Grignard reagents allylic, reaction with aldehydes

A general procedure for the preparation of keto-aldehydes (8) from cycloalkanones and their conversion into pyridines (9) has been reported. 4 Vinylogous silyl esters (6) are readily prepared from cycloalkanones and these, by reaction with allylic Grignard reagents, followed by hydrolysis, yield alkenes of type (7). The latter compounds are converted into the keto-aldehydes (8) by Pd / -catalysed oxygenation. 

Allyltin compounds can be prepared by simple modifications of the usual reaction involving allyl Grignard reagents (139), by the 1,4-addition of trialkyltin hydrides to 1,3-dienes 140,141), or by the reaction of an aldehyde or ketone with the appropriate, tin-carrying, Wittig reagents (142). 

The reaction of allylic Grignard reagents with aldehydes to produce allylic carbinols does not always proceed smoothly. In the reaction of 3,4-methylene dioxybenzaldehyde with allyl alcohol (1.5-3.0 moles) at ambient temperature... 

The reactions of 2-propenyltitanium reagents with chiral aldehydes (0) or ketones ( and ) usually exhibit enhanced induced diastereoselectivities compared to allyl Grignard reagents. This enhanced diastereoselection is mainly attributed to the greater bulk and lower reactivity of the reagent. Some examples are collected ( )52. 

One of the important new directions in the study of addition reactions of organozinc compounds to aldehydes is the use of ionic liquids. Usually, application of these compounds in reactions with common organometallic reagents has a serious problem ionic solvents are usually reactive toward them, particularly Grignard and organolithium derivatives. It has been recently reported that carbonyl compounds react with allylzinc bromide formed in situ from allyl bromide and zinc in the ionic liquid 3-butyl-l-methylimidazolium tetrafluoroborate, [bmim][BF4].285 Another important finding is that the more reactive ZnEt2 alkylates aldehydes in a number of ionic liquids at room temperature.286 The best yields (up to 96%) were obtained in A-butylpyridinium tetrafluoroborate, [bpy][BF4] (Scheme 107). 

Since an excess of n-BuLi has been inevitable, iron-ate complexes were proposed as catalytic relevant species, which generate a vinyllithium intermediate by carbometallation. The latter was verified by a quench with aldehydes and ketones with generation of the corresponding allylic alcohol. It is important to note that these reactions took place in low yields with alkyl-Grignard reagents. 

These reagents can be obtained by reaction of vinyl Grignard reagents with allylic zinc bromides in THF at - 35 to 0°. Reaction of 1 with ClSn(CH3)3 provides an a-trimethyltin-zinc reagent (2) that is oxidized by air to an aldehyde or ketone (3). ... 

Introduction. Ti-TADDOLates are a,a,a, a -tetraaryl-2,2-disubstituted l,3-dioxolane-4,5-dimethanolatotitanium derivatives. The most common substituents are R, R = Me/Me and Ph/Me, Ar=Ph and 2-naphthyl, X, Y = C1/C1, t-PrO/Cl, Cp/Cl, and i-PrO/i-PtO. The corresponding TADDOLs (2) are available in both enantiomeric forms from tartrate esters which are acetalized (R R CO) and allowed to react with aryl Grignard reagents. The reactions performed in the presence of Ti-TADDOLates or with Ti-TADDOLate derivatives include nucleophilic additions to aldehydes - - and nitroalkenes of alkyl, aryl, and allylic - groups aldol additions hydrophosphonylations and cyanohydrin reactions of aldehydes inter- and intramolecular Diels-Alder additions ... 

Six-centre transition states for the reactions of a carbonyl compound with a Grignard reagent arc very efficient if they allow the formation of a Mg-O bond in concert with the shifts of two pairs of rr or or electrons. Five examples arc shown in Scheine 1.9 (a)-(e). Concerted reduction iind enolization are mentioned above. The allylic addition. Scheme 1.9 (b), is efficient because of the absence of steric hindrance. The carbonyl carbon of an aldehyde may attack ortho to the side chain in benzylmagnesium chloride forming a reactive dihydrobenzene compound, which may-add a second molecule of aldehyde. Scheme 1.9... 

The chiral allyltitanium reagents prepared from the reaction of allyl Grignard or lithium reagents with chiral titanium complexes have been used stoichiomet-rically for the allylic addition to aldehydes with excellent enantioselectivities [71] (Scheme 14.16). Various applications of this methodology in the synthesis of natural products have been reviewed in several articles [72]. 

Miscellaneous Reactions. AICI3 has been used to catalyze the addition of allylsilanes to aldehydes and acid chlorides (eq 37). Cyclic ethers (pyrans and oxepins) have been prepared with hy-droxyalkenes (eq 38). The course of reactions between aldehydes and allylic Grignard reagents can be completely diverted to a-allylation by AICI3 (eq 39). The normal course of the reaction gives y-allylation products. 

Electrophiles also react at C-5 of 1,3-dioxin-4-ones. Two ways of activation have been reported (1) magnesiation of 5-iodo-l,3-dioxin-4-ones afforded the Grignard reagents which can be cross-coupled with allyl halides in the presence of copper cyanide <2001TL6847> or with iodoalkenes under Pd(0) catalysis <2002T4787> and (2) Sc(OTf)3-catalyzed reaction of a side-chain-hydroxylated l,3-dioxin-4-one with aldehydes provided the bicyclic dioxinone in 60-85% yield (Scheme 27) <20050L1113>. 

---