Allenylation of aldehydes

A chiral bis-oxazoline catalyses asymmetric Nozaki-Hiyama allenylation of aldehydes.179 For example, benzaldehyde is converted to silylated allene (62) using a bromoalkynylsilane, BrCH2-C = C-SiR R2 the product is readily desilylated quantitatively without loss of ee. 

Diethylzinc catalyses allenylation of aldehydes and ketones by an allenyl boronate, via a site-selective B/Zn exchange a balance of allenyl and propargyl alcohols are produced. A mild enantioselective addition of vinylzinc reagents (derived from vinyl iodides and diethylzinc) has been reported, with wide tolerance of functional groups. 

Boaretto, A. Marton, D. Tagliavini, G. (1985a) Allylstannation. VI. Allylation and allenylation of aldehydes and ketones by allyl- and allenyl-tin chlorides in the presence of water, J. Organomet. Chem., 286,9-16. 

Arylative or silylative cyclizations of allenyl aldehydes or ketones have been reported (Equations (101) and (102)).459,459a The intermolecular process, that is, three-component coupling reaction of aldehydes, allenes, and arylboronic acids, is catalyzed by palladium as well (Equation (103)).46O 46Oa These reactions are proposed to proceed through nucleophilic attack of the allylpalladium intermediates to the carbonyl groups. 

Closely related to both allyl carbenoids and the allenyl carbenoids discussed above, propargyl carbenoids 101 are readily generated in situ and insert into zirconacycles to afford species 102 (Scheme 3.27), which are closely related to species 84 derived from allenyl carbenoids [65], Protonation affords a mixture of allene and alkyne products, but the Lewis acid assisted addition of aldehydes is regioselective and affords the homopropargylic alcohol products 103 in high yield. Bicydic zirconacyclopentenes react similarly, but there is little diastereocontrol from the ring junction to the newly formed stereocenters. The r 3-propargyl complexes derived from saturated zirconacycles are inert towards aldehyde addition. 

The nucleophilic attack on an acceptor-substituted allene can also take place at the acceptor itself, especially in the case of carbonyl groups of aldehydes, ketones or esters. Allenic esters are reduced to the corresponding primary alcohols by means of diisobutylaluminum hydride [18] and the synthesis of a vinylallene (allenene) by Peterson olefination of an allenyl ketone has also been reported [172]. The nucleophilic attack of allenylboranes 189 on butadienals 188 was investigated intensively by Wang and co-workers (Scheme 7.31) [184, 203, 248, 249]. The stereochemistry of the obtained secondary alcohol 190 depends on the substitution pattern. Fortunately, the synthesis of the desired Z-configured hepta-l,2,4-trien-6-ynes 191 is possible both by syn-elimination with the help of potassium hydride and by anti-elimination induced by sulfuric acid. Analogous allylboranes instead of the allenes 189 can be reacted also with the aldehydes 188 [250]. 

Propargylic ethers undergo directed lithiation and subsequent transmetallation to afford oxygenated allenyl titanium reagents. Subsequent addition of aldehydes gives rise to various homopropargylic alcohol adducts as mixtures favoring the anti dia-stereomers (Tables 9.18 and 9.19) [29, 30]... 

The oxidation of allenylsulfonamides 75 is also possible by using DMDO [23], Unlike the corresponding reaction of allenyl acids, oxidation of allenyl sulfonamides usually cannot be stopped after the formation of the allene oxide 76 but proceeds further to the spirodiepoxide intermediate 77, finally giving hydroxypyrrolidinone 78 and hydroxypiperidone 79, respectively (Scheme 17.23). Similarly to y-allenyl alcohols, aldehydes and acids, five-membered heterocycles, e.g. 80, are also formed from y-allenylsulfonamides. In the latter case the reaction can be terminated after the first epoxidation by addition of p-toluenesulfonic acid. 

When, instead of aldehydes, A-tosyl imine 196 is used as an electrophile in a reaction with lithiated methoxyallene 183, allenyl imines 197 result. As shown in Scheme 26, they can be converted into pyrrole derivatives 198 and 199"" . 

Reactions of allenylzinc bromide reagents with aldehydes afford increased amounts of propargyl adducts compared to analogous additions to ketones (Table 3). Presumably, diminished steric interactions render the aldehyde propargylic adducts more stable than their ketone counterparts. Alternatively, equilibration of the kinetic propargylic adducts with the allenyl isomers is slower for the adducts of aldehydes. 

Brown and co-workers developed a novel homoallenyl boronate reagent 169 based on diisopropyl tartrate for the stereoselective homoallenylation of aldehydes 170. The reagent 169 was prepared via homologation of the corresponding allenyl boronate or the alkylation of halomethyl boronate with allenyl Grignard similar to those reported in Scheme 26. The allyl boronate 169 upon reaction with aldehydes furnished the dienyl alcohols 172 with high ee (Scheme 28) <1996JOC100>. 

