Lactols dialdehydes

An application of this strategy to the synthesis of the antifungal metabolite ( )-avenaciolide 182 is shown in Scheme 4183. The photoadduct in this case, 178, was hydrogenated and hydrolyzed to give 179. Reaction of 179 with vinylmagnesium bromide and subsequent manipulation afforded aldehyde 180, which could be transformed via ozonol-ysis, epimerization of the dialdehyde and acidification of the dialdehyde acetonide to protected bis(lactol) 181. Oxidation and methylenation then afforded the desired target 182. 

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. 

A convenient route to 1,4-monoprotected dialdehydes, 1,4-ketoaldehydes, y-lactols and v-lactones through radical alkylation of a,p-unsaturated aldehydes in organic and, organic-aqueous media. Tetrahedron, 59, 947-957. 

The group-selective aldolization/desymmetrization of w -dialdehyde with a boron enolate of TV-propionylsultam yielded lactols with simultaneous generation of four stereogenic centers. Oxidation followed by saponification of the sultam moiety provided the Prelog-Djerassi lactonic acid in 61-71% overall yields (Equation (183)).689... 

This procedure is an adaptation of a photoannulation reaction, originally developed by de Mayo ( ref 22 ) and leads initially to the stereoselective formation of a cyclobutanol ring (intermediate 44 ) which undergoes a spontaneous ring opening to the typical iridoidic dialdehyde ( intermediate 45 ) which is theoretically in equilibrium with the lactol iridoidic moiety ( intermediate 46 ), as depicted in the scheme 9. 

Iridoids, a widely occurring class of heterobicyclic monoterpenes, are derived from 2-hydroxy-3,4-dihydro-2//-pyran with a 3,4-fused methylpentane ring. Iridodial 15 is the parent system. As an enol lactol, it is in equilibrium with a dialdehyde ... 

Dioxolanone 58c, when reduced to lactol 61, is a masked 1,4-dialdehyde (64) equivalent. The aldehyde, which is freed by ozonolysis and acidic hydrolysis, undergoes a Marschalk reaction with leucoquinizarine (65) to give rhodomycinone 66 in 45% yield [22] (Scheme 9). 

With dialdehydes as enol components, the aldol reaction may be followed by an acetalization event Thus, Hayashi and coworkers [10] established a highly enan-tioselective proHne-catalyzed domino aldol-acetalization of aqueous tetrahydro-2H-pyran-2,6-diol (21) and aldehydes (Scheme 8.7). In this sequence, the intermediate aldolate product 22 is trapped by the additional aldehyde moiety to generate a lactol, which through addition of methanol and acid is converted into the double acetal 23. 

Many of these organocatalyzed domino reactions are initiated by an enantioselective Michael addition followed by an acetalization. The first example of such transformation was reported by Mangion and MacMillan [26] in 2005 as a key step for the total synthesis of brasoside and littoralisone (Scheme 16.12). Using (S)-proline, the dialdehyde underwent contra-thermodynamic diastereoselective Michael/acetalization for the formation of the desired lactol in good yield. 

De Brabander et al. have reported a very rapid enantioselective synthesis of the Prelog-Djerassi lactonic acid through an asymmetric aldol reaction [88] (Scheme 44). The Oppolzer sultam-derived A-propionyl derivative 215 was used to desymmetrize meso-dialdehyde 216, and the diastereoselectivity was found to be 80 %. Oxidation of the resulting lactol 217 to lactone 218 was followed by oxidative removal of the chiral auxiliary. The unwanted diastereoisomer resulting from the aldol reaction was removed chromatographically after the oxidation step. 

Cossy et al. have developed a stereoselective approach for the synthesis of 8-lactones by desymmetrization of /neso-dialdehydes with optically active cyclopentadienyldialkoxyallyltitanium complexes [93] (Scheme 49). Addition of the (S,S)-236 TADDOL complex to aldehyde 235 gave the corresponding lactols, which on oxidation with TPAP/NMO led to lactones 237 and 238 in excellent yields and with good diastereoselectivity. Similarly, addition of the (RJi)-236 TADDOL complex to aldehyde 235 provided the opposite two enantiomers in moderate yield and with similar diastereoselectivity. 

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