Sulfoxides, p-keto

Solladie G., Carreno M. C. Optically Active P-Keto Sulfoxides and Analogs in Asymmetric Synthesis in Organosulfur Chem. 1995 1, Ed. Page P., Pb. Academic, London... 

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-... 

The mild character of the reaction conditions is exemplified effectively here by the preparation of 2-acetyl-2-cyclohexen-l-one from 2-acetyIcyclohexanone. The crude product is initially isolated entirely in the less stable enedione form which is partially converted to the more stable enol form, 2-ace tyl-1,3-cyclohexadien-l-ol, during distillation at 45-55°. A series of a,(3-unsaturated j3-keto esters, -diketones, and a p-keto sulfoxide have also been prepared in the unenolized form by this... 

Overall yield from /3-keto ester, -diketone, or p-keto sulfoxide. The scale was 0.01-0.005 mole. 

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. 

Pentitol synthesis An asymmetric synthesis of L-arabinitol involves condensation of the (E)-a,fJ-unsaturated ester (2) with the anion of methyl (R)-p-tolyl sulfoxide (1). The resulting p-keto sulfoxide (3) is reduced stereoselectively by ZnCl2/DIBAH (13, 115-116) to 4. Osmylation of 4 with (CH,)3NO and a catalytic amount of 0s04 (13, 224-225) yields essentially a single triol (5). Finally, a Pum-merer rearrangement of the sulfoxide followed by reduction of an intermediate... 

Oikawa and Yonemitsu reported a general method for the synthesis of 2-hydroxy-carbazoles (529) by the acid-catalyzed cyclization of the p-keto sulfoxide 528 (511). The required p-keto sulfoxide was derived from nucleophilic attack of dimethyl sulfoxide on methyl 3-indolepropionate. 

The key step in this synthesis is an intramolecular nucleophilic attack on the electron-rich indole nucleus by the carbocation derived from the p-keto sulfoxide in the presence of acid. Finally, the intermediate tetrahydrocarbazole aromatizes by elimination of methanethiol under the conditions of the reaction to produce the hydroxycarbazole (511) (Scheme 5.12). 

Acylation of active hydrogen compounds followed by cleavage 0-109 Reduction of p-keto sulfoxides 0-110 Acylation of carboxylic acid salts followed by cleavage... 

Diastereoselective reduction of chiral -keto sulfoxides (11,291-292). Chiral p-keto sulfoxides 1, prepared by reaction of p-(tolylsulfinyl)methyllithium with esters, are reduced by DIBAH in THF diastereoselectively to (R,S)-2. In the presence of ZnCl2, the opposite diastereoselectivity obtains. The paper includes a new method for conversion of these p-hydroxy sulfoxides into chiral epoxides.1... 

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-... 

Diastereoselective reduction of chiral p-keto sulfoxides.1 The chiral /i-keto sulfoxides (I) are reduced by LiAH4 and several borohydrides mainly to 2. The stereoselectivity is increased as the temperature is lowered. In contrast, DIBAH and diborane reduction results mainly in the alcohol 3. 

Trichloromethyltitanium (10, 270 12, 355 13, 216). Diastereoselective addition to the chiral p-keto sulfoxide (1) is difficult because of ready enolization in the presence of a base. However, this titanium reagent reacts with marked dias-tereoface selectivity, which is the opposite of that observed with (CH,),A1. Similar... 

Stereoselective reduction of -keto sulfoxides. The reduction of the P-keto sulfoxide 1 with NaBH, in CH,OH/aq. NH, (9 1) proceeds with efficient 1,3-asymmetric induction and epimerization at C, (equation 1). Only slight stereoselectivity obtains in a neutral medium. The chirality of the sulfinyl group has no effect. 

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). 

By condensation of the dianion of r-butyl acetoacetate and (—)-menthyl (S)-p-toluenesulfinate, the corresponding p-keto sulfoxide was obtained in high yield (eq 15) and shown to be an efficient... 

Synthesis of P-Keto Sulfoxides. Optically active p-keto sulfoxides are very useful building blocks (eq 4) because they can be stereoselectively reduced to afford either diastereomer of the corresponding p-hydroxy sulfoxide under appropriate conditions (Diisobutylaluminum Hydride or Zinc ChloridefDlBALf and thus give access to a wide variety of compounds chiral carbinols by desulfurization with Raney Nickel or LithiumJethyhmme ini the case of allylic alcohols epoxides via cyclization of the derived sulfonium salt butenolides by alkylation of the hydroxy sulfoxide 1,2-diols via a Pummerer rearrangement followed by reduction of the intermediate. ... 

Numerous applications to total synthesis of natural products have been reported. In the case of the macrolide (i )-lasiodiplodin, the achiral ester (eq 5) was reacted with the (+)-(i )-methyl p-tolyl sulfoxide derived anion to give the corresponding p-keto sulfoxide, which was then reduced with DIBAL to give, after desulfurization, the seco-ester of (i )-lasiodiplodin (eq 5). This is an example showing that the chirality can be introduced at the end of the synthesis in the desired configuration. 

Methyl chloroacetate reacts with the anion of (7 )-methyl p-tolyl sulfoxide to give the corresponding 8-chloro-p-keto sulfoxide (eq 10), which can be easily transformed into the corresponding 3-hydroxy sulfoxide which gives, in presence of a base, the optically active a-sulfinyl epoxides. As illustrated here, a-sulfinyl epoxides can be opened by cuprates, leading to chiral homoallylic alcohols. ... 

An impressive new route to enantiopme syn- and anft-1,2-diols involves sequential diastereoselective DIBAL reduction of oxalyl-di(iV-methyl-7V-methoxyamide) following conversion to a corresponding intermediate P-keto sulfoxide a route that involved control of both reductions by the chiral sulfoxide auxiliary. Comparison of P-hydroxy ketone systems with the y-sulfoxide-) -keto systems used here showed this to be the first example of such asymmetric induction by a y-sulfoxide substituent. 

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. 

Another way of preparing ketones involves alkylation of p-keto sulfoxides... 

Solladie, G, Demailly, G, Greek, C, Reduction of P-keto sulfoxides a highly efficient asymmetric synthesis of both enantiomers of allylic alcohols, J. Org. Chem., 50, 1552-1554, 1985. 

P-Keto sulfoxides. TAS-F promoiei 5-aryl arenethiosulfonate 5-oxides. 

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