Allylating agents

Mg. Li and co-worker first reported magnesium-mediated Barbier-Grignard allylation of benzaldehyde in water (Eq. 8.73).172 Recently, a study was completed in which some water-tolerant allylating agents were prepared in situ from allylmagnesium chloride and various metallic salts reacted with aldehydes in THF-FLO to afford the desired homoallylic alcohols.173... 

In reactions of chiral aldehydes, TiIV compounds work well as both activators and chelation control agents, a- or A-oxygcnated chiral aldehydes react with allylsilanes to afford chiral homoallylic alcohols with high selectivity (Scheme 22).85 These chiral alcohols are useful synthetic units for the synthesis of highly functionalized chiral compounds. Cyclic chiral 0,0- and A/O-acetals react with allylsilanes in the same way.86,87 Allenylsilanes have also been reported as allylation agents. 

Ally 1-tin compounds are employed as more reactive allylating agents. Because of their high reactivity, less active catalysts (TX species having mild Lewis acidity) or less reactive substrates are often required (Scheme 23).88,89 In addition to carbonyl compounds as substrates, allylation reactions of imines have been also reported.90 Also, a binuclear TiIV Lewis acid has been developed (compound (C) in Scheme 23), which shows higher catalytic activity than the mononuclear analogue (D) because of bidentate coordination to the carbonyl moiety of the substrate.91... 

Solutions containing allylbarium compounds are highly regio- and stereospecific allylation agents for carbonyl 318 319... 

TABLE 3-12. Some Commonly Used Allylating Agents... 

For convenient reference, some commonly used allylating agents are listed in Table 3-12. 

Radical allylations with allylsilanes 71 occur under mild conditions in good to excellent yields, provided that the radical precursor and the silane have the appropriate electronic pairing [85]. The two examples in Reactions (7.75) and (7.76) show the reactivity matching of the allylating agent with the radical. These reactions offer tin-free alternatives for the transformations that are currently carried out by allyl stannanes. 

A C2-chiral bisformamide (18) derived from diaminocyclohexane catalyses the enantioselective allylation of simple aldimines, using allyltrichlorosilane in the presence of L-proline.44 The more immediate allylating agent is, in fact, L-proline derivative (19), formed in situ, and observed by NMR and MS. 

Dialkylalkoxyborane 29 is treated with ethanolamine to liberate homoallylic alcohol 7 - this work-up allows the recycling of the chiral auxiliary.13 After precipitation of the (IPC)2B-ethanolamine adduct 30 it can be transformed into the allylating agent 27 via compound 31. 

Anisidine imines of aldehydes, p-McOCfJ I4-N=CI IR (R = Ar, alkyl) can be ally-lated with anti-selectivity, using triethylborane and a Pd(II)-phosphine catalytic system, avoiding metallic or metalloid allylating agents 54 The imines can be conveniently formed in situ. 

A regio- and enantio-selective palladium-catalysed allylic alkylation of ketones has been reported, using allyl enol carbonate chemistry in which a CO2 unit tethers the allylating agent to the nucleophile.198... 

Triazole 90 (Scheme 20) is efficiently allylated at N-l under Pd(0) catalysis, affording 1-allyltriazoles 91. No N-4 allylation products were detected (93T1465). Under similar conditions, 1,2,4-triazolethione 92 is allylated at the sulfur atom under kinetic control to give sulfide 93. If excess allylating agent is introduced, the second allylation takes place at N-l or at N-2 to afford compounds 94 and 95 (93T1465). 

The Pd(0)-catalyzed allylations of 120, benzothiazolethione 123, and benz-imidazolethione 125 (Scheme 26) have been studied by the current authors (93T1465). In all cases, the sulfides 121 (R = Ph), 124, and 126 were formed, either as major or as exclusive products. Attempts to isomerize sulfides into A-cinnamyl derivatives were made. Slow conversions were observed for sulfides 121 (R = Ph) and 124 under forcing conditions, thus indicating that sulfides are the products of kinetic control and the /V-cinnamyl derivatives are the products of the thermodynamic control (N > S), which is not easily attainable. Of course, the reaction of 125 with two equivalents of allylating agent gives the S./V-dicinnamyl derivative 127. 

