Ynolate

Carboxylic esters can be converted to their homologs (RCOOEt RCH2-COOEt) by treatment with Br2CHLi followed by BuLi at —90°C. The ynolate RC=COLi is an intermediate.If the ynolate is treated with 1,3-cyclohexadiene, followed by NaBH4, the product is the alcohol RCH2CH2OH. ... 

ETHYL 1 -NAPHTHYLACETATE ESTER HOMOLOGATION VIA YNOLATE ANIONS... 

Rajarathnam E. Reddy and Conrad J. Kowalski 146 ETHYL 1 -NAPHTHYLACETATE ESTER HOMOLOGATION VIA YNOLATE ANIONS... 

Lithium ester enolate addition to imines has been used for the construction of optically active p-lactams, e.g. 64 and the lithium enolates have been found to be superior to other metal derivatives for both yields and diastereoselectivity in some cases <00H(53)1479>. Immobilized lithium ester enolates have been utilized for the first time <00OL907> and soluble polymer supported imines were used to obtain N-unsubstituted azetidin-2-ones under mild conditions <00CEJ193>. Both lithium and titanium enolates have been employed to obtain cholesterol absorption inhibitors <99TA4841>. Lithium ynolates 65 add to imines to provide P-lactams in good to excellent yield <00TL5943>. 

An efficient preparation of hexahydro-isoxazolo[2,3- ]pyridin-2-ones relies on the anionic addition of nucleophiles at the electrophilic carbon of the nitrone followed by cyclization of the resulting Ar-oxide. As shown by results collected in Scheme 31, various nucleophiles can be engaged in the reaction and include enolates 95 <20020L3119> or 98 <2000BML1811>, silyl acetals 101 <2003TL2817>, or ynolates 103 <20020L3119> (Scheme 31). 

A naphthalene-catalyzed (<10%) lithiation of a,a-dibromo esters 152 in THF at —78°C was used to generate ester dianions 153, which by warming at 0°C gave lithium ynolates 154. These intermediates were trapped by carbonyl compounds, for instance benzophenone, to give, after final hydrolysis with water, a,/3-unsaturated acids 155 (Scheme 55)" ... 

Lithium phenylethynolate (520) has been prepared in a rather intriguing fashion through the elimination of benzonitrile from 5-lithio-3,4-diphenylisoxazole (519) (75AG(E)765). Reaction of the ynolate with an aldehyde or ketone was shown to afford a metallated /3-lactone (521). Treatment of this intermediate in turn with an electrophilic reagent such as benzyl bromide produced a tri- or tetra-substituted /3-lactone (522 Scheme 114). 

The cycloaddition of the /V-2-methoxvphenvI aldimines with lithium ynolates (for a review see [134]) has been reported to give (3-lactams enolates, that... 

R1 = Me, Bu R2 = Ph,Naph OMP = o-OCH3-Ph single or mixture of diastereomers Scheme 50 Cycloaddition of ynolates with A -2-mcthoxyphcnyl imines affording P-lactams... 

A highly Z-selective olefination of a-oxy and a-amino ketones via ynolate anions has been reported (Scheme 9).43 The stereocontrol mechanism has been explained by (g) orbital interactions between the s orbital of the breaking C-O bond or n orbital of the enolate and the s orbital of the C-O or C-N bonds of the substituent in the ring opening of the /I-lactone enolate intermediates, and/or the chelation to lithium. 

Tetrasubstituted alkenes (214) were obtained with high Z selectivity (>99 1) by reaction of ynolates (211) with a-oxy- and a-amino-ketones (212 X = OR, NR2) (g) at room temperature. According to experimental and theoretical studies, the high Z selectivity is induced by orbital interactions in the ring opening of the /3-lactone enolate intermediate (213), rather than by the initially presumed chelation of the lithium atom.260... 

In a new benzannulation procedure, the 4 + 2-cycloaddition of lithium ynolates (131) with (trialkylsilyl)vinylketenes (132) yields, via an intermediate 3-(oxido)dienyl-ketene (133), the highly substituted phenols (134), which can be converted to ben-zofurans and benzopyrans (Scheme 37).135 The reaction of buta-2,3-dienoate with vinylketenimine yields the expected Diels-Alder adduct together with an unexpected aniline formed by a competing 2 + 2-cycloaddition.136 The first example of a... 

Ynolate anions react with acylsilanes at low temperature to give P-lactones 48 in good yields. When the reaction is conducted at room temperature the isolated product is a (1-silyl-a,p-unsaturated ester via a P-lactone enolate intermediate <02JACS6840>. 

From the diacetate ester (Figure 7.13), an ion-molecule complex consisting of the neutral ketene and the complementary alcoholate is formed. Either this complex dissociates to yield the ethylene glycol acetate anion A, which further fragments to yield the acetate anion E, or a proton transfer from the ketene to the alcoholate occurs in the complex, which after dissociation yields the ynolate ion G. 

When the 3-position of the isoxazole is blocked, but the 5-position free, ring opening is again either concurrent with deprotonation or takes place under very mild conditions. In these substrates fission of both the N—O bond and the C3—C4 bond occurs, giving a nitrile and an ynolate ion (49). The latter is usually hydrolyzed on work-up to a carboxylic acid, R CH2C02H,1 but can be trapped at low temperatures. As exemplified by Scheme 7, such reactions could provide useful syntheses of ketenes and /Mactones.159... 

A synthetic method for the preparation of multisubstituted furans employing ynolates has been described <20070L1963>, which can also be used for the preparation of pyrroles and thiophenes. 

One of the best methods to synthesize cyclopentenone derivatives is the Pauson-Khand procedure. However, Shindo s group have recently developed a domino process consisting of a [2+2] cycloaddition of a ketone with an ynolate, followed by a Dieckmann condensation to give a (3-lactone as 4-190 which is decarboxylated under reflux in toluene in the presence of silica gel to afford cyclopentenones [64a]. Thus, the reaction of 4-188 and 4-189 led to 4-190, which on heating furnished the linear cucumin 4-191 (Scheme 4.41). This natural product has been isolated from the mycelial cultures of the agaric Macrocystidia cucumis [65, 66]. The domino procedure described was also used to synthesize dihydrojasmone and a-cuparenone. Moreover, the [2+2] cycloaddition can be combined with a Michael reaction [64b]. 

A review on ynolates, including the synthesis of p-lactones, has appeared <03S2275>. Morita-Baylis-Hillman-type adducts have been converted into a-alkylidene-p-lactones 65, which on reaction with dimethyltitanocene can be transformed into 3-alkylidene-2-methyleneoxetanes <03OL399>. Lactones 66 have been obtained via the cinchona alkaloid-catalyzed dimerization of monosubstituted ketenes <03OL4745>. The PdCh-promoted synthesis of P-lactones 67 have been achieved via cyclocarbonylation of 2-alkynols <03OL4429>. 

Chiral nitrone 99 reacted with ynolates such as 100 at low temperature to give 5-isoxazolidinones with good diastereoselectivity. The 4,4-dimethyl-5-isoxazolidinone 103 could be obtained in high yield and with good diastereoselectivity by treating the initially generated enolate 101 with Mel <03S1441>. 

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