Hemiketals from alcohols + ketones

The formation of hemiketals and ketals from alcohols and ketones is exactly analogous (with somewhat more difficulty as ketones are generally less reactive than aldehydes Chapter 9). In the reaction of a ketone, such as cyclohexanone (Table 8.6, item 12) with a 1,2-diol, such as 1,2-dihydroxyethane (ethylene glycol [HOCH2CH2OH]) (Scheme 8.52), the second equivalent of alcohol is part of the initial alcohol substrate and the cyclic product results. 

Organic chemists originally used hemiketal and ketal for describing the products from alcohol addition to ketones and hemiacetal and acetal were used for the products from alcohol addition to aldehydes.The lUPAC system has dropped the hemiketal and ketal names in favor of using hemiacetal and acetal for the species formed from both aldehydes and ketones. We will not use hemiketal or ketal, but be alert, because one still sees these sensible terms occasionally. 

Aldehydes and ketones undergo reversible addition reactions with alcohols. The product of addition of one mole of alcohol to an aldehyde or ketone is referred to as a hemiacetal or hemiketal, respectively. Dehydration followed by addition of a second molecule of alcohol gives an acetal or ketal. This second phase of the process can be catalyzed only by acids, since a necessary step is elimination of hydroxide (as water) from the tetrahedral intermediate. There is no low-energy mechanism for base assistance of this... 

If you look in older texts, you may still see the terms hemiketal and ketal. At one time, four terms were used for the products of alcohols with carbonyl groups hemiacetal, acetal, hemiketal, and ketal. A hemiketal is now a type of hemiacetal and a ketal is now a type of acetal. Originally, acetals and hemiacetals came from aldehydes and ketals and hemiketals came from ketones. The structures of hemiacetals and acetals contained a C-H bond, but ketals and hemiketals did not. 

The generation of hydroxy ketones by the brominolysis of stannylenes has been used several times in total synthesis. Experiment G [see Eq. (15)] describes a key step in the total synthesis of the antibiotic (+)-spectinomycin [12,13]. It is remarkable that the two oxygen atoms bound to the tin atom originate from hydroxyl groups, which are port of different functions, a hemiketal and a secondary alcohol. The oxidation is selective for one alcoholic function ont of three. The same product was obtained by W-bromosuccinimide oxidation of the tributylstarmyl ether. 

Aldehydes and ketones react with alcohols to form hemiacetols and hemiketah, respectively. In this reaction the alcohols react in typical fashion as the nucleophile. When aldehydes and ketones are attacked by a nucleophile, they undergo addition. Aldehydes and hemiacetals, and ketones and hemiketals, exist in equilibrium when an aldehyde or ketone is dissolved in an alcohol however, usually the hemiacetal or hemiketal is too unstable to isolate unless if exists as a ring structure. If a second molar equivalent of alcohol is added, an oceiuf is formed from a hemiacetal, or a ketal is formed from a hemiketal. 

The intermediate formed from this first nucleophilic addition is known as hemiacetal. When ketone is the starting material, the structure obtained is a hemiketal. Once the hemiacetal is formed, it is protonated and water is eliminated by the same mechanism described in the formation of imines with the only difference that oxygen donates a lone pair of electrons to force the removal of water rather than nitrogen (Following fig.). The resulting oxonium ion is extremely electrophilic and a second nucleophilic addition of alcohol to forms the acetal. 

H20 or alcohols as nucleophiles give low molecular weight compounds when they add to the C=0 double bond of carbonyl compounds. These addition products are called aldehyde or ketone hydrates (Section 9.1.1) and hemiacetals or hemiketals (Section 9.1.2), respectively, depending on whether they result from the addition to an aldehyde or a ketone. Today, one no longer distinguishes systematically between hemiacetals and hemiketals, but the expression hemiacetal is frequently used to cover both. 

When this reaction is conducted on ketones, instead of aldehydes, the equivalent species to the hemiacetal and acetal are now called hemiketal and ketal respectively. However, when simple ketones are reacted with normal monofunctional alcohols, the reaction rarely goes to completion, unlike the situation with aldehydes where the reaction proceeds smoothly. Yet, when a 1,2-diol is reacted with a ketone, then the reaction goes to completion much more readily. Write the complete reaction sequence for the formation of the cyclic ketal starting from propanone and 1,2-ethandiol, under acidic conditions. Also, suggest why the product between one molecule of each reagent is favoured over the alternative product that would result from the reaction between two molecules of the diol and one of the ketone. 

K and in the solid state. The cyclic carbonyl ylide (77 R = Ph), obtained by irradiation of 2.3-diphenylnaphthoquinone 2,3-epoxide (78 R = Ph), has been trapped with suitable dipolarophiles. The carbonyl ylide (77 R = Me), derived from the 2,3-dimethyloxiran (78 R = Me) by irradiation in benzene, adds to allyl alcohol to give the hemiketal (79) by way of adduct 80. Other 2,3-dialkylnaphthoquinone 2,3-epoxides undergo similar photo-chemically induced carbon carbon bond cleavages to give dipolar or biradical species that have been trapped in turn with alkenes and ketones ... 

Overman s retrosynthetic analysis is depicted in Scheme 1. Pentacyclic ketone 4, derived from allylic alcohol 7 by an aza-Cope-Mannich rearrangement of formaldiminium ion derivative 6 furnished 3 through the C5 hemiketal disconnection. An intramolecular oxidative coupling of a dienolate generated from indole-... 

For the stereoselective synthesis of C-glycosides, deoxygenation of hemiketals, obtained from Wacker oxidation of sngar-derived olefin alcohols, was envisaged as an easy and efficient protocol. In our earlier study on the synthesis of 4-epiethisolide, attempted PdCV mediated conversion of the terminal olefin (1), obtained from sugar chiron into a methyl ketone (2) resulted in the exclnsive formation of an anti-Markovnikov product (3), which happened to be the first report in the literature (Scheme 22.1). 

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