Several methods promoted by a stoichiometric amount of chiral Lewis acid 38 [51] or chiral Lewis bases 39 [52, 53] and 40 [53] have been developed for enantioselective indium-mediated allylation of aldehydes and ketones by the Loh group. A combination of a chiral trimethylsilyl ether derived from norpseu-doephedrine and allyltrimethylsilane is also convenient for synthesis of enan-tiopure homoallylic alcohols from ketones [54,55]. Asymmetric carbonyl addition by chirally modified allylic metal reagents, to which chiral auxiliaries are covalently bonded, is also an efficient method to obtain enantiomerically enriched homoallylic alcohols and various excellent chiral allylating agents have been developed for example, (lS,2S)-pseudoephedrine- and (lF,2F)-cyclohex-ane-1,2-diamine-derived allylsilanes [56], polymer-supported chiral allylboron reagents [57], and a bisoxazoline-modified chiral allylzinc reagent [58]. An al-lyl transfer reaction from a chiral crotyl donor opened a way to highly enantioselective and a-selective crotylation of aldehydes [59-62]. Enzymatic routes to enantioselective allylation of carbonyl compounds have still not appeared. 

Generally, the Lewis acid-promoted allylation of aldehydes with allyltrimethylsilanes proceeds via carbonyl activation. However, the SnCU-promoted allylation with allylsilanes bearing a coordinate site is rationalized by a transmetallation mechanism, in which allyltrichlorostannanes work as the actual allylating agents (Equation... 

The TBAF-catalyzed allylation of aldehydes with 10 proceeds efficiently in refluxing THF.92 In contrast, a Pd-TBAF co-catalyst system enables the allylation at room temperature (Equation (20)).93 This mild allylation is due to the formation of a bis-7r-allylpalladium complex as the actual allylating agent. 

The radical-initiated allylation of alkyl halides with allyltris(trimethylsilyl)silanes proceeds via an SH2 process mediated by a tris(trimethylsilyl)silyl radical.225 The radical-allylating agents react with alkenes, alkynes, and aldehydes via a radical chain process to give the corresponding allylsilylation products.226... 

Allylic compounds with good leaving groups, such as bromide aricl iodide, are excellent allylating agents but they suifer from loss of regiochemistry due to competition between the direct S 2 and... 

It is very well known that jr-allyl palladium complex 1, which is a key intermediate for the Tsuji-Trost type allylation, has an electrophilic character and reacts with nucleophiles to afford the corresponding allylation products. We discovered that bis 7r-allyl palladium complex 2 is nucleophilic and reacts with electophiles such as aldehydes [27] and imines [28-32] (Scheme 2, Structure 2). We have also shown that bis 7r-allyl palladium complex 2 can act as an amphiphilic catalytic allylating agent it reacts with both nucleophilic and electrophilic carbons at once to produce double allylation products [33]. These complexes incorporate two allyl moieties that can bind with different hapticity to palladium (Scheme 3). The different complexes may interconvert by ligand coordination. The complexes 2a, 2b and 2c are called as r]3,r]3-bisallypalladium complex (also called bis-jr-allylpalladium complex), r)l,r)3-bis(allyl)palladium complex, -bis(allyl)palladium complex, respectively. Bis zr-allyl palladium complex 2 can easily be generated by reaction of mono-allylpalladium complex 1 and allylmetal species 3 (Scheme 4) [33-36]. Because of the unique catalytic activities of the bis zr-allyl palladium complex 2, a number of interesting cascade reactions appeared in the literature. The subject of the present chapter is to review some recent synthetic and mechanistic aspects of the interesting palladium catalyzed cascade reactions which in-... 

Asymmetric Allylation of Prochiral Aldehydes. The asymmetric allylation reaction is useful for stereoselective carbon-carbon bond formation, and therefore development of an effective method for the synthesis of optically active homoallyl alcohols was sought. A chiral allylating agent, readily generated from tin(II) trifluoromethanesulfonate, chiral diamine 1, and allyldi-isobutylaluminum, was efficiently employed in the asymmetric allylation of aldehydes in 1996 (eq 16). ... 

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