Allyl anion synthon

Oompound 1, 2-(hydroxymethyl )a11y1trimethylsilane, represents a conjunctive reagent which can be considered as the equivalent of zwitterion 2, possessing a nucleophilic allyl anion synthon and an electrophilic allyl... 

I.3.3.2.3.2. Reagents Representing y-Hetero-, a,y- and y,y-Bis(hetero)-Substituted Allyl Anion Synthons, Including Homoenolate Reagents... 

Allyl anion synthons A and C, bearing one or two electronegative hetero-substituents in the y-position are widely used for the combination of the homoenolate (or / -enolate) moiety B or D with carbonyl compounds by means of allylmetal reagents 1 or 4, since hydrolysis of the addition products 2 or 5 leads to 4-hydroxy-substituted aldehydes or ketones 3, or carboxylic acids, respectively. At present, 1-hetero-substituted allylmetal reagents of type 1, rather than 4, offer the widest opportunity for the variation of the substitution pattern and for the control of the different levels of stereoselectivity. The resulting aldehydes of type 3 (R1 = H) are easily oxidized to form carboxylic acids 6 (or their derivatives). 

Whereas an allylsilane can serve as an allyl anion synthon, the reaction of 1,3-bis(silyl)propene with electrophiles can afford the 1,3-disubstituted propene. Thus, treatment of a mixture of (If)- and (Z)-2-aryl-l,3-bis(trimethylsilyl)propenes 5 with 2 equivalents of NBS at —78 °C stereoselectively yields the corresponding (Z)-2-aryl-l,3-dibromopropene 6. When 1 equivalent of NBS is employed, the monobromo product 7 is obtained (equation 5). The reactions apparently proceed via the pattern of sequential displacement of allylsilane moieties40,41. 

Using the tforementioned cyclization of 1-amindiexatrienes, cf. (68) to (70) and (79) to (80), several aromatic compounds have been synthesized upon elimination of a dialkylamine from a dihydroaromatic precursor formed by the 6e electrocyclization process. As an example, dihydrophenanthrene (175) can be synthesized in two different ways depending on the choice of the allyl anion synthon (171 or 173) or... 

Introduction. The title aUylsilane reagent has been enployed as a conjunctive reagent which is considered to be a synthetic equivalent of a zwitterionic, bifunctional compound possessing a nucleophilic allylic anion synthon and an electrophilic cation synthon in the same molecule (1). 

Benzylic anions, ArCHj, are of little importance in the construction of carbon skeletons, and allylic anions, R C—CR—CR", are discussed in the d -synthons section below. 

Table 5. Synthons and Reagents for Carbonyl Addition to x-lIetero-Substituted Allyl Anions...

The carbonyl adducts of allyl phosphine oxides, e. g., 24 and 29 can also be used to make allyl alcohols32 by the reductive removal of the Ph2PO group with lithium aluminium hydride a reaction involving transposition of the double bond, e. g., 24 36. In this approach, the allyl anion of 23 is a reagent for the vinyl anion synthon 37. 

An example, developed by our group, has been presented 3-chloro-propenyl pivalate, the new synthon we propose as a formal a-hydroxy allyl anion, and chromium(II) chemistry allow to achieve the formal diastereo- and enantio-selective a-hydroxyallylation of carbonyl compounds by applying a catalytic cycle based on an in situ produced Salen-chromium complex (Table 8.3). 

Allyl anions (38a),(38b) and (38c) exhibit a similar regioselectivity toward electrophiles, and thus serve as homoenolate synthons. Addition of titanium tetraisopropoxide to (39) followed by condensation with aldehydes gives the anti adducts exclusively, which can be converted to the (Z)-1,3-dienes upon treatment with methyl iodide (Scheme 18). The ( -1,3-dienes can be prepared from the lithiated allyldiphenylphosphine oxide. The stabilized allylic phosphonate anion (40) condenses with carbonyl... 

The selenium group can be removed under very mild oxidative conditions (Scheme 44). Treatment of the anion of (65) with TMS-Cl gives another reagent that can be deprotonated and used with various electrophiles to prepare vinyl silyl ketones (Scheme 45). Therefore, (65) can be used as synthons of (6) and (66), like the 1,3-di(methylthio)allyl anions. ... 

