Dianion derivative

The dianions derived from furan- and thiophene-carboxylic acids by deprotonation with LDA have been reacted with various electrophiles (Scheme 64). The oxygen dianions reacted efficiently with aldehydes and ketones but not so efficiently with alkyl halides or epoxides. The sulfur dianions reacted with allyl bromide, a reaction which failed in the case of the dianions derived from furancarboxylic acids, and are therefore judged to be the softer nucleophiles (81JCS(Pl)1125,80TL505l). 

There is a marked and unexplained difference in the stability of the dianions derived by deprotonation of coumarilic acid (207) and 4,6-dimethylcoumarilic acid (209) to thermal... 

Dianions derived from cychc ct-nitro ketones have been used for the preparadon of the natiirM product phoracanthhde and related raacrocychc lactones fsee Scheme 5 2 Alkyladon of dianion of ct-nitro cydic ketones is followed by radicM denitradon v/ith Bn-vSnHfsee Secdon... 

Addition of the dianion derived from tetrahydro-2-(2-nitroethoxy)-2//-pyran (8) to (5)-2-methylbutanal provides two of the four possible diastereomeric products in 64% yield. The major component, probably the (2/ ,3/ ,4.5)-diastereomer, is formed in 73% diastereoselectivity1S. 

Thus, the dianion derived from a-amino acid substitutes the /1-chloride to give the ester of 2-(phenylsulfonyl)ethenyl amino acid and subsequent desulfonylation provides N-(benzoyl)vinylalanine methyl ester (62) (equation 61). The conjugate addition of enolates to methyl styryl sulfone (63) and subsequent intramolecular addition to the carbonyl moiety provide a synthetically valuable method for the construction of bicyclic and tricyclic skeletons52. Desulfonylation of the cyclization product 64 with sodium in ethanol-THF gives the diene 65 in good yield (equation 62). 

In some cases, the Grignard reaction can be performed intramolecularly. For example, treatment of 5-bromo-2-pentanone with magnesium and a small amount of mercuric chloride in THE produced 1-methyl-1-cyclobutanol in 60% yield. Other four- and five-membered ring compounds were also prepared by this procedure. Similar closing of five- and six-membered rings was achieved by treatment of a 6- or s-halocarbonyl compound, not with a metal, but with a dianion derived from nickel... 

The dianion derived from methyl 3-nitropropanoate is formed on treatment with LDA, and it is alkylated by alkyl halides exclusively at the 2-position (Eq. 5.6). Elimination of HN02 with DBU in THF furnishes methyl a-methylenealkanoate (see Section 7.3, which discusses alkene formation).12... 

Dianions derived from cyclic a-nitro ketones have been used for the preparation of the natural product phoracanthlide and related macrocyclic lactones (see Scheme 5.2).13 Alkylation of dianion of a-nitro cyclic ketones is followed by radical denitration with Bu3SnH (see Section... 

Scheme 65 summarizes Mori s synthesis of 44 [97]. Reduction of keto ester A with baker s yeast gave hydroxy ester B of about 98% ee. Methylation of the dianion derived from B diastereoselectively gave C, which was converted to 44. This process enabled the preparation of about 10 g of (lS,5R)-44. 

Three tactical approaches were surveyed in the evolution of our program. As outlined in Scheme 2.7, initially the aldol reaction (Path A) was performed direcdy between aldehyde 63 and the dianion derived from tricarbonyl 58. In this way, it was indeed possible to generate the Z-lithium enolate of 58 as shown in Scheme 2.7 which underwent successful aldol condensation. However, the resultant C7 P-hydroxyl functionality tended to cyclize to the C3 carbonyl group, thereby affording a rather unmanageable mixture of hydroxy ketone 59a and lactol 59b products. Lac-tol formation could be reversed following treatment of the crude aldol product under the conditions shown (Scheme 2.7) however, under these conditions an inseparable 4 1 mixture of diastereomeric products, 60 (a or b) 61 (a or b) [30], was obtained. This avenue was further impeded when it became apparent that neither the acetate nor TES groups were compatible with the remainder of the synthesis. 

Two types of electrogenerated carbon bases have commonly been used (1) dianions derived from activated alkenes, and (2) carbanions formed by reductive cleavage of halogen compounds or by direct reduction of weak carbon acids. In both cases, the efficiency of the proton transfer reaction relies on a thermodynamically favored proton transfer or a fast follow-up reaction of the deproto-nated substrate. 

