By Enolates

Titanium Complexes of Unsaturated Alcohols. TetraaHyl titanate can be prepared by reaction of TYZOR TPT with aHyl alcohol, followed by removal of the by-product isopropyl alcohol. EbuUioscopic molecular weight determinations support its being the dimeric product, octaaHoxydititanium. A vinyloxy titanate derivative can be formed by reaction of TYZOR TPT with vinyl alcohol formed by enolization of acetaldehyde (11) ... 

It has been reported that exchange of protons activated by enolization can be performed directly in a glass inlet system of the mass spectrometer prior to analysis by heating the sample at about 200° with deuterium oxide vapor for a few minutes. " Exchange has been observed with 2-, 3-, 6-, 11- and 17-keto steroids, but the resulting isotopic purity is usually poor,... 

During the course of base-catalyzed exchange in O-deuterated alcohols, the vinylic hydrogen in the a position to the ketone is replaced by deuterium, in addition to the hydrogens activated by enolization. Thus, under these conditions the exchange of androst-l-en-3-one (16, R = H) gives a trideuterio derivative (18) instead of the expected 4,4-d2 analog (16, R = D). " (For other examples see compounds 13, 19, 21, 23, 26 and 27.) Incorporation of this deuterium is due to rapidly reversible alcohol addition (16 -+17) and elimination (17 18) which competes with the enolization step. " ... 

Treatment of dibromocarbene adduct (43) (Rji, = O) with aqueous methanol containing silver nitrate or perchlorate gives A-homo-estra-1 (10), 2,4a-triene-4,17-dione (45) in 21 % overall yield from the enol ether (42). The exact pathway is not known, but the first step may be formation of a bromo-homo-dienone facilitated by the methoxyl group, which then undergoes further loss of hydrogen bromide involving shift of a double bond by enolization. ... 

Coumarin formation proceeds via an intramolecular attack by enol ester 9 on the ketone to give 10. Dehydration of 10 then affords coumarin 11. It has been observed that coumarins are favored when higher order homologs of acetic anhydride and their corresponding salts such as propionic anhydride/sodium propionate and butyric anhydride/ sodium butyrate are used. 

The enolic form of 2 was confirmed by a ferric chloride color reaction and by its acidity and ultraviolet spectrum, A-Aroyl derivatives of amino acids other than glycine fail to form such azlactones, probably because the stabilization afforded by enolization cannot occur. 

Propiolactone is subject to attack by enolate ions to give propionic acid derivatives of ketones. It may likewise react with nucleophilic enamines to give carboxyethylation according to the reactions. The morpholide is easily hydrolyzed to the corresponding acid. 

Nitroalkenes are shown to be effective Michael acceptor B units In three sequential re fA + B + C couplingi in one reaction vessel. The sequence is initialed by enolate nucleophiles fA and is terminated by aldehydes or acrylate electrophiles fC. The utility of this protocol is for rapid assembly of complex stnictures from simple and readily available components. A short total synthesis of a pyrroLmdine alkaloid is presented in Scheme 10.16. ... 

At the stage of the ketone 20, or the analogous methyl carboxylate, further substituents can be introduced diastereoselectively by Grignard additions or by enolate methodology4 6. 

The reduction rate of R (low reduction potential)1 is faster than any chemical reaction such as trapping by enolate ion. The difference from the electrochemical results is that, in the latter, the secondary reduction of the sulfinate anion does not occur. 

Ferrocen-l,l -diylbismetallacycles are conceptually attractive for the development of bimetal-catalyzed processes for one particular reason the distance between the reactive centers in a coordinated electrophile and a coordinated nucleophile is self-adjustable for specific tasks, because the activation energy for Cp ligand rotation is very low. In 2008, Peters and Jautze reported the application of the bis-palladacycle complex 56a to the enantioselective conjugate addition of a-cyanoacetates to enones (Fig. 31) [74—76] based on the idea that a soft bimetallic complex capable of simultaneously activating both Michael donor and acceptor would not only lead to superior catalytic activity, but also to an enhanced level of stereocontrol due to a highly organized transition state [77]. An a-cyanoacetate should be activated by enolization promoted by coordination of the nitrile moiety to one Pd(II)-center, while the enone should be activated as an electrophile by coordination of the olefinic double bond to the carbophilic Lewis acid [78],... 

Osmium tetroxide used in combination with sodium periodate can also effect alkene cleavage.191 Successful oxidative cleavage of double bonds using ruthenium tetroxide and sodium periodate has also been reported.192 In these procedures the osmium or ruthenium can be used in substoichiometric amounts because the periodate reoxidizes the metal to the tetroxide state. Entries 1 to 4 in Scheme 12.18 are examples of these procedures. Entries 5 and 6 show reactions carried out in the course of multistep syntheses. The reaction in Entry 5 followed a 5-exo radical cyclization and served to excise an extraneous carbon. The reaction in Entry 6 followed introduction of the allyl group by enolate alkylation. The aldehyde group in the product was used to introduce an amino group by reductive alkylation (see Section 5.3.1.2). 

Reaction sequence E removed an extraneous oxygen by Sml2 reduction and installed an oxygen at C(15) by enolate oxidation. The C(l) and C(15) hydroxy groups were protected as a carbonate in Step E-5. After oxidation of the terminal vinyl group, the C-ring was constructed by a Dieckmann cyclization in Step F-4. After temporary protection of the C(7) hydroxy as the MOP derivative, the (1-ketoestcr was subjected to nucleophilic decarboxylation by phenylthiolate and reprotected as the BOM ether (Steps F-5, F- 6, and F-7). 

The mechanism of [3 + 2] reductive cycloadditions clearly is more complex than other aldehyde/alkyne couplings since additional bonds are formed in the process. The catalytic reductive [3 + 2] cycloaddition process likely proceeds via the intermediacy of metallacycle 29, followed by enolate protonation to afford vinyl nickel species 30, alkenyl addition to the aldehyde to afford nickel alkoxide 31, and reduction of the Ni(II) alkoxide 31 back to the catalytically active Ni(0) species by Et3B (Scheme 23). In an intramolecular case, metallacycle 29 was isolated, fully characterized, and illustrated to undergo [3 + 2] reductive cycloaddition upon exposure to methanol [45]. Related pathways have recently been described involving cobalt-catalyzed reductive cyclo additions of enones and allenes [46], suggesting that this novel mechanism may be general for a variety of metals and substrate combinations. 

Enol lactones can also be obtained from keto acids by enolization-dehydration. Adlumidiceine (103) as well as N-methylhydrasteine (104) when heated in toluene with acetic anhydride or p-toluenosulfonic acid were transformed to enol lactones 97 (97) and 98 (5,102), respectively. Narceine (106) under the influence of PC13 yielded 101 (87,100). 

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