Aldehydes Barbier additions

In a similar vein, allylic iodides and, to a lesser extent, bromides undergo Barbier addition to aldehydes in the presence of activated tin powder in THF (Table 29) [45]. The reaction is thought to involve a diallyltin dihalide intermediate. Similar results were obtained when diallyltin dibromide, prepared independently, was used for the addition. 

Table 29. Barbier additions of allyl halides/Sn to aldehydes.

The general scheme for the one-step Barbier addition reaction of alkenyl and benzylic halides with aliphatic or aromatic aldehydes is shown in Eq. (1). 

Tetraglyme (2,5,8,11,14-pentaoxapentadecane) has been used in the hy-droxymethylation of aldehydes via addition of benzyl chloromethyl ether in the presence of Sml2. Addition of tetraglyme suppresses the competitive pinacol formation, presumably by a complex formation with Sml2 as evidenced by a purple color [25]. Tetraglyme has also been used as a cosolvent in an intramolecular Barbier reaction involving an iodoaldehyde and a THF solution of diiodosamar-ium [26]. 

Barbier conditions have been used to carry out a silicon-induced addition of perfluoroalkyl iodides to DMF to give stable hemiaminal intermediates, which give the perfluonnated aldehydes upon heating with sulfuric acid [47 (equation 38)... 

Recently, the iron-promoted Barbier-type addition of alkyl halides to aromatic aldehydes has been reported (Equation (26)).326 According to the proposed mechanism, the initial step is the formation of an alkyl radical, which can be reduced to the corresponding carbanion. This carbanion nucleophile can react, while coordinated to the iron pentacarbonyl complex, with the corresponding aldehyde. This stoichiometric method is limited with respect to substrate scope and yield. The same authors have also developed the Reformatsky-type addition of cr-halosub-stituted carbonitriles to aldehydes and ketones in the presence of iron pentacarbonyl.3... 

Indium trichloride promotes catalytically the addition of alkynylstannanes to aldehydes (Table 25).42 Metallic indium also mediates the same Barbier-type coupling between alkynyl halides and aldehydes or ketones to give secondary or tertiary propargyl alcohols (Table 26). Secondary alcohols can be oxidized in situ according an Oppenauer process.395 Thus, alkynyl ketones have been prepared from aldehydes via an indium-mediated alkynylation reaction followed by an indium-mediated Oppenauer oxidation. They are also obtained via an indium-mediated alkynylation of the relevant acyl chlorides (Table 27).396... 

Dihaloalkanes have also been used in Sml2-mediated Barbier reactions. For example, Sml2 mediates the addition of diiodomethane to a range of aldehydes and ketones (Scheme 5.71).122 In the case of additions to aldehyde 102, high diastereocontrol is observed. 

Although organosamariums can react with esters and lactones, they preferentially undergo addition to aldehydes or ketones. This allows organosamariums bearing an ester functionality to be generated and used in intermolecular Barbier couplings (Scheme 5.74).98,99... 

Intramolecular Sml2-mediated Barbier Reactions Involving Addition to Aldehydes and Ketones... 

Alkylations. The effect of subjoined Lewis acid (e.g., trimethyl borate) on the catalytic ally lation of aldehydes with allylstannanes promoted by a BINOL-Ti complex has been examined. With allenyltributylstannane the products are homopropargyl alcohols.. Allylation in a Sn(II)-mediated Barbier reaction exhibits much lower ee, although jllenylation with (terminally substituted) propargyltributylstannanes shows good results. 4-Trimethylsilylbut-2-ynyl)tributylstannane undergoes destannylative addition to... 

The first enantiospecific total synthesis of (+)-ajmaline [(+)-17] was developed by Cook et al. 161). D-(+)-Tiyptophan methyl ester (126) was converted enantiospecifically, via intermediate 127, to the optically active )-N -benayltetracyclic ketone (-) 107, which was then transformed into the ot,P-unsaturated aldehyde (-)-128. When compound (-)-128 was stirred with 3-bromo-4-hq>tene in die Barbier Grignard process conditions the 1,4-addition products 129a,b... 

The indium-mediated Barbier reaction has certainly become one of the most popular reactions for creating a carbon-carbon bond under aqueous conditions and has led to spectacular developments in recent years. Compared to other metals, indium is resistant to oxidation, hydrolysis, and has a very low first ionization potential (5.79 eV, in contrast to the second one which is quite normal) which confers on it a remarkable reactivity in Barbier-type reactions. In 1991, Li and co-workers reported the first allylation of aldehydes and ketones mediated by indium in water without any additives or special activation [133]. In particular, the use of indium allowed reactions with acid-sensitive compounds [134] or the preparation of complex carbohydrates such as deaminated... 

Addition of allylic halides to ketones or aldehydes in the presence of Zn in aqueous media, analogous to Barbier reaction or in the absence of solvents (see Toda). 

Cooper et al. reported that the cascade reaction of the palladium-catalyzed cyclization and the Barbier-type allylation of the 1,3-diene-aryl iodide 514, the aldehydes 515, and indium gave the heterocycles 516 in good yields (Scheme 154).220b The reaction proceeds through oxidative addition of a C—I bond of 514 to Pd(0) and subsequent insertion of a double bond of 517 to give the jr-allylpalladium intermediate 518. Transmetalation of the jr-allylpalladium 518 with indium leads to the allylindium complex 519, and the following reaction with the aldehydes 515 gives 516. 

As mentioned in Sect. 2.3, Inanaga and co-workers have demonstrated that Barbier-type reactions of organic halides with carbonyl compounds are promoted by addition of HMPA [16]. They reported a mild convenient method for the direct synthesis of lactones from bromo esters and ketones or aldehydes by using a HMPA-promoted Barbier-type reaction with Sml2 (Scheme 13). They also found that the SmI2/THF-HMPA system was highly useful for the generation of... 

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