Homoallylation, aromatic aldehydes

The complex 8, formed by the addition of 2-propenylmagnesium chloride to 7, adds to aromatic aldehydes, 1-alkanals, a-branched and unbranched alkanals uniformly from the 7 c-face leading to hoinoallylic alcohols with 88-94% ee35 (Method A). After hydrolytic workup, both components can be recycled. Allyl complexes 10, generated from 9, prefer 67-attack and lead to the ent-homoallylic alcohols with excellent enantioselectivity36 (Method B) (Table 8). 

Si. rra(pentafluorophenyl)boron was found to be an efficient, air-stable, and water-tolerant Lewis-acid catalyst for the allylation reaction of allylsilanes with aldehydes.167 Sc(OTf)3-catalyzed allylations of hydrates of a-keto aldehydes, glyoxylates and activated aromatic aldehydes with allyltrimethylsilane in H2O-CH3CN were examined. a-Keto and a-ester homoallylic alcohols and aromatic homoallylic alcohols were obtained in good to excellent yields.168 Allylation reactions of carbonyl compounds such as aldehydes and reactive ketones using allyltrimethoxysilane in aqueous media proceeded smoothly in the presence of 5 mol% of a CdF2-terpyridine complex (Eq. 8.71).169... 

Table 5 summarizes the reactions of isoprene with aromatic aldehydes and unsaturated aldehydes. Salicylaldehyde provides the expected product as a cyclic boric ester derivative and shows apparently lower stereoselectivity, giving a mixture of 1,3-anti and 1,3-syn isomers in a ratio of 6 1 (run 1, Table 5). 2-Furfural reacts as usual and provides a 1,3-anti isomer as a single diastereomer in good yield (run 2). Unsaturated aldehydes, irrespective of their substitution patterns, undergo homoallylation selectively with excellent 1,3-anti selectivity, the geometry of the double bond of the starting aldehydes remaining intact (runs 3-5). 1,2-Addition to unsaturated aldehyde takes place selectively and no 1,4-addition is observed.

Et2Zn also participates in the reductive coupling as a formal hydride source. Results for the Ni-catalyzed, Et2Zn-promoted homoallylation of carbonyl compounds with isoprene are summarized in Table 7 [30]. Et2Zn is so reactive that for the reaction with reactive aromatic aldehydes it causes direct ethylation of aldehydes, and the yields of homoallylation are diminished (runs 1 and 2). Unsaturated aldehydes seem to be subject to the Michael addition of Et2Zn. Accordingly, for the reaction with cinnamaldehyde, none of the expected homoallylation product is produced instead, the 1,4-addition product of Et2Zn, 3-phenylpentanal is produced exclusively (run 3). 

Homoallyl mercaptans react with aromatic aldehydes in an InC -mediated Prins cyclisation to give substituted tetrahydrothiopyrans 85 with good diastereoselectivity (Scheme 57) <00TL1321>. 

In 2001, the preparation of allylytterbium bromide and the synthesis of homoallylic alcohols using allylytterbium bromide were reported.39 393 Ytterbium metal was found to be activated by a catalytic amount of Mel at 0 °C in THF to produce allylytterbium bromide 66 (Equation (11)). The allylation reaction of a wide range of aromatic aldehydes and ketones proceeded at ambient temperature or less in good to high yields (Table 2). Imines also reacted with allylytterbium bromide to afford homoallyl amines (Table 3). 

The coupling reaction of aromatic aldehydes with their corresponding homoallylic alcohols in the presence of BiCl3 gave symmetric 2,6-disubstituted-... 

Ene reaction of aldehydes. Aliphatic and aromatic aldehydes are not reactive enophiles however, in the presence of dimethylaluminum chloride, which serves as u mild Lewis acid catalyst and proton scavenger, ene reactions occur in reasonable to high yield. Use of C2HSA1C1 results in complex mixtures of products. This ene reaction is a useful route to homoallylic alcohols.2... 

