Diols from hydroxy-ketones

Anri-diols can be formed from -hydroxy ketones using Tin(IV) Chloride or BF3-OEt2. The hydroxy ketones are silylated, treated with the Lewis acid, and then desUylated with Hydrogen Fluoride. 5yn-diols are formed if Zinc Chloride is used as the catalyst. 

Acetylenedimagnesium bromide, 66, 84, 137 Acyl-alkyl diradical disproportionations, 299 Acyl-alkyl diradical recombination, 296 Alkaline hydrogen peroxide, 10, 12, 20 Alkylation of formyl ketones, 93 Alkylation via enolate anions, 86 17a-Alkynyl steroids from 17-ketones, 67 2a-Al]yl-17jS-hydroxy-5a-androstan-3 -one, 9 5 Allylic acetoxylation, 242 Allylmagnesium bromide, 64 17 -Aminoandrost-5-en-3 -ol, 145 17 a-Aminomethy 1-5 a-androstane-3, 1718-diol, 387... 

Now the ether may be disconnected, diol (13) being the obvious starting material. This contains an i-hydroxy ketone so we might consider disconnecting an acyl anion equivalent from a ketone. If we use an acetylene, the starting material (14) is symmetrical so hydration presents no problems,... 

Tetramethylammonium triacetoxyborohydride gives anft -l,3-diols from (3-hydroxy ketones.136 These reactions are thought to occur by a rapid exchange that introduces the hydroxy group as a boron ligand. 

In a first reactor, where benzoylformate decarboxylase (BFD) is retained, benz-aldehyde and acetaldehyde are coupled to yield (S)-hydroxy-l-phenylpropanone. This hydroxy ketone is then reduced to the corresponding diol in a second reactor by an alcohol dehydrogenase (ADH). Regeneration of the necessary cofactor is achieved by formate dehydrogenase (FDH) or by other methods. To avoid additional consumption of redox equivalents by unselective reduction of residual starting material from the first reactor, the volatile aldehydes are removed via an inline stripping module between the two membrane reactors. In this setup the diol was produced with high optical purity (ee, de > 90%) at an overall space-time yield of 32 g L d . ... 

Benzoyl formate decarboxylase from Pseudomonas putida has been used to synthesize chiral 2-hydroxy ketones and bis(a-hydroxy) ketones, which find their use as pharmaceutical intermediates and as new multidentate ligands for asymmetric transition metal catalysis, respectively.272 273 Combining this decarboxylase activity with AdH has allowed all the stereoisomers of 1 -phenyl-propane- 1,2-diol to be synthesized.274... 

Cross-coupling reactions of ArCOAr. Reaction of Yb(0) with diaryl ketones changes the reactivity of the carbonyl group from electrophilic to nucleophilic. Thus in the presence of this lanthanoid metal, diaryl ketones couple with other ketones, nitriles, and epoxides to give pinacols, a-hydroxy ketones, and 1,3-diols, respectively, via the intermediate a. 

Conagenin (39) is a promising anticancer natural product isolated in 1991 from the culture broths of Streptomyces roseosporus20 (Scheme 4.1n). The chelation-controlled Zn(B 114)2 reduction of the p-hydroxy ketone 40 produced the 1,3-syn-diol 41 in 30 1 diastereoselectivity. Protection of the hydroxyl groups gave the bis-acetate 42, which was then subjected to oxidative cleavage to afford the acid 43. 

The 1,3-anti -reduction of (3-hydroxy ketones was utilized in the total synthesis of (+)-roxaticin (14), a pentaene macrolide isolated from streptomycete X-149944 (Scheme 4.2e). The (3-hydroxy ketone 15 underwent 1,3-anti -reduction to afford the diol 16 in 99% yield and greater than 95 5 diastereoselectivity. The resulting diol was then protected as a cyclopentylidene ketal (17) by using cyclopentylidene dimethyl ketal and pyridinium p-toluene sulfonate (PPTS). 

Stereoselective reduction of a y-hydroxy ketone. Reaction of the y-liydroxy ketone 1 with LiAIHj. ZnBHi. or NaBHj yields about equal amounts of the two possible diols. However, reduction 4 ith Li(C,H,),BH (2 cquiv.) yields only one product (2) in yield. The high stereoi-icicctivity is attributed to formation of a chelated boron intermediate that favors attack by the hydride from the (3-facc. The diol (2) is converted by TsCI into ancistrofuran (3), a ddfensive secretion of certain termites. 

Silver carbonate on Celite itself is a highly selective reagent for this type of chemoselective oxidation as can be seen from the examples in Scheme 17 secondary diols can be oxidized to the hydroxy ketones, and primary diols are oxidized to lactones (see Section 2.9.2.2). 

Two methods of end-group construction were used in the synthesis of methyl azafrin [methyl 5,6-dihydroxy-5,6-dihydro-10 -apo-/3-caroten-10 -oate (72)]. The first route used the epoxy-intermediate (73) which on treatment with acid gave the 5,6-diol (74). In the second procedure the trimethylcyclohexanone (75) was converted into the hydroxy-ketone (76) which reacted with the Cg fragment (77) to give the acetylenic compound (78). The Wittig salt (79) was made from either (74) or (78) and used in the condensation to form methyl azafrin. 

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