Acyclic and cyclic ketones

A sequence of reactions for conversion of acyclic and cyclic ketones into a,(3-unsaturated ketones with insertion of a =CHCH3 unit has been developed. The method uses l-lithio-l,l-dichloroethane as a key carbenoid reagent. The overall sequence involves three steps, one of them before and one after the carbenoid reaction. By analysis of the bonding changes and application of your knowledge of carbene reactions, devise a reaction sequence that would accomplish the transformation. 

Organic-Base Catalyzed. Asymmetric direct aldol reactions have received considerable attention recently (Eq. 8.98).251 Direct asymmetric catalytic aldol reactions have been successfully performed using aldehydes and unmodified ketones together with chiral cyclic secondary amines as catalysts.252 L-proline and 5,5-dimethylthiazolidinium-4-carboxylate (DMTC) were found to be the most powerful amino acid catalysts for the reaction of both acyclic and cyclic ketones as aldol donors with aromatic and aliphatic aldehydes to afford the corresponding... 

The sequential double migratory insertion of CO into acydic and cydic diorganozircono-cene complexes through acylzirconocene and ketone—zirconocene species provides a convenient procedure for preparing acyclic and cyclic ketones (Scheme 5.6) [8], Thus, the bi-cydic enones from enynes can be obtained through CO insertion into zirconacyclopen-tenes followed by a subsequent rearrangement (Scheme 5.7). The scope and limitations of this procedure have been described in detail elsewhere [8d]. This procedure provides a complementary version of the well-known Pauson Khand reaction [9]. 

The cathodic reduction of ketones ( )-RCHMeC(0)R (R = Ph, R = Ph, Me R = cyclohexyl, R = Me) afforded mixtures of diastereomeric alcohols. The origin of the diastereoselectivity, which depends on R and R and the electrolysis conditions, is discussed [333]. Acyclic and cyclic ketones with a chiral center in the fi-position yielded diastereomers in a ratio different from that obtained by LiAlH4-reduction [334]. 

A straightforward method for aldolizing unsymmetrical ketones on the more hindered side involves the use of catalytic titanium(lV) chloride in toluene at room temperature. For examples using acyclic and cyclic ketones, and linear, branched, and aromatic aldehydes, the regioselectivity varied from 7 1 to >99 1, while the symanti ratios were moderate to good, and yields were in the range 62-91%. In contrast to other methods, base is not required, and the ketone can be used as is (i.e. the silyl enol ether is not required). 

A sequence of reactions for converting acyclic and cyclic ketones a,jS-unsaturated ketones with an additional =CCH3 unit has been developed. 

Acyclic and cyclic ketones may be oxidized to esters or lactones, respectively, by a variety of oxidants including peracids or peroxides associated with suitable catalysts. This reaction is known as Baeyer-Villiger (BV) oxidation and it was originally applied to the oxidation of menthone and tetrahydrocarvone with monopersulfuric acid (equation 69). With the increase of environmental concern, much research has focused on the development of catalytic BV processes based on green and cheap oxidants like hydrogen peroxide and relatively non-toxic metals (Re, Pt, Ti). ... 

Excellent enantioselectivities up to complete asymmetric induction are achieved in the preparation of a-alkylated aldehydes, acyclic and cyclic ketones via (-)-(S)- and (+ )-(7 )-1 -amino-2-methoxymethylpyrrolidine (SAMP/RAMP-hydrazones) (see Section 1.1.1.4.2.). Due to the unique mechanism of metalation and alkylation, the absolute configuration of the final products can be predicted. Since both antipodes of the auxiliary are available, either enantiomer of the desired alkylated carbonyl compound can be prepared... 

Ketone synthesis. Dialkylation of 1 under phase-transfer conditions results in the dimethyl dithioacetal S,S-dioxide derivative of a ketone, which is hydrolyzed to the ketone when heated with hydrochloric acid in methanol. The sequence provides a route to both acyclic and cyclic ketones.3... 

Therefore, based on the known cyclocondensation of arylidenemalonodinitriles and 1-arylethylidenemalonodinitriles in the presence of piperidine to give 1,6-di-cyanoanilines [66a], Wang and coworkers [67] have developed a straightforward microwave irradiation-assisted pseudo-four-component synthesis of the anilines 62. Thus, the reaction of (hetero)aromatic aldehydes 63, acyclic and cyclic ketones 64 and 2 equiv. of malononitrile in the presence of triethylamine or piperidine furnishes, after 2 min of 300 W-irradiation power, 51-63% of 2,6-dicyanoanilines 62 (Scheme 5.12). 

The enolate ions of ketones have become the most widely studied nucleophiles in SrnI reactions [21-23,40,66]. The enolate ions of acyclic and cyclic ketones (from cyclobutanone to cyclooctanone) [21,40] react with aryl and heteroaryl halides to afford the a-arylation products. No... 

