Dioxolanones chiral

Menthone-Derived Dioxolanones Chiral Glycolic Acid Derivatives. Acetalization of menthone and phenylmenthone with glycolic acid leads to chromatographically separable mix-... 

Dutton reported on the synthesis of an e-caprolactam analog of an anthelmintic cyclic peptide. The a-hydroxy-e-caprolactam 44 was generated in an ex chiral pool synthesis staring from malic acid. The a-hydroxy carboxylic acid unit was protected as a dioxolanone in 43. The protective group served simultaneously as the reactive function during cyclization lactam 44 formation succeeded by ring opening of the dioxolanone 43 by the nucleophilic attack of the amino function, Eq. (8) [14]. 

A patent procedure for formation of compounds 19 from simple tartaric acid derivatives has appeared <06USP047129> and various new routes to chiral dioxolanones include synthesis of dioxolan-2-ones either by transition metal-mediated asymmetric synthesis <06T1864> or enzyme-mediated kinetic resolution <06H(68)1329> and a new synthesis of the chiral dioxolan-4-ones 21 from lactic or mandelic acid involving initial formation of intermediates 20 with trimethyl orthoformate in cyclohexane followed by reaction with pivalaldehyde <06S3915>. 

The stereoselective introduction of both benzyl groups simultaneously in one step seemed to be particularly attractive for a short synthesis of a- hy-droxylated lactone lignans from malic acid (99). Such a simultaneous double alkylation requires the formation of a chiral l,3-diene-l,4-diolate, which was not known. On the other hand, achiral 1,3-diene-1,4-diolates (di-enolates) have been previously prepared by Garrett et al. [58] and subsequently employed for the synthesis of racemic lignans by Snieckus [59] and Pohmakotr [60]. With knowledge of the synthesis and reactivity of di-enolates, we planned to prepare chiral di-enolates from dioxolanones and to alkylate these di-enolates in a stereocontrolled manner (Scheme 22). For the development of the described double deprotonation/alkylation strategy, tert-hutyl... 

Narasaka et al. demonstrated the utility of titanium-ligand complexes in the resolution of chiral a-aryl esters [52]. Ti(Oi-Pr)4-ligand 56 complex resolves 2-pyridine thioesters with high selectivities (fcrei=26-42, see Scheme 13). Seebach and co-workers have examined titanium-TADDOLate complexes as reagents for the ring opening of meso anhydrides, dioxolanones, and azalactones [53]. Addition of an achiral isopropoxide source renders the desymmetrization of meso... 

It is often very useful to be able to alkylate a readily available chiral a-hetero-substitut-ed carboxylic acid in an enantiospecific manner, as a means of using the chiral center and at the same time building-up the rest of the target carbon skeleton. Such a reaction has been devised by Seebach and coworkers524. In this process a-hydroxy- and a-mercaptocar-boxylic acids were first reacted with pivaldehyde, to produce a 1,3-dioxolanone or 1,3-oxathiolanone. This was followed by reaction with base and alkylation by an alkyl halide and subsequent hydrolysis to regenerate the hydroxyl or mercapto group (equation 70). The product was obtained in greater than 95% ee. Similar reactions with other electrophiles were also successful. 

R)- and (S)-f-Butyl-5-methylene-l,3-dioxolan-4-one, a Chiral a-Alkoxy Acrylate. It is also possible to introduce an ex-ocyclic double bond onto the dioxolanone ring, as in compounds (9)-(ll), derived from lactic and malic - acids. These a,3-unsaturated carbonyl derivatives are acceptors for radical additions and undergo cycloadditions with dienes and heterodienes. The Diels-Alder adduct (12) of ent-(9) with cyclopentadiene is formed with exo selectivity (96 4) and serves as aprecursor to norbomenone (13). Cycloadduct (14), obtained from methylenedioxolanone (9) and an open-chain triene, is also the result of an exo addition and is used in tetronolide synthesis. ... 

Lynn Power was born in Co. Wexford, Ireland. She completed a B.Sc. degree at the National University of Ireland, Maynooth in 2004, including a final year research project with Dr. Frances Heaney. She was the recipient of the Kathleen Lonsdale Prize for the best student graduating in chemistry. She then carried out Ph.D. work at the University of St. Andrews in the area of asymmetric synthesis using chiral dioxolanones under the supervision of Dr. Alan Aitken. 

A number of important synthetic methods involving deprotonation of dioxolane and dioxolanone systems followed by stereoselective reaction with an electrophile have been developed. Thus, the tartrate-derived chiral dioxolanes (131) can be deprotonated and alkylated to afford mainly (132) <81AG(E)1030>, while the related cis compounds (133) similarly give (134) with a selectivity of up to 95% <82AG(E)449, 83CB3413) (Scheme 6). Deprotonation and reprotonation of the chiral cyano-dioxolanes (135) results in deracemization to give the trans products (136) (Equation (17)) <89TL5157>. 

This method was proposed by P. Husek (ref. 5) and involves the analysis of the lactic acid in the form of dioxolanone using GC on a chiral stationary phase comprising a derivative of the p-cyclodextrine heptakis (2,3,6 tri O methyl) p-cyclodextrine. The derivatization reaction is as follows ... 

Aldol reactions of chiral dioxolanones (113) and (114) are summarized in Scheme 6 and Table 9. ° With both (113) and (114), essentially perfect diasterofacial selectivity is observed. The simple dia-stereoselection is modest to good, and is dependent on the enolate counterion. For the lithium and magnesium enolates, the sense of simple diastereoselection is the same as is observed with the achiral dioxolanone (107) and the chiral dioxolanone (110). Use of the zirconium enolate generally reverses the sense of simple diastereoselection, although the isomer ratios are not very high in some cases. 

Cyclic exo-methylene compounds bearing a chiral acetal function prove to be excellent dieno-philes in the noncatalyzed Diels-Alder reaction. Dioxolanones 8 react with cyclopentadiene (9) and acyclic dienes 12 and 15 to afford adducts with diastereoselectivities as high as 100% 28,29. The major adduct 16 from the addition of 8b to diene 15 has been applied to the synthesis of the top half of kijanolide30. 

Chiral dioxolanone 71 and oxazolidinone 72 alkenes, which can be readily prepared from lactic acid or alanine, respectively, undergo diastereoselective radical... 

Esters of a chiral rrans -2-(2-naphthalenesulfonyl)cyclohexanol undergo alkylation with excellent diastereofacial (hence enantiomeric) selectivity. Glycolic acid is transformed into chiral homologues via formation of 1,3-dioxolanone with IV.A -diisopropyl-10-camphorsulfonamide and subsequent alkylation.- ... 

An alternative way to exploit the steric screening principle in the elaboration of chiral a-hydroxy-esters is by asymmetric alkylations of the dioxolanones (140) and (141) [R=H] derived in a... 

Both enantiomers of frontalin, an aggregation pheromone of the Western pine beetle, have been synthesized using chiral dioxolanones derived from (S)- or (i )-lactic acid [23]. Alkylation of 56 with the dimethyl acetal of 5-iodo-2-pentanone affords trisubstituted dioxolanone 67 in high yield. Reductive cleavage of the hetero ring followed by acid-catalyzed trans-acetalization leads to (R)-( + )-frontalin (69) in 73% overall yield from (S)-( + )-lactic acid... 

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