In a gallium-mediated allyl transfer process, bulky gallium homoallylic alkoxides have been retro-allylated to generate (Z)- and ( )-crotylgallium reagents stereo- (g) specifically.195 Immediate reaction with aromatic aldehydes gives erythro- and threo-homoallylic alcohols. 

In 1996, Yamamoto and Yanagisawa reported the allylation reaction of aldehydes with allytributyltin in the presence of a chiral silver catalyst.2 They found that the combination of silver and a phosphine ligand accelerates the allylation reaction between aldehydes and allyltributyltin. After this discovery, they screened several chiral phosphine ligands and found that chiral silver-diphosphine catalysts can effect the reaction in an enantioselective fashion (Table 9.1).2 For example, when benz-aldehyde and allyltributyltin were mixed in the presence of 5 mol% of AgOTf and (S)-2,2 -bis(diphenylphosphino)-1,1 -binaphthyl (BINAP), the corresponding homoallyl alcohol was obtained with 96% ee and 88% yield (Table 9.1). Generally, the reaction with aromatic aldehydes afforded the corresponding homoallyl alcohols in excellent... 

Reaction of RCHO with CJfCH=CHCH1Cl. This reaction can be regio-selective and f/ireo-selective when mediated by Sn and Al. The reaction of benz-aldehyde with cinnamyl chloride provides the anfi-homoallylic alcohol as the only detectable product. This diastereoselectivity obtains generally with aliphatic or aromatic aldehydes. The reaction with enals under the same conditions provides only the 1,2-adducts, again with anti-selectivity (equation I). The reaction of 2-phenylpropanal with 1 provides a mixture of homoallylic alcohols in the ratio 3 1, with anti-selectivity at the C—C bond formed in the reaction (equation II). 

Asymmetric allylation is performed by chiral allylating reagents. The chiral allyltin generated in situ from benzodio-stannole [Sn(02C6H4)], allyl halide, chiral dialkyl tartrates and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) reacts with aromatic aldehydes in the presence of copper salts to afford the chiral homoallyl alcohols (Equation (50)).164... 

The reaction of 1,3-dibromopropene with carbonyl compounds mediated by indium in water gives 3,3-disubsti-tuted propene 63 (Scheme 55). In the formation of 63, 1,3-dibromopropene acts as a w-allyl dianion synthon. Aromatic aldehydes generally have a higher selectivity than aliphatic ones in the product formation. Unsubstituted and electron-withdrawing group-substituted benzaldehydes give mainly 3,3-disubstituted propene 63. For electron-rich benzaldehydes, the formation of both 3,3- 63 and 1,3-disubstituted propene 64 is dramatically decreased and the selectivity is reversed completely to give diene 65 and homoallylic alcohol 66.219... 

Evidence for a closed transition-state model was gathered on the basis of the diastereoselectivity in reactions of pentacoordinate allylic silicates. Bis(l,2-benzenediolato)allylsilicates la and lb, which can be prepared via the reactions of E- and Z-crotyltrichlorosilanes with dilithium catecholate, react with aromatic aldehydes to give the corresponding homoallylic alcohols 2 in high yields3 (Scheme 3.2a). Unlike allyltrimethylsilane,4 the allylation reactions of... 

They also applied this method to the intermolecular ene reactions of aliphatic and aromatic aldehydes with alkenes containing a disubstituted vinylic carbon, a potentially valuable route to homoallylic alcohols [50]. Proton-initiated rearrangements do not take place, because the alcohol-Lewis acid complex formed in the ene reaction reacts readily to give methane and a non-acidic aluminum alkoxide. Formaldehyde and excess Me2AlCl gave good yield of ene adducts with all types of alkene, as exemplified in Sch. 26. 

