Ketones keto sulfoxides

Another way of preparing ketones involves alkylationof 3-keto sulfoxides or... 

Other carbanionic groups, such as acetylide ions, and ions derived from a-methylpyridines have also been used as nucleophiles. A particularly useful nucleophile is the methylsulfinyl carbanion (CH3SOCHJ), the conjugate base of DMSO, since the P-keto sulfoxide produced can easily be reduced to a methyl ketone (p. 549). The methylsulfonyl carbanion (CH3SO2CH2 ), the conjugate base of dimethyl sulfone, behaves similarly, and the product can be similarly reduced. Certain carboxylic esters, acyl halides, and DMF acylate 1,3-dithianes (see 10-10. )2008 Qxj(jatjye hydrolysis with NBS or NCS, a-keto aldehydes or a-... 

Mechanistically, this reaction is similar to ketone acylation. The P-keto sulfoxides have several synthetic applications. The sulfoxide substituent can be removed reductively, which leads to methyl ketones. 

The (3-keto sulfoxides can be alkylated via their anions. Inclusion of an alkylation step prior to the reduction provides a route to ketones with longer chains. 

Diethylamine can readily undergo nucleophilic addition with 1,2-allenyl sulfoxides to afford 2-diethylamino-2-enyl sulfoxides 181, which can be easily converted to a-hydroxy ketones 182 or /3-keto sulfoxides 183 [94]. 

In addition to deoxygenation sulfoxides undergo reductive cleavage at the carbon-sulfur bond when heated in tetrahydrofuran with aluminum amalgam. Keto sulfoxides were thus converted to ketones in usually quantitative yields (the keto group remained intact) [141]. 

Phenolannelation. Methyl vinyl ketone (and substituted vinyl ketones) undergo Robinson annelation with the /(-keto sulfoxide (1) to afford the 5,6,7,8-tetrahydro-2-naphthol (2) with loss of hcn/cnesnlfenic acid. Sodium methoxide is used as base, and the reaction proceeds at 0 - 25°. 

The use of a-thiophenyl enones (106 Scheme 12) allows the preparation of phenols such as (107) from cyclic ketones (18).30 The same product can also be obtained by normal Robinson annulation of methyl vinyl ketone (30) and the p-keto sulfoxide (lOS).30 Acceptors other than a, 3-unsaturated carbonyls have been used in both the Michael reaction and the Robinson annulation process. For example, nu-... 

An impressive new route to enantiopure syn- and anti- 1,2-diols involves sequential diastereoselective DIBAL reduction of oxalyl-di(/V-iucthyl-/V-methoxyainide) following conversion to a corresponding intermediate / -keto sulfoxide a route that involved control of both reductions by the chiral sulfoxide auxiliary.253 Comparison of / -hydroxy ketone systems with die y-sulfoxide-/ -keto systems used here showed this to be die first example of such asymmetric induction by a y-sulfoxide substituent. 

Keto-sulfones, which contain a 2-pyridyl ketone moiety, react with alkylidenemalononitriles to afford 2-amino-5-sulfonyl-4-aryl-6-(pyridin-2-yl)-47/-pyran-3-carbonitriles 86 (Equation 47) <1997JOC6575>. Likewise, (3-keto-sulfoxides featuring a 2-pyridyl ketone moiety react with alkylidenemalononitriles to form 2-amino-5-sulfinyl-4-aryl-6-(pyridin-2-yl)-4//-pyran-3-carbonitriles. Additionally, chiral (3-keto-sulfoxides that contain a 2-pyridyl ketone moiety can add to alkylidenemalononitriles with high stereoselectivity <1997JOC6575>. 

Vinyl ketone equivalent cf., 5, 525-526). y-Keto sulfoxides such as 1 can function as equivalents to vinyl ketones. Thus 1 reacts with dimedone in the presence of triethylaraine (1.5equiv.) in refluxing CH3OH to give the Michael adduct 2 in 79% yield. ... 