The protected version (61) of (59) can be made from acetoacetate and allylic halide (62) which can come from (58) (cf. Chapters 16 and 35) using acetylene for the vinyl anion synthon. 

Ketones. The reagent (1) is a propenoyl anion synthon. After alkylation, enones are released. On the other hand, the adducts undergo allylic displacement with Grignard reagents, and on hydrolytic workup, ketones are formed. The possibility of creating a-bromoalkyl ketones, 1,4-diketones, 2-ethoxy-2-cyclopentenones, and a-keto enamines bespeaks for the versatility of this synthesis. 

During their study of P(RNCH2CH2)3N-catalyzed 1,2-addition reactions of activated allylic synthons with aldehydes, Verkade et al. found that the reaction of allylic nitrile with aromatic aldehydes alfords the MBH product (195) as the only product in the presence of P(i-PrNCH2CH2)3N 196 (Scheme 2.101). Unlike the nucleophilic pathway proposed for traditional MBH reactions, the reaction is proposed to proceed through the addition of an allylic anion to the aldehyde, affording an intermediate alkoxide anion that undergoes a facile 1,3-proton shift. 

Directed coupling reactions, where no cross-coupling may occur, requires the reagents derived from the appropriate synthons to be ionically different at the reactive site. The carbon-carbon coupling reaction to form hept-l-ene (Expt 5.8), illustrates the importance of selecting the reactive, and readily available, allyl bromide (cationic site) with butylmagnesium bromide (anionic site) (A), rather than the other alternative (B). 

In the palladium-catalyzed allylic amination reaction, primary and secondary amines can be used as nucleophiles, whereas ammonia does not react. Therefore, many ammonia synthons have been developed, and a variety of protected primary allyl amines can now be prepared using azide, sulphonamide, phthalimide, di-f-butyl iminocarbonate ((Boc)2NLi), and dialkyl A-(rerr-butoxycarbonyl)phosphoramide anions as the nucleophile [20], An example of the use of ((Boc)2NLi) 30 as the amine nucleophile in the palladium-catalyzed allylic amination reaction is shown in Eq. (9). This reaction also illustrates the problem with the regioselectivity in the reaction as a mixture of the products 31-33 are obtained [21]. 

The anion of 2-(methoxyethoxymethoxy)cyclopropyl phenyl sulfone (methoxyetho-xymethoxy = MEM) is a d -synthon for a,)8-unsaturated aldehydes ". The anion is readily formed by treating 2-(MEM)cyclopropyl phenyl sulfone (359) with n-butyllithium in THE at — 78°C. Treatment of the anion 360 with aliphatic primary bromides or allyl bromide produces the alkylated sulfone 361 in very good yields. Hydrolysis of the MEM-protecting group was readily performed by treatment with aqueous tetrafluoroboric acid to furnish the cyclopropanol sulfone (362). Treatment with aqueous sodium bicarbonate produced the corresponding aldehydes 363 in 70-90 % yields. 

The synthon of the a-acrylate anion is available from a secondary a-keto carboxamide by the Shapiro reaction. The secondary a-ketoamide trisylhydrazones ate ptepar in a one-pot synthesis by reaction of the isocyanides with acid chloride, water and trisylhydrazine in sequence. In DME solvent, the hydra-zone (103) is smoothly metallated with BuLi to give Ae trianion (KH). Allylation of the trianion (104) gives the hydrazone (105). Alternatively, warming (104) up to room temperature yields the dianion (106) which can be intercepted with several electrophiles (Scheme 23). The adduct (107) is readily transformed into the rran -iodo lactone (108) stereospecifically (equation 56). This chemistry also has been applied to a new synthesis of -lactams (Scheme 24). ... 

PhS stabilise carbanions, these allyl compounds 12,13, and 15 form anions which can be used in synthesis. This article describes further developments in our work with these two groups, involving both migration and transposition, leading to regiospecific reagents for synthons with normal reactivity or umpolung and their application to natural product synthesis. 

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