Acyl anions lithium

Advances in the use of anionic stereogenic phosphorus have been interesting. Acylation of lithium o-anisylphenylphosphide with chloro-formates bearing chiral alkyl groups provided a diastereomeric mixture that could be induced to undergo an inversion at phosphorus (at relatively low temperature) to form the more favorable diastereoisomer in a crystalline lattice.186 Subsequent conversion to the quaternary phos-phonium species was followed by removal of the acyl group and isolation of the chiral tertiary phosphine as the borane derivative (Equation 3.10). 

An example where the presence of a counterion makes a difference between the gas phase and solution phase pathways involves the intriguing carbanion produced on deprotonation of 1,3-dithiane at C-2. In solution, this species, almost invariably produced by reaction of the dithiane with butyllithium, is widely used as an acyl anion equivalent in synthetic chemistry. Its importance for the present work is that this is a configurationally stable lithiated species in solution the carbanion stays sp -hybridized, and the lithium prefers the equatorial position, even to the extent of driving a terr-butyl group on the same acidic C-2 carbanion to the axial position in the lithiocarbon species. The carbanion is thought to be stabilized primarily by orbital overlap with the C-S antibonding orbitals, as opposed to more conventional polar and 7t-resonance stabilization. ... 

The first of these are called carbene complexes and the latter are referred to as carbyne complexes.61 The first carbene complex was reported in 1964 by Fischer and Maasbol62 and was prepared by reaction of hexacarbonyltungsten with methyl or phenyl lithium to generate an acyl anion which was then alkylated with diazomethane. 

Likewise 1,3-dithianes can be deprotonated by alkyl lithium bases and the resulting anions are strong nucleophiles. The ditliiane group can be hydrolyzed back to the carbonyl group. Thus the dithiane serves as a synthon for the acyl anion. 

Acyl anions (RC(=0)M) are unstable, and quickly dimerize at temperatures >-100 °C (Section 5.4.7). These intermediates are best generated by reaction of organolithium compounds or cuprates with carbon monoxide at -110 °C and should be trapped immediately by an electrophile [344—347]. Metalated formic acid esters (R0C(=0)M) have been generated as intermediates by treatment of alcoholates with carbon monoxide, and can either be protonated to yield formic acid esters, or left to rearrange to carboxylates (R0C(=0)M —> RC02M) (Scheme 5.38) [348]. Related intermediates are presumably also formed by treatment of alcohols with formamide acetals (Scheme 5.38) [349]. More stable than acyl lithium compounds are acyl silanes or transition metal acyl complexes, which can also be used to perform nucleophilic acylations [350],... 

Cyanide (one carbon) and acetylene (two carbons) are limited and other acyl anion equivalents are more versatile. Dithians are thioacetals of aldehydes that can be deprotonated between the two sulfur atoms by strong bases such as BuLi. Reaction with a second aldehyde gives 27 and hydrolysis of the thioacetal by acid, usually catalysed by Cu(II) or Hg(II), gives the a-hydroxyketone 4. The disconnection is that shown on diagram 4 and the lithium derivative 26 acts as the acyl anion 2. Unlike previous methods, R1 does not have to be H or Me. 

An alternative was used by Baldwin in the work that led to his famous rules for cyclisation.8 He needed to study the cyclisation of the hydroxy-enone 36 and an obvious aldol disconnection led back to the a-hydroxy-ketone 37. The same disconnection requires the addition of an acyl anion equivalent 39 to cyclohexanone and Baldwin chose the lithium derivative 40 of a vinyl ether. 

You might also have considered the addition of an acyl anion equivalent, such as the lithium derivative of the dithian 74 to ArCHO (chapter 23). There are obviously many other methods but these are the most likely. 

In the next section the formation of acyl anion equivalents by nucleophilic addition to thiocarbonyl compounds is discussed. A direct and non-classical route to thiocarbonyl anions has been achieved [141]. Treatment of a thiocarbamoyl chloride by lithium powder, in the presence of both naphthalene and the carbonyl compound to which the intermediate will be added, led to a-hydroxy thioamides. 

The lithiation of an O-vinyl carbamate with rAr-BuLi followed by transmetallation with zinc bromide provides the convenient acyl anion derivative, which undergoes smooth Pd(0)-catalyzed cross-coupling reactions (Equation (24)).67 This reaction sequence has been extended to lithium enolates. The deprotonation of the aminoester with LDA followed by a transmetallation with zinc bromide in ether furnishes a zinc enolate, which readily adds to the double... 