Deoxygenation of sulfoxides. Tris(phenylseleno)borane is an effective reagent for the reduction of sulfoxides under mild conditions. Although this reagent converts ketones to selenoketals, selective deoxygenation of keto sulfoxides is possible. Deoxygenation of vinyl sulfoxides also proceeds smoothly. 

Keto Sulfoxides. Cyclic p-keto sulfoxides are readily obtained from the magnesium enolate of the ketone and (—)-menthyl (S)-p-toluenesulfinate as a mixture of diastereomers in which the major epimer has the sulfoxide group in the equatorial orientation (eq 14). 

The stereocontrolled reduction of optically pure P-keto sulfoxides (60) with DIBAL-H anti selective, >93 7) or DlBAL-H in the presence of zinc chloride (syn selective, >95 5) provided an entry to enantio-merically pure alcohols after desulfurization (Scheme 9). The stereoselectivity may be rationalized by consideration of transition states analogous to those described for P-hydroxy ketone reduction (31 and 32), cyclic chelation by zinc chloride and external hydride delivery giving the syn isomer, and coordination of the DIBAL-H to the sulfoxide and internal hydride delivery giving the anti product. 

Optically active 3-keto sulfoxides are readily available from esters and methyl p-tolyl sulfoxide. The ketone function can be reduced with metal hydrides (DIBAL and ZnCl2/DIBAL) giving, with very high diastereoselectivity, opposite configurations in the resulting 3-hydroxy sulfoxides (Scheme 58). ... 

More complex products are obtained from cyclizations in which the oxidizable functionality and the alkene are present in the same molecule. y9-Keto esters have been used extensively for Mn(III)-based oxidative cyclizations and react with Mn(OAc)3 at room temperature or slightly above [4, 10, 11, 15], They may be cyclic or acyclic and may be a-unsubstituted or may contain an a-alkyl or chloro substituent. Cycloalkanones are formed if the unsaturated chain is attached to the ketone. y-Lactones are formed from allylic acetoacetates [10, 11]. Less acidic /3-keto amides have recently been used for the formation of lactams or cycloalkanones [37]. Malonic esters have also been widely used and form radicals at 60-80 °C. Cycloalkanes are formed if an unsaturated chain is attached to the a-position. y-Lactones are formed from allylic malonates [10, 11]. yff-Diketones have been used with some success for cyclizations to both alkenes and aromatic rings [10, 11]. Other acidic carbonyl compounds such as fi-keto acids, /3-keto sulfoxides, j8-keto sulfones, and P-nitro ketones have seen limited use [10, 11]. We have recently found that oxidative cyclizations of unsaturated ketones can be carried out in high yield in acetic acid at 80 °C if the ketone selectively enolizes to one side and the product cannot enolize... 

Corey and Chaykovsky described the reduction of carboxylic esters to ketones by way of / -keto sulfoxides. The ester is treated in tetrahydrofuran with a solution of methylsulfinyl carbanions in a mixture of dimethyl sulfoxide and tetrahydrofuran at 0°. This yields a j8-keto sulfoxide which is reduced with aluminum amalgam in 90% aqueous tetrahydrofuran.527 The methylsulfinyl carbanions are formed by the action of sodium hydride on dimethyl sulfoxide under nitrogen at 65-70°. 

Reaction of acylimidazoles with the appropriate carbon nucleophile has also been used for the preparation of a-nitro ketones and /3-keto sulfoxides. 

DIBAL is the reagent of choice (see also Aluminum Hydride) for the reduction of a ,i8-unsaturated ketones to the corresponding aUyUc alcohols (eq 6). A reagent derived from DIBAL and Methylcopper in HMPA alters the regiochemistry such that 1,4-reduction results (eq 7). Reductions of chiral -keto sulfoxides occur with high diastereoselectivity The choice of reduction conditions makes it possible to obtain both epimers at the carbinol carbon (eqs 8 and 9). 

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