Many noticeable examples of chiral Lewis base catalyzed allylation of carbonyl compounds have also appeared. Iseki and coworkers published a full paper on enantioselective addition of allyl- and crotyltrichlorosilanes to aliphatic aldehydes catalyzed by a chiral formamide 28 in the presence of HMPA as an additive [41]. This method was further applied to asymmetric allenylation of aliphatic aldehydes with propargyltrichlorosilane [40]. Nakajima and Hashi-moto have demonstrated the effectiveness of (S)-3,3 -dimethyl-2,2 -biquinoline N,AT-dioxide (29) as a chiral Lewis base catalyst for the allylation of aldehydes [42]. In the reaction of (fs)-enriched crotyltrichlorosilane (54 , E Z=97 3) with benzaldehyde (48), y-allylated anfi-homoallylic alcohol 55 was obtained exclusively with high ee while the corresponding syn-adduct was formed from its Z isomer 54Z (fs Z= 1 99) (Scheme 6). Catalytic amounts of chiral urea 30 also promote the asymmetric reaction in the presence of a silver(I) salt, although the enantioselectivity is low [43]. 

Allyltriorganosilanes react with activated C-N double bonds such as iminium salts and Lewis acid-coordinated imines at the y-position to give homoallylamines.14,118 For example, in the presence of BF3, iV-acylimines generated in situ by the reaction of aldehydes or acetals with carbamates are efficiently allylated with allyltrimethylsilanes (Equation (26)).119,119a,12° The use of homochiral crotylsilanes such as 20 leads to highly diastereo- and enantioselective synthesis of homoallylamines (Equation (27)). a Allenylation of the iV-acylimines can be performed with propargylsi lanes. 

Substituted prop-2-ynyl mesylates cause propargylation of aldehydes with Snl2, BU4NI, and Nal in DMI to furnish 2-substituted but-3-yn-l-ols, while 3-substituted prop-2-ynyl mesylates promote allenylation under the same conditions to produce 2-substituted buta-2,3-dien-l-ols (Equation (57)). 

The indium-mediated cyclization of acetylenic aldehyde 59 affords the corresponding ethenylidenecyclohexanol derivative 60 in 44% yield (Equation (37)).217 A similar intramolecular allenylation of 61 prompted by indium in aqueous THF produces chromane 62 in good yield (Equation (38)). 

Propargylic halides are converted to allenyl and propargylic tin halides upon exposure to SnCl2 in a mixture of A(,A(-dimethylformamide (DMF) and l,3-dimethyl-2-imidazo-lidinone (DMI) [87]. Subsequent addition of aldehydes leads to homopropargylic and/or allenic carbinols (Table 47). The ratio of the two regioisomeric adducts depends on the nature of and R. Alkyl substitution on the alkyne (R = Me) strongly favors the allenic adduct. On the other hand, the ratio of adducts from the TMS substituted alkyne (R = TMS) is dependent on the aldehyde substituent. 

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 reactions of allenyl- and propargylsilanes with functionalized aldehydes bearing chiral residues have also been studied. Grde and coworkers observed high diastereoselectivity in the reaction of aldehyde 6.71 bearing a butadieneiron carbo-... 

The mechanism of the condensation between allenyl organometallics and carbonyl groups is thought to be a cyclic Se< (or 5e2 ) process. In the reaction of aldehydes with 1,2-butadienylmagnesium halides, the anti syn product ratio depends on the size of substitutent group of the aldehyde and may be rationalized as shown in (1). ... 

Related Sc(OTf)3-catalyzed allylation of aldehydes with allyl-tributyltin in nitromethane, allylation of aldehydes with allyl-germanes, allylation of acylsilanes, and intramolecular allenylation of propargyl silanes have also been reported. The allylation of aldehydes with tetraallyltin proceeds smoothly in micellar systems without using any organic solvents. Novel allylation of aldehydes with alkeneylepoxides is catalyzed by Sc(OTf)3 to produce 5-hydroxy-a, 8-unsaturated aldehydes. ... 

Insertion Reactions. Trimethylsilyldiazomethane undergoes net insertion between the B-C bond of borinate and boronate esters. Thus, olefin hydroboration, followed by treatment with TMSCHN2, oxidation, and desilylation offers a method for hydroxymethylation of alkenes in fair to moderate yield (eq 54). Stable, chiral allenylboranes (IR and IS) are prepared by reaction of TMSCHN2 with 5-MeO-9-BBN followed by resolution with pseudoephedrine and reaction with allenyl magnesium bromide (eq 55). Compounds IR and IS are useful for the asymmetric allenylboration of aldehydes with predictable absolute stereochemistry. The precursors to 1 are then readily recovered during work-up. ... 

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