Synthesis metal enolates

In spite of their intrinsic synthetic potential, addition reactions of metal enolates of non-stabilized esters, amides, and ketones to epoxides are not widely used in the synthesis of complex molecules. Following the seminal work of Danishefsky [64], who introduced the use of Et2AlCl as an efficient catalyst for the reaction, Taylor obtained valuable spiro lactones through the addition reaction of the lithium eno-late of tert-butyl acetate to spiro-epoxides, upon treatment of the corresponding y-... 

A direct application of the ring-opening reaction of an epoxide by a metal enolate amide for the synthesis of a complex molecule can be found in the synthesis of the trisubstituted cyclopentane core of brefeldin A (Scheme 8.35) [68a]. For this purpose, treatment of epoxy amide 137 with excess KH in THF gave a smooth cyclization to amide 138, which was subsequently converted into the natural product. No base/solvent combination that would effect cyclization of the corresponding aldehyde or ester could be found. 

Reviews on stoichiometric asymmetric syntheses M. M. Midland, Reductions with Chiral Boron Reagents, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 2, Chap. 2, Academic Press, New York, 1983 E. R. Grandbois, S. I. Howard, and J. D. Morrison, Reductions with Chiral Modifications of Lithium Aluminum Hydride, in J. D. Morrison, ed.. Asymmetric Synthesis, Vol. 2, Chap. 3, Academic Press, New York, 1983 Y. Inouye, J. Oda, and N. Baba, Reductions with Chiral Dihydropyridine Reagents, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 2, Chap. 4, Academic Press, New York, 1983 T. Oishi and T. Nakata, Acc. Chem. Res., 17, 338 (1984) G. Solladie, Addition of Chiral Nucleophiles to Aldehydes and Ketones, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 2, Chap. 6, Academic Press, New York, 1983 D. A. Evans, Stereoselective Alkylation Reactions of Chiral Metal Enolates, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 3, Chap. 1, Academic Press, New York, 1984. C. H. Heathcock, The Aldol Addition Reaction, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 3, Chap. 2, Academic Press, New York, 1984 K. A. Lutomski and A. I. Meyers, Asymmetric Synthesis via Chiral Oxazolines, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 3, Chap. 

D. A. Evans in Asymmetric Synthesis, Ed. J. D. Morrison, Academic Press, New York (1984), Vol 3, Chpt 1 (stereoselective alkylation reactions of chiral metal enolates)... 

Asymmetric induction in the aldol reaction of enolsilane and metal enolate nucleophiles with yS-substituted aldehydes gives rise to both excellent yields and good diastereoselectivities (equation 128)507. The best diastereoselectivity was obtained using a trimethylsilyl enolate in the presence of boron trifluoride-etherate (92 8 anti. syn). The key step in the synthesis of the N-terminal amino acid analogue of nikkomycin B and Bx (nucleoside peptide antibiotics) has been performed using this type of methodology508. 

Silyl enolates undergo Pd-catalyzed arylation with aryl halides in the presence of an additive such as Bu3SnF,327 CuF2,328 or ZnF2.329 The arylation of silyl enolates has higher functional group tolerance than that of alkali metal enolates. The ZnF2-promoted arylation is valuable for efficient, stereoselective synthesis of a-arylated esters and imides (Equation (89)). 

Over the past 30 years, the widespread use of Sml2 in organic synthesis has brought the chemistry of Sm(III) enolates to the fore as many processes using the reagent involve the formation and reaction of these organometallic species. Although Sm(III) enolates can be exploited as nucleophiles in a number of reactions, their reactivity is still poorly understood and they appear to behave differently to more conventional metal enolates for example, there are few... 

Charette recently described an innovative activation protocol in which lactams, in the presence of triflic anhydride (33), react with pyridines to afford the pyridinium imidate 107 in good yield. Subsequent addition of metal enolates to this species leads to 2-substituted tricyclic dihydropyridines, advanced intermediates for the total synthesis of the natural alkaloid ( )-tetraponerine T4 (109, Scheme 16) [107]. 

Metal enolates are widely used as building blocks in modem organic synthesis. A thorough understanding of their structure and reactivity is important, particularly since many of these... 

Metal enolates of carbonyl compounds are important nucleophiles in C—C bondforming reactions for the synthesis of nonfluorinated compounds. However, the metal enolates of fluorinated carbonyl compounds have been severely limited to a-F metal enolates, which can be stabilized by chelate structures containing the M—F moiety. In sharp... 

Cleavage of thf by LiR occurs with formation of ethylene and the metal enolate of acetaldehyde (ethenolate), the simplest enolate anion. For example, Li(OCH=CH2) results from the reaction of LiR (R = n-Bu , t-Bu ) with thf and it has been used in the synthesis of other metal enolato complexes. 

Michael addition of metal enolates to a,/3-unsaturated carbonyls has been intensively studied in recent years and provides an established method in organic synthesis for the preparation of a wide range of 1,5-dicarbonyl compounds (128) under neutral and mild conditions . Metal enolates derived from ketones or esters typically act as Michael donors, and a,-unsaturated carbonyls including enoates, enones and unsaturated amides are used as Michael acceptors. However, reaction between a ketone enolate (125) and an a,/3-unsaturated ester (126) to form an ester enolate (127, equation 37) is not the thermodynamically preferred one, because ester enolates are generally more labile than ketone enolates. Thus, this transformation does not proceed well under thermal or catalytic conditions more than equimolar amounts of additives (mainly Lewis acids, such as TiCU) are generally required to enable satisfactory conversion, as shown in Table 8. Various groups have developed synthons as unsaturated ester equivalents (ortho esters , thioesters ) and /3-lithiated enamines as ketone enolate equivalents to afford a conjugate addition with acceptable yields. 

As far as the use of electrochemical oxidation of metal enolates in organic synthesis is concerned, more than 30 years ago the electrochemical oxidation of lithium ester enolates was used for the preparation of snccinate esters . An excellent review on the applications of anodic electrochemistry in organic synthesis has been published . 

Transition metal enolates were introduced into organic synthesis in 1981 by Reetz and Peter, who reported that titanium enolates are easily accessible using cheap reagents, distillable and miscible in THF, ether, methylene chloride or pentane, and display pronounced erithro selectivity in reactions with aldehydes. Since then, the importance of these versatile nucleophiles has steadily increased and compounds which can be represented as 57 or 58 have been identified. 

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