Finally, it should be mentioned that the reaction of the dianion derived from alkynol HC=CC(OH)f-Bu2 with [Fe(CO)4(NMe3)] led to a complex mixture of mono- and polynuclear products, from which the iron(0)-allenylidene complex 42 (Fig. 7) could be isolated [55]. 

Cyclo-coupling between arylalkenes and an aliphatic ester function is achieved by electrolysis in tetrahydrofuran using cathode and anode both of magnesium in an undivided cell. The first electron addition is to the arylalkene. The bond forming steps involves nucleophilic attack by radical-anions or dianions derived from the alkene. Magnesium ions generated at the anode are essential to the process. The... 

The reactivity of oxiranes with lithium enoiates and related compounds has been widely explored and reviewed . Dianions derived from carboxylic acids react readily with oxiranes, but the reaction can be slowed by steric hindrance . The reaction of oxiranes with dianions of acetoacetates is greatly accelerated by the addition of BF3 Et20 " . Oxiranes react readily with lithium salts derived from nitriles , malonates and analogues , lithiated oxazolines and lithio enamines . 

The synthesis of RR)-1% involves in the final (1 + 1) cyclization step (see Scheme 4) a rare example of an inversion of configuration at both chiral centers in the (SiS)-ditosylate precursor during its successive alkylations of the dianion derived from catechol. The (5/ ,15/J)-5,15-dimethylbenzo-15-crown-5 derivative (/ R)-78 is believed (123) to be optically pure. 

Recently the tetrazole moiety has attracted interest as a useful directing group for the lithiation of 5-aryl substituents, with the dianion derivative 62 being obtained in the case of the unsubstituted parent compound and the monolithio species 63 in the case of the 2-trityl derivative (91TL6857 91USP50398I4). With both systems, good yields of products were obtained after reaction with a variety of electrophiles. 

The opportunity for chelation in the various enolate intermediates offers a possible explanation for the observed diastereoselectivities. In the dianions derived from l-acyl-2-pyrrolidinemethanols strong chelation of both of the lithium cations should lead to a rigid enolate structure 9. It is reasonable to assume that the pyrrolidine ring is locked in one conformation. Since, according to models, it is difficult to attribute the observed high diastereoselectivity to steric hindrance, it is probable that the lone pair on the nitrogen directs the facial selectivity of electrophilic attack (see Section 1.1.1.3.3.1.) to one side of the enolate a-carbon. 

Carbonyldiimidazole can also function as a carbonyl equivalent (79TL4517). Condensation of the dianion derived from an a-hydroxy ketone (545) with this reagent provides a general although modest yield approach to tetronic acids (546 equation 7). 

Carbonation of the dianion derived from benzoylacetone occurs at the methyl rather than the methylene group (58JA6360). Sodamide was shown to be the reagent of choice for generation of the dianion. Cyclization of the resulting dioxopentanoic acid by polyphosphoric acid gives 4-hydroxy-6-phenylpyran-2-one. This route has been utilized in the synthesis of a number of naturally occurring 4-hydroxypyran-2-ones acetic anhydride at room temperature is the preferred cyclization medium and the initial formation of a mixed anhydride... 

Aromatic esters may be used to aroylate the dianions derived from 1,3-diketones by reaction with potassium amide (60JOC538). Not only are acetyl and benzoyl acetones suitable for reaction, but alicyclic diketones and 2-hydroxyacetophenone are also acceptable. Cycliz-ation of the triketones occurs in cold sulfuric acid, presumably via the enolic form and the hemiacetal (Scheme 132). 

The synthesis of homophthalic acids has been achieved by carboxylation of the dianion derived from o-methylbenzoic acids (82JCS(Pl)llll). Acetylation is hindered by substitution at the 5-position of the isochroman-l,3-dione and yields of the isocoumarins are reduced in these cases. Deuteration at C-4 can be achieved by deuterating the 4-carboxylic acid, followed by decarboxylation. 

The dianion derived from but-2-ynoic acid reacts with aldehydes to give 5-hydroxyalk-2-ynoates (539). Partial reduction over a Lindlar catalyst and acid-catalyzed cyclization of the resulting enoate gives the dihydropyran-2-one (78LA337). The route is exemplified by the synthesis of the naturally occurring massoia lactone (Scheme 200). In previous work (46JCS954) the hydroxyalkynoic acids themselves, obtained from epoxides and acetylene, were used. 

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