Lithiated enol carbamates 559 have been reported as complementary acyl anion equivalents of MVL (524) and EVL (525). Non-fluorinated enol carbamates have been prepared by O-carbamoylation of acetaldehyde lithium enolate (80-87% yield) or by quantitative addition of trimethylsilylamides to vinyl chloroformate837. 

Acylate anions can be made by nucleophilic attacks of lithium alkyls on metal carbonyls, for example, W(CO)6 + LiR - Li[(C0)5WC(0)R]. They are precursors of alkylidenes which will be discussed shortly. 

Addition of an acyl anion or its equivalmt to a,p-unsaturated ketones is an important synthetic mediod for 1,4-dicaibonyl compounds. In the palladium method for 1,4-dicartxHiyl compounds, a vinyl Grignard or vinyllithium reagent is used as a synthetic equivalent of the acetyl anion. Reaction of lithium divinylcuprate with 2-cyclohexenone (44) afforded 3-vinylcyclohexanone (45). which was oxidized to the 1,4-diketone (46 Scheme 12). ° ... 

The most systematically investigated acyl anion equivalents have been the IMS ethers of aromatic and heteroaromatic aldehyde cyanohydrins, TBDMS-protected cyanohydrins, - benzoyl-protected cyanohydrins, alkoxycaibonyl-protected cyanohydrins, THP-protected cyanohydrins, ethoxyethyl-protect cyanohydrins, a-(dialkylamino)nitriles, cyanophosphates, diethyl l-(trimethylsiloxy)-phenyimethyl phosphonate and dithioacetals. Deprotonation di these masked acyl anions under the action of strong basie, usually LDA, followed by treatment with a wide varies of electrophiles is of great synthetic value. If the electrophUe is another aldehyde, a-hydroxy ketones or benzoins are formed. More recently, the acyl caibanion equivalents formed by electroreduction of oxazolium salts were found to be useful for the formation of ketones, aldehydes or a-hydroxy ketones (Scheme 4). a-Methoxyvinyl-lithium also can act as an acyl anion equivalent and can be used for the formation of a-hydroxy ketones, a-diketones, ketones, y-diketones and silyl ketones. - - ... 

The addition of lithium and Grignard reagents to isocyanides which do not contain a-hydrogens proceeds by an a-addition to produce a metalloaldimine (7, an acyl anion equivalent). The lithium aldimines are versatile reagents which can be used as precursors for the preparation of aldehydes, ketones, a-hy-droxy ketones, a-keto acids, a- and 3-hydroxy acids, silyl ketones and a-amino acids (Scheme 5). - ... 

The lithium salts of aldehyde t-butylhydiazones react with electrophiles (aldehydes, ketones, alkyl halides) to form C-trapped t-butylazo compounds isomerization and hydrolysis give a-hydroxy ketones or ketones in good yields, thereby providing a convenient path via a new acyl anion equivalent (Scheme 6). Reaction of th lithium salts with aldehydes and ketones, followed by elimination, provides a new route to azaalkenes, whereas homolytic decomposition of C-tnq>ped azo compounds of trityl and diphe-nyl-4-pyridylmethylhydrazones lead to the formation of alkanes, alkenes, alcohols or saturated esters. ... 

Trimethylsiloxy cyanohydrins (9) derived from an a,3-unsaturatied aldehyde form ambident anions (9a) on deprotonation. The latter can react with electrophiles at the a-position as an acyl anion equivalent (at -78 C) or at the -y-position as a homoenolate equivalent (at 0 C). The lithium salt of (9) reacts exclusively at the a-position with aldehydes and ketones. The initial kinetic product (10) formed at -78 C undergoes an intramolecular 1,4-silyl rearrangement at higher temperature to give (11). Thus the initial kinetic product is trapped and only products resulting from a-attack are observed (see Scheme 11). The a-hydroxyenones (12), -y-lactones (13) and a-trimethylsiloxyenones (11) formed are useful precursors to cyclopentenones and the overall reaction sequence constitutes a three-carbon annelation procedure. 

Acyl Anions Derived from Lithium Acetylide... 

Lithium aldimine (131), an acyl anion equivalent derived from an isocyanide and an organolithium reagent, adds to aldehydes giving, after quenching with water, a-amino ketones (134) via the Amadori rearrangement (Scheme 33)." The a-amino ketone (134) results from a double tautomerization of a-hydroxy imine (132), formed initially after quenching with water. Thus, the imine (132) isomerizes to enolamine (133), which in turn tautomerizes to the observed product (134). 

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