Three-component reactions of aldehydes, amines, and allyltributyltin also proceeded smoothly in micellar systems with Sc(OTf)3 as Lewis acid catalyst, to afford the corresponding homoallylic amines in high yields (Eq. 19) [68]. Not only aromatic aldehydes but also aliphatic, unsaturated, and heterocyclic aldehydes worked well. The procedure is very simple—merely mixing an aldehyde, an amine, and allyltributyltin in the presence of Sc(OTf)3 and SDS in water no homoallylic alcohol (an adduct between an aldehyde and allyltributyltin) was produced. It was suggested that imine formation from aldehydes and amines was very fast under these conditions, and that the selective activation of imines rather than aldehydes was achieved. 

A chiral reagent derived from tin(II) catecholate, DBU, allyl bromide, and (+)-di-/-butyl tartrate reacts with aromatic aldehydes in a Cul-catalyzed reaction, giving homoallylic alcohols sometimes in excellent optical purities. Allylation with allyltrichlorosilane has been conducted in the presence of 45 and 46 (cf. allenylation of aliphatic aldehydes ). Allylsilanes modified by a tartrate ester show a range of effectiveness in chirality transfer. ... 

The generation and subsequent reaction of oxy-functionalized allylic zirconium reagents to a wide range of aldehydes proceeds with excellent anti selectivity [188]. Allylic zirconium reagents can also be prepared from the hydrozirconation of allenes [189]. Very high levels of diastereoselectivity for both simple aliphatic and aromatic aldehydes are observed in these reactions for the production of the anti homoallylic alcohol (Scheme 10-97). 

Second, if tin(II) catecholate is ligated by an optically active dialkyl tartrate, it will react with an allylic bromide or iodide and an aldehyde, in the presence of Cul as catalyst, to give the optically active homoallylic alcohol. The enantioselectivity is highest when the alkyl groups of the tartrate are bulky (t-butyl or cyclohexyl). Aromatic aldehydes give higher enantioselectivities than do aliphatic aldehydes, and the reaction is also successful with a-carbonylketones 74... 

Several other metals have been used in this Barbier-type reaction. Thus, a mixture of bismuth(III) chloride/aluminum [160] or of bismuth(III)chloride/ magnesium [161] was shown to promote allylation of aldehydes under aqueous conditions yielding homoallylic alcohols in good yields. Similarly, the same reaction can be promoted with metallic lead [162], highly reactive antimony prepared by the NaBH4 reduction of SbClj [163] or a mixture of manganese and catalytic copper [164]. In the latter case, aromatic aldehydes reacted whereas ali-... 

Iseki et al. later improved the catalytic process and showed that chiral phos-phoramides 15,16, and 17, prepared from (S)-proHne, are suitable to catalyze the asymmetric allylation of aromatic aldehydes to give chiral homoallylic alcohols 34 with up to 88% ee (Scheme 13) [36,37]. The same group has also developed a chiral formamide 18 as a chiral Lewis base catalyst [38]. This catalyst is convenient for the allylation of aUphatic aldehydes with high enantioselectivity. A typical aromatic aldehyde, benzaldehyde, gives a low enantiomeric excess (Scheme 13). 

The reaction of aldehydes with another titanium complex generated from E-crotyl iV-diisopropyl carbamate, s-BuLi, sparteine 2.5 and Ti(0 -Pr)4 gives anti homoallylic alcohols with a good enantioselectivity [109, 1162, 1163] (Figure 6.29). Addition of allylaluminum reagents to aromatic aldehydes in the presence of Sn(OTf>2 and a chiral amine also gives useful results [842],... 

The reactions of aldehydes with y-alkoxystannanes 2.81 are catalyzed by BF3 Et20, and they are more selective toward syn E-homoallyl alcohols 6.62 than the previous examples [1214, 1217] (Figure 6.56). This holds for the reactions with prochiral or a-chiral aldehydes provided that the reagents are matched [569], Transition-state model Aj accounts for this selectivity. This method has been applied by Yamamoto and coworkers [1223] to the reaction of aromatic aldehydes with y-(tetrahydropyranyk>xy)-allylstannanes under AICI3 catalysis. 

Allylation of aldehydes. The reagent, prepared by reaction of diallyldimethyl-silane with triflic acid, reacts with aromatic aldehydes at low temperatures to afford homoallylic alcohols. 

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