Keto sulfoxides, reduction

C. Reduction of )3-Keto Sulfoxides with Aluminum Amalgam (//)... 

Enantiomerically pure /J-keto sulfoxides are prepared easily via condensation of a-lithiosulfinyl carbanions with esters. Reduction of the carbonyl group in such /J-keto sulfoxides leads to diastereomeric /J-hydroxysulfoxides. The major recent advance in this area has been the discovery that non-chelating hydride donors (e.g., diisobutylaluminium hydride, DIBAL) tend to form one /J-hydroxysulfoxide while chelating hydride donors [e.g., lithium aluminium hydride (LAH), or DIBAL in the presence of divalent zinc ions] tend to produce the diastereomeric /J-hydroxysulfoxide. The level of diastereoselectivity is often very high. For example, enantiomerically pure /J-ketosulfoxide 32 is reduced by LAH in diethyl ether to give mainly the (RR)-diastereomer whereas DIBAL produces exclusively the (.S R)-diastereomer (equation 30)53-69. A second example is shown in... 

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. 

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... 

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]. 

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... 

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. 

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. 

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. 

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. 

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. ... 

The absolute configuration at C-32 in recently isolated triterpenoids was assigned by reduction of a 3-keto sulfoxide (eq 13). ... 

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. 

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. 

Interestingly, the a-acetoxy sulfides (106) obtained from the reaction of 3-keto sulfoxides with acetic anhydride containing sodium acetate undergo in situ oxidation-reduction and acyl transfer, giving a-acetoxy thiol esters (107) as products (Scheme 23)J Yields in this process are generally high. 

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°. 

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). 

The reduction of a diastereomeric mixture of enantiomerically pure /3-keto sulfoxides (7) furnished one of the four possible isomers with good overall stereoselectivity (90%), when carried out under conditions which favor epimerization of the a chiral center (eq 16). This outcome derives from a chelation-controlled reduction (involving the sulfoxide oxygen) coupled with a kinetic resolution of the two diastereoisomers of (7). ... 

Chiral sulfoxides have been extensively employed as asymmetric auxiliary group that assist stereoselective reactions. The sulfoxide functional group activates adjacent carbon-hydrogen bonds to allow proton abstraction by bases, and the corresponding anions can be alkylated [1176] oracylated [1177] with high diastereo-selectivity. Similarly, thermal elimination [1178] and reduction of a-keto sulfoxides [1179] can proceed with transfer of chirahty from sulfur to carbon. In spite of... 

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