkenes such as silyl enol ethers and allylsilanes. Thus y-keto esters are accessible by this reaction. Note that a-germanylalkanoic esters are less reactive toward the oxidant and the a-silylalkanoic esters do not undergo oxidation at all. 

Most interestingly, allylsilanes, stannanes, and silyl enolethers function as nucleophiles in the reactions described here and are subject to the same stereochemical preferences as alcohols [148, 149]. Thus, unselective reactions are observed with a per-O-benzyl mannopyranosyl donor, p-selective couplings are seen with a 4,6-0-benzylidene protected mannopyranosyl donor, and ot-selective reactions with the corresponding glucopyranosyl donor (Scheme 46). 

Silyl enol ethers are shown to have nucleophilicity between that of allylsilanes and aliylstannanes, and siloxyallyl barium reagents couple RCHO and RX at the y-position. ... 

Palladium-catalyzed coupling of the silyl bromide to the terminal alkyne (10) gives the propargylic allylsilane (11), which is a key intermediate in the synthesis of a 10-membered cyclodiynol analog (12) of the antitumor agent neocarzinostatin (eq 19). ... 

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