Dioxolanones, synthesis

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... 

Since the formation of optically active, dioxolanone-based di-enolates was not successful, a consecutive alkylation strategy was developed for a short synthesis of (-)-wikstromol (ent-3) from (-)-malic acid (99) (Scheme 25). The first alkylation reaction was analