Allylation and Propargylation of Carbonyl Compounds

Allylation and propargylation of carbonyl compounds have been surveyed [5]. This section focuses on regio- and stereochemical aspects of the carbonyl allylation reactions in organic and aqueous media. Allylation of carbonyl compounds also proceeds under solvent-free conditions [10] or in liquid carbon dioxide [11]. Allylation with a catalytic amount of indium (0.01-0.1 equiv.) in combination with manganese and chlorotrimethylsilane has been reported [12]. Allylindium reagents have successfully been applied to syntheses of several natural products [13]. 

Paquette and co-workers have extensively surveyed the effect of proximal groups on diastereoselectivity in the addition of allylindium to a carbonyl group. When a-and yS-hydroxy aldehydes are subjected to the allylation, excellent diastereocontrol 

Stereoselective 1,4-asymmeric stereoinduction under aqueous conditions is realized by use of oxygen-substituted allylic indium reagents (Tab. 8.5) [30]. O-Silylated allylindium shows moderate anti selectivity, via the FeUdn-Anh transition state, whereas hydroxy-bearing allylindium exhibits syn selectivity by dual coordination of indium intramolecularly to the hydroxy group and intermolecularly to the aldehyde. 

The indium-mediated enantioselective allylation of aldehydes is realized in the presence of external chiral ligands (-I-)-cinchonine and (-)-cinchonidine (Tab. 8.6) [38]. By 

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From InCl3, highly reactive low-valent indium(i) species are electrochemically generated and regenerated. These are used for allylation and propargylation of carbonyl compounds (Scheme 3). Of special interest are bisallylations of aromatic and aliphatic esters, since such conversions cannot be achieved by using conventional stoichiometric allylations of esters by means of indium metal or Ini.66... 

Allylations, allenylations, and propargylations of carbonyl compounds in aqueous media can also be carried out with preformed organic tin reagent, rather than the use of metals.86,87,88 For example, the allylation reaction of a wide variety of carbonyl compounds with tetraal-lyltin was successfully carried out in aqueous media by using scandium trifluoromethanesulfonate (scandium triflate) as a catalyst (Eq. 8.40).89 A phase-transfer catalyst (PTC) was found to help the allylation mediated by tin at room temperature without any other assistance.90... 

The chemistry of asymmetric allylation of carbonyl compounds has further progressed since the review in Comprehensive Asymmetric Catalysis [1] and plenty of papers including reviews [2,3] on chiral catalysts for the reaction have since appeared. This chapter describes new examples of catalytic enantioselec-tive allylation of carbonyl compounds with allylmetals in the presence of a catalytic amount of chiral Lewis acid or chiral Lewis base (Scheme 1). Compounds 1-36 [4-49] shown in Fig. 1 are the chiral catalysts reported since 1998, which have been used in the asymmetric allylation or propargylation of carbonyl compounds. Chiral compounds 37-40 [50-53], which have been utilized in the stoichiometric version, are also candidates for the chiral catalyst (Fig. 2). 

Allylation and Propargylation of Compounds other than Carbonyl... 

As expected according to the HSAB principle, hard electrophiles such as silyl halides and triflates react at the enolate oxygen atom to form allenyl ketene acetals, while soft electrophiles such as carbonyl compounds attack at C2. Only allylic and propargylic halides react regioselectively at G4 of the allenyl enolate to give substituted conjugated dienes. 

Carbonyl Allylation and Propargylation. Boron complex (8), derived from the bis(tosylamide) compound (3), transmeta-lates allylstannanes to form allylboranes (eq 12). The allylboranes can be combined without isolation with aldehydes at —78°C to afford homoallylic alcohols with high enantioselectivity (eq 13). On the basis of a single reported example, reagent control might be expected to overcome substrate control in additions to aldehydes containing an adjacent asymmetric center. The sulfonamide can be recovered by precipitation with diethyl ether during aqueous workup. Ease of preparation and recovery of the chiral controller makes this method one of the more useful available for allylation reactions. 

The chiral rhenium complexes of allylic and propargylic alcohols 841 are selectively oxidized by IBX to the unsaturated carbonyl compounds 842 in good yields (Scheme 3.334) [1139]. 

The addition of a-sulfinyl carbanions to carbonyl compounds followed by further functional group modification has proved to be an efficient and highly stereoselective approach to epoxides, a-aminoketones, a-aminoaldehydes, a-hydroxy esters, and allylic and propargylic alcohols [76-80]. 

Palladium-catalyzed carbonylation of allylic and propargylic compounds offers a potential tool of one-carbon homologation. Particularly, pd-catalyzed carbonylation of propargylic compounds further provides synthetically valuable transformations because of the high reactivity of the intermediary allenyl esters. 

J. Tsuji and J. Kiji, in Transition Metals for Organic Synthesis, Vol. 1, M. Beller and C. Bolm, Eds., Wiley-VCH, Weinheim, 1998, 68-78. Palladium-Catalyzed Carbonylation of Allylic and Propargylic Compounds. 

Benzyl halides and allyl (propargyl) halides are structurally similar but have drastically different chemical reactivities in the aqueous Barbier-Grignard-type reactions. Although tribenzyl and dibenzyltin derivatives have been prepared in aqueous conditions since the 1960s, they do not add onto carbonyls, most likely because it is not possible to form a six-membered cyclic transition state with the carbonyl group in a two-componenf fashion. Still, zinc-mediated benzylation of carbonyl compounds in aqueous media was reported by Bieber et al. recently. The benzylation of 4-nitrobenzaldehyde could be controlled chemoselectively by using various phase transfer catalysts and metal reductants in water (Eq. 4.41). 2... 

Propargylic lithium alanates or lithium borates react with allylic halides or with carbonyl compounds in a regioselective manner to furnish 1,1 -disubstituted allenes (Scheme The reaction between alkyl halides and aluminum metal is the basis of the oldest method for the synthesis of organoaluminum compounds. For example, propargylic bromides react with aluminum in ether giving organoaluminum compounds that on treatment with acetals yield solely a-allenic ethers (equation 1)." However, the reaction of simple alkyl halides with aluminum metal requires a long reaction time. 

Extension of this reaction to electrophiles other than aldehydes was unsuccessful [22, 23], However, propargylic boronates were found to react with allylic halides and various carbonyl compounds [23], The boronates were prepared by lithiation of a methyl-substituted alkyne with t-butyllithium followed by treatment with a trialkylborane. The propargylic boronate preferentially reacts with the electrophile at the y-position to yield propargylic products (Eq. 9.20). The methodology has also been applied to alanates with comparable results. 

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