The reaction of these lithium enolates with alkyl halides is one of the most important C-C bondforming reactions in chemistry. Alkylation of lithium enolates Works with both acyclic and cyclic ketones as well as with acyclic and cyclic esters (lactones). The general mechanism is shown below, alkylation of an ester enolate alkylation of a ketone enolate... 

The sulfone moiety is a good acidifying group, so (methylsulfanyl)methyl sulfones 410 and 411 can be deprotonated and mono- or dialkylated with sodium hydroxide under PTC conditions or with sodium hydride619-622. The alkylated products can be easily hydrolyzed with hydrochloric acid in refluxing methanol, having been applied to the synthesis of acyclic and cyclic ketones. The acylation of compound 410 derived sodium anion has been performed with esters620. For the lithiation of a-thiosulfones 411622 and 412, n-BuLi, f-BuLi or LDA at —78 °C can be used. 

Enamines of acyclic and cyclic ketones react with 2,2-dimethoxyethyl esters of a,/ -unsaturated acids in the presence of titanium tetrachloride under very mild conditions to give the Michael adduct with high -selectivity. A reactive l,3-dioxolan-2-ylium salt is formed which reacts with the enamine via a chair-like transition state168... 

Mteto esters can be obtained by acylation of enamines of acyclic and cyclic ketones with ethyl chloroformate3. Surprisingly no /J-keto ester was obtained when the reaction was carried out in the presence of triethylamine and an extra mole of enamine or a tertiary aromatic amine must therefore be used to neutralize the acid liberated The intermediate enamino ester can be isolated and reduced by hydride donors225 (Scheme 92). 

The reaction of both acyclic and cyclic ketones with 1,2-ethanedithiol leads to substituted 1,4-dithiins. It is considered that added l,l -(ethane-l,2-diyl)dipyridinium bistribromide (EDPBT) initially catalyses the formation a 1,3-dithiolane with which it then reacts, bringing about a ring expansion to the dithiin (Scheme 48) <9TL1007>. 

Table 1 Relative Rates of Reduction of Dimethyl Ketals of Acyclic and Cyclic Ketones with HAlClj ...

The Schmidt reaction is closely related to the Beckmann reaction (equation 34). Acyclic and cyclic ketones are transformed to amides and lactams by treatment with hydrogen azide. With bridged bi-cyclic ketones, the regioselectivity of the migration is opposite to the direction of the Beckmann reaction. The Schmidt reaction has been applied to asymmetric synthesis starting from optically active a,a-dialkylated -keto esters. High chemical and optical yields have been obtained (equation 35). ... 

Regiospecific Alkylations of Unsymmetric Acyclic and Cyclic Ketones... 

Fortunately, the use of lithiated hydrazones derived from (S)- or ( )-l-amino-2-methoxymethylpyiro-lidine (SAMP or RAMP) as nucleophiles for asymmetric alkylations have provided a solution to the problems described above with metallated acyclic ketimines and aldimines. Lithiated SAMP or RAMP hydrazones of cyclic ketones are also alkylated in high yields. A major advantage of these chiral hydrazones is that their derivatives of aldehydes, acyclic and cyclic ketones all yield mainly ( )cc-. (Z)cN-Iithiated species on deprotonation with LDA in ethereal solvents under kinetic control. The ( )cc-configuration obtains as a result of the minimization of steric interactions in the usual closed transition... 

Malonic acid ) Citric acid Maleic acid Malic acid Bromomalic acid f Dibromomalic acid Acetylenedicarboxylic acid Acyclic and cyclic ketones Phenol, aniline and derivatives Tartaric acid/Acetone Oxalic acid or Glyoxalic acid Ce(III, IV) Zhabotinskii (Original) [Kasperek Bruice (1971)] [Beck Varady Mag Chem Foly 81 (1975) 519] [Stroot Janjic Helv Chim Acta 58 (1976) 116] [Orban Koros J. Phys. Chem. 82 (1978) 1672] [Rastogi et al. Aachen Meeting (1979) 98-107] [Nosticzius Bodiss J. Am. Chem. Soc. 101 (1979) 3177]... 

The Norrish type I reaction of acyclic and cyclic ketones in solution typically results in recombination, decarbonylation and disproportionation (hydrogen abstraction) products.903 For example, irradiation of di-tert-butyl ketone (265) in hexane solution provides nearly exclusively decarbonylation products from both the singlet and triplet states (>90% chemical yield), whereas the carbonyl group-containing products are produced only in traces (Scheme 6.111).922 923... 

Mesyl azide17 is used to transfer the diazo group to acyclic and cyclic ketones (42, 44, and 46) to provide access to corresponding diazo ketones. a-Disubstituted ketone 44 is converted to the diazo ketone 45 via debenzoylation diazo transfer reaction using p-nitrobenzenesufonyl azide in the presence of DBU.18... 

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