Copper acetonide

Chiral all-syn-l,3-polyols. A reiterative route to these polyols from an optically active epoxide (1) involves ring opening with a cuprate derived from vinyllithium and copper(I) cyanide (11, 366-367) to give an optically active homoallylic alcohol (2). This is converted into the fepoxide (4) via a cyclic iodocarbonate (3) by a known procedure (11, 263). Repetition of the cuprate cleavage results in a homoallylic 1,3-diol (5). The ratio of desired syn- (o anfi-diols is 10-15 1. This two-step sequence can be repeated, with each 1,3-diol unit formed being protected as the acetonide. The strategy is outlined in Scheme (I). 

Copper catalysis has been shown to have a dramatic effect on regioselectivity in the protection of sugar derivatives as the acetonide [33]. Compound 47 afforded the acet-onide 48 upon treatment with dimethoxypropane and CUSO4 in acetone. In contrast, the acid-catalyzed acetalization afforded 49 in 90 % yield (Sch. 12). It is suggested that the acid-catalyzed reaction occurs first at the primary alcohol and subsequently migrates to the secondary alcohols to afford 49 whereas the copper-catalyzed process is not reversible. 

Dondoni and coworkers [63] have shown that homologation of a-hydroxycarbaldehydes can be achieved with high antiselectivity by addition of 2-(trimethylsilyl)thiazole (42) (Scheme 13.25). For instance, D-glyceraldehyde acetonide (R)-24 reacts with 42 giving 43 in 96% yields with the anti vs. syn diastereoselectivity better than 95 5. Release of the aldehyde requires protection of the alcohol as a benzyl ether, methylation of the thiazole generates intermediate 43 Me that is not isolated but reduced in situ with NaBH4 to give thiazoline 43 H. Mercury(II)-catalyzed hydrolysis liberate the semiprotected D-erythrose derivative d-45 in 62% overall yield [64]. Methylation of the thiazole moiety can also be achieved with methyl triflate instead of Mel, and copper(II)chloride can be used instead of mercury(II)chloride [65]. 

Oxidation. Terminally silylated homopropargylic alcohols give y-lactones. The Wacker oxidation can be carried out using substoichiometric Cu(OAc instead of the copper chloride. This modified procedure is operationally simpler and avoids hydrolysis of acetonide when it is present. 

The crucial step of Overman s approach is essentially a Grewe-type disconnection but involves an intramolecular Heck reaction to complete ring B. An enantioselective reduction of 2-allyl-cyclohexeneone 195 introduced a chiral element. Condensation of the resultant S-alcohol, (196) with phenylisocyanate, oxidation of the sidechain olefin with osmium tetroxide and acetonide protection afforded 198, Scheme 22. A copper-... 

Keinan prepared separately the two fragments (the THF moiety and the Y-methyl-y-lactone) and used, as a key step of his sequence, the asymmetric dihydroxylation (AD-mix.-p), the very efficient Sharpless procedure for the formation of a,(3-diols. Then, the cross-coupling was performed by addition of an alkyne and a vinyl halide in the presence of palladium and copper catalysts (Fig. 6). Treatment of the unsaturated ester 48 (prepared in 4 steps from commercially available starting material, and 65 % overall yield) with AD-mix.-p in rerr-butanol/water (1 1) with methanesulfonamide for 16 h at 0 °C afforded the lactone 49 which possessed 3 carbon atoms out of the 4 with the desired absolute configuration. Inversion of the fourth stereocentre after acetonide... 

Both enantiomers of 3-hydroxy-l,7-dioxaspiro[5.5]undecane (471), the minor component of the olive fly pheromone, can be synthesized from (5)-malic acid via acetonide 454b (Scheme 66) [120]. The initial carbon skeleton is constructed by sequential alkylation of 341 with 454b and then EE-protected 4-iodobutanol. Copper-mediated hydrolysis of the dithiepin ring affords a complex mixture of products, two of which, (3aS, 65)-471 and 472, are isolated in 33% and 18% yields respectively. 

S)-Citramalic acid (1029) is readily reduced to triol 1030 with either diborane [222] or borane methylsulfide-trimethylborate [223]. Conversion of 1030 to acetonide 1031 can be accomplished either with acetone in the presence of a catalytic quantity of perchloric acid (73% yield from 1029) [222] or with acetone [224] or 2,2-dimethoxypropane [223] in the presence of copper sulfate (48% yield from 1029). Oxidation of the alcohol with pyridinium chlorochromate furnishes aldehyde 1032 in 72% yield [223]. 

The absolute stereochemistry of the C-12 and C-13 oxirane moiety of laureoxolane (157), a colorless unstable bromoether obtained from extracts of Laurencia nipponica, was determined on the basis of a chiral synthesis of 156, a degradative derivative of 157. The C-5 to C-8 unit with two asymmetric centers at C-6 and C-7 of 157 corresponds to (25, 35)-l-benzyloxy-3,4-epoxy-2-butanol (142). Elongation of 142 using butyllithium and copper cyanide followed by the creation of a new epoxide provides 152. Lithium acetylide ethylenediamine complex addition to 152 and subsequent ketalization affords the acetylenic acetonide 153, which is coupled with (2i ,35)-l,2-epoxy-3-benzoyloxypentane (154) to furnish 155. Subsequent five-step transformation of 155 provides 156 [60] (Scheme 37). 

Anhyd copper sulfate is also an excellent catalyst for the formation of acetonides from glycols and acetone (eq 2). Either 2,2-dimethoxypropane or 2-methoxypropene can sometimes improve the efficiency. The regiochemistry of the copper-catalyzed process is different from that found in the proton-catalyzed reaction. 

Addition to n-Glyceraldehyde Acetonide Preparation of Epoxy Alcohols and n-Threose Derivatives. 2,3-0-isopropylideneglyceraldehyde (5) reacts with (1) in the presence of excess (2) to give the syn addition product (6) with high di-astereoselectivity (>98 2 syn anti, eq 3). Sharpless epoxida-tion of (6) followed by protodesUylation gave epoxy alcohol (7) (eq 4). Alternatively, (6) can be converted to the D-threose derivative (8) by a sequence of three steps protodesUylation, protection, and ozonolysis. Replacement of copper(T) cyanide and methyl-lithium for Cul in this reaction gives predominantly the anti addition product in 87% yield. 

Weiss and Mingioli established the structure of shikimic acid-3-phosphate, an intermediate on the shikimate pathway, as (4) by a comparison with a synthetic sample of shikimic acid-S-phos-phate (17) prepared from (9), Figure 2.1. Both acids reacted with periodic acid to show the presence of an a-glycol grouping but the dialdehydes formed in this reaction had markedly different spectral characteristics. The presence of a cis a-glycol grouping in (17) was confirmed by the relatively rapid reaction with periodate and the formation of a copper complex and an acetonide derivative. In contrast the natural phosphate ester (4) reacted slowly with periodate and did not form a complex with copper acetate nor an... 

Opening of this epoxide in a copper-catalyzed Grignard reaction led to this cis-diol 366, which was easily characterized and purified by an acetonide. 

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