Lactones hydroxyaldehydes

Epoxides provide another useful a -synthon. Nucleophilic ring opening with dianions of carboxylic acids (P.L. Creger, 1972) leads to y-hydroxy carboxylic acids or y-lactones. Addition of imidoester anions to epoxides yields y-hydroxyaldehyde derivatives after reduction (H.W. Adickes, 1969). 

Oxazine ring in 212 was formed by spontaneous lactonization in the hydrolysis of 3-aza-5-hydroxy ester 265 (Equation 22) <2005SL693>. The same method was used in the synthesis of 219 <1993LA477>. Oxazine 267 was formed in the hydrolysis of a 3-aza-5-hydroxyaldehyde diethyl acetal 266 <1981JHC825> (Equation 23). 

A naive look at the product suggests an oxidation to a ketone followed by a Baeyer-Villiger like reaction. The product is best explained by a fragmentation from an intermediate chromate ester, resulting on an aldehyde and a stabilized tertiary carbocation that is transformed into a tertiary alcohol by reaction with water. The hydroxyaldehyde so obtained may evolve to the final lactone either via a lactol or a hydroxyacid. 

Very often, when the treatment of a 1,4- or a 1,5-diol with PDC leads to the initial formation of a hydroxyaldehyde that can equilibrate with a cyclic hemiacetal, the latter is further oxidized to a lactone.168... 

The expected hydroxyaldehyde is obtained accompanied by a lactone, resulting from the oxidation of a lactol equilibrating with the hydroxylaldehyde. 

No further oxidation to lactone occurs for the resulting hydroxyaldehyde is not able to equilibrate with a substantial amount of lactol, that would have to exist in a very unfavourable chair conformation containing a bridgehead alkene. 

The intermediate hydroxyaldehyde equilibrates with a sufficient proportion of seven-membered lactol, so that the oxidation of the latter to lactone is more predominant than the oxidation of the intermediate hydroxyaldehyde to dialdehyde. 

PCC sometimes transforms 1,4-diols in to 7-lactones however, at least one of the alcohols in 1,4 diols should be a primary alcohol.297 This oxidation proceeds via an intermediate 7-hydroxyaldehyde that equilibrates with a lactol, which is transformed in a 7-lactone. 

The oxidation of the primary alcohol yields a hydroxyaldehyde that equilibrates with a lactol, which is further oxidized to a 8-lactone. 

TPAP oxidizes lactols to lactones.85 Treatment of 1,4- and 1,5-diols with TPAP, in which one of the alcohols is a primary one, leads to an intermediate hydroxyaldehyde that normally is transformed into a lactone86 via an intermediate lactol. No transformation into lactone occurs when the formation of the intermediate lactol is not permited by geometric constraints.87... 

Lactols are easily transformed into lactones in TEMPO-mediated oxidations.49 When the oxidation of a diol leads to a hydroxyaldehyde that is able to equilibrate with a hemiacetal, the latter is further oxidized to a lactone.50 Interestingly, as TEMPO-mediated oxidations can be very selective in favouring oxidations of less hindered alcohols, lactone formation from diols can be very regioselective.500... 

A corollary of this selectivity is the very easy transformation of diols into lactones with silver carbonate on Celite .16 During the oxidation of a diol with Fetizon s reagent, as soon as an intermediate hydroxyaldehyde is able to equilibrate with a certain proportion of hemiacetal—even if present... 

Ref. 5b IBX performs the selective oxidation of a primary alcohol, leading to a hydroxyaldehyde that is isolated as a lactol that, interestingly, does not suffer a further oxidation to a lactone. ... 

When a TEMPO-mediated oxidation of an 1,4- or 1,5-diol leads to an hydroxyaldehyde able to equilibrate with a lactol, the lactol is normally further oxidized to a lactone.7... 

Normally, lithium aluminum hydride is too vigorous a reagent for the reduction of lactones to the he-miacetal (hydroxyaldehyde lactol) stage, but, in certain circumstances under carefully controlled conditions, it can be used successfully. Usually, lactones give diols with LiAlH4 but, with 0.25 equiv., hemiacetals have been prepared from -y-lactones in high yield (Scheme Sodium bis(2-meth-... 

Diisobutylaluminum hydride (DIBAL) is a reliable reagent for the reduction of lactone 29 to the corresponding lactol 67. This is due to the formation of stable tetrahedral intermediate 66, which prevents further reduction (via hydroxyaldehyde 68 to the diol) and decomposes during aqueous workup to provide the desired lactol 67. 

Lactones are in principle reducible to hydroxyaldehydes, and when applied to lactones of sugar acids the method works well because cyclic acetal or ketal formation stabilizes the carbonyl function and prevents overreduction [3,96-100]. In particular, d-ribose may be prepared from the cathodic reduction of D-ribono-y-lactone as in Eq. (24) the optimum conditions for this reaction include careful buffering of the electrolyte [97-100]. 

SiajBH reduces lactones to lactol borates, which, after hydrolysis, give 7-hydroxyaldehydes [BK5] (Figure 3,53),... 

Glucose, of which many of the chemical reactions actually involve the small concentration of acyclic polyhydroxyaldehyde in equilibrium with the cyclic forms, hemiacetals containing a tetrahydropyran this illustrates the inherent stability of chair conformers of saturated six-membered systems. The propensity for cyclisation is a general one 5-hydroxyaldehydes, -ketones and -acids all easily form six-membered oxygen-containing rings — lactols and lactones respectively. 

As a rule of thumb, oxidation of the (S)- or pro-(S ) hydroxyl group occurs selectively with HLADH (Scheme 2.143). In the case of 1,4- and 1,5-diols, the intermediate y- and 8-hydroxyaldehydes spontaneously cyclize to form the more stable five- and six-membered hemiacetals (lactols). The latter are further oxidized in a subsequent step by HLADH to form y- or 5-lactones following the same (S)-or pro-(5) specificity [1035]. Both steps - desymmetrization of the prochiral or meso-diol and kinetic resolution of the intermediate lactol - are often highly selective. By using this technique, enantiopure lactones were derived from... 

In these oxidations the use of hydrated CUSO4 is mandatory. In fact, it was found that addition of catalytic amounts of water to the solid oxidant creates a more reactive oxidant for the synthesis of lactones from hydroxyaldehydes (eq lO). Small quantities of aqueous t-butanol added to the solid oxidant permit the direct conversion of alkenes to a-hydroxy ketones anda-cUketones (eq 11). Normally, alkenes are inert to the solid oxidant. These differences are attributed to the formation of a thin aqueous... 

Hydrogenation in alcoholic acid converts ketones into ethers Good yields of aldehydes from esters as well as hydroxyaldehydes from lactones can be obtained by reduction with NaAlH4 at low temp. The preparation of aldehydes under mild conditions by cleavage of p-dimethylaminophenlycarbinols with diazotized sul-... 

---