Y-lactols synthesis

It has been demonstrated by Pancrazi, Ardisson and coworkers that an efficient kinetic resolution takes place when an excess (2 equivalents) of the racemic titanated alkenyl carbamate rac-334a (R = Me) is allowed to react with the enantiopure )-hydroxyaldehyde 341 or alternatively the corresponding y-lactol 340, since the mismatched pair contributes to a lower extent to the product ratio (equation 91) . Under best conditions, the ratio of the enantiomerically pure diastereomers 3,4-anti-4,5-syn (342) and 3,4-anti-4,5-anti (343) is close to 14 1. Surprisingly, approximately 9% of the iyw,iyw-diastereomer 344 resulted when the starting (ii)-crotyl carbamate was contaminated by the (Z)-isomer. The reasons which apply here are unknown. Extra base has to be used in order to neutrafize the free hydroxy group. The pure awft, awfi-product 345 was obtained with 85% yield from the reaction of the (W-oxy-substituted titanate rac-334b and lactol 340. 345 is an intermediate in the asymmetric synthesis of tylosine . ... 

Not surprisingly, carbonyl compounds are excellent reaction partners for the ester enolates 104. Since the primary adducts are only isolable in singular cases and the subsequent ring opened products (y-lactols) are very versatile precursors for synthesis of heterocycles, these addition reactions as well as those of electrophiles with a S = C unit will be discussed in a separate paragraph (see section 4.6). 

The synthesis of dihydrofuran derivatives such as 177 has been performed to explore scope and limitations of the Lewis acid promoted hydroxyalkylation of siloxycyclopropanes. Table 6 shows that aromatic as well as aliphatic ketones can efficiently be incorporated. Enolization of ketones does not occur and a 1-methyl group at the cyclopropane is no obstacle for the reaction, which now binds the carbonyl compound to a quartemary center with surprisingly high efficiency (entry 5). Albeit there are some restrictions with regard to the substitution pattern of the cyclopropanes, bicyclic siloxycyclopropanes also give good yields (e.g. entry 6 and Eq. 76). Further examples of the tetrahydrofuran synthesis from intermediate y-lactols with... 

In this reaction only the cyclopropane ring is opened to form III/66. This compound is in equilibrium with the y-lactol III/67, which, in case of R=H, was transformed oxidatively (pyridinium chlorochromate) to the furanone III/68. The synthesis of thiophene derivatives in a similar reaction is shown in Scheme III/ll, also. 

A bicyclic y-lactol—accessible in a few steps— allows entry into certain vinylcyclopro-panes (equation 117). At high temperature, these suffer a hydrogen shift to 1,4-dienes, which are masked 1,4-dicarbonyl compounds capable of many synthetically valuable selective reactions ". A total synthesis of trisporic acids profits from this approach ". If simple Grignard reagents are added to the y-lactol, manipulation of the resulting cyclopropylcarbinols opens a path to 2-methylenecyclobutanones. ... 

The significant bias that IBX displays towards the relative rates of oxidation of primary and secondary alcohols may also be exploited in other ways. Despite the fact that in general, even mild oxidizing agents readily oxidize secondary lactols to lactones, IBX may be successfully employed in the previously unknown one-step synthesis of y-lactols from both 1,4-bis primary diols as well as from 1,4-primary-secondary diols. Treatment of a 1,4-diol with IBX in DMSO gives the desired y-lactol in good yield with very little over-oxidation to the corresponding lactone. Consequently this is an excellent procedure for the synthesis of y-lactols (eq 5)... 

Schmitt A, Reissig H-U (2000) On the stereoselectivity of y-lactol substitutions with allyl-and propargylsilanes - synthesis of disubstituted tetrahydrofuran derivatives. Eur J Org Chem 3893-3901... 

Fig. 7. Nicolaou s total synthesis oxidation to the y-hydroxy lactol. PDC = pyridinium dichromate, DMP = Dess-Martin periodinane.

Fig. (10). Reductive generation of the lactol unit from a lactone A general synthesis for the 2-hydroxy-2/f-1,4-benzoxazin-3(4/y)-one skeleton...

Aryl-y-lactones. Dutch chemists have reported a method for synthesis of lactones of type (4) with an imidazolyl, pyridyl, or aryl group at the 5-position. The process involves reaction of an aromatic aldehyde or ketone with the Grignard derivative of 2-(2-bromoethyl)dioxolane-l,3 (1). The product (2) is cyclized to a lactol (3) by dilute sulfuric acid (reflux). The final step involves... 

A facile and efficient synthesis of lactols 363 via an oxidative rearrangement reaction of 2,3-epoxy alcohols 362 with [bis(trifluoroacetoxy)iodo]benzene has been reported (Scheme 3.145) [463-465], This hypervalent-iodine-induced oxidative transformation has been utilized in the synthesis of several lactones and in the asymmetric synthesis of the marine y-lactone metabolite (+)-tanikolide [463,464]. 

Later, Ramachary and Sakthidevi reported for the first time the organo-catal)Aic cascade approach to the asymmetric synthesis of functionalised chromans via Barbas-List aldol-acetalisation reaction, as depicted in Scheme 2.28. The reaction of acetone with 2-hydro ybenzaldehyde under trans-4-OH-L-proline-catalysis in NMP as solvent furnished the corresponding aldol/lactol intermediate which upon treatment with p-TSA in methanol in one-pot furnished the selectively frans-2-metho y-2-methyl-chroman-4-ol in 55% yield and 77% ee, as shown in Scheme 2.28. 

For the total synthesis of halichondrin B, Kishi and Duan [11] have developed the preparation of heptoside fragment 21 from t-mannonic y-lactone 19. In this strategy, the Wittig reaction was performed on an anomeric lactol with methoxymethylenetriphenylphosphorane. Osmylation and acetylation yielded the protected i-glycero-i-manno-heptose derivative in 58% overall yield after four steps (Scheme 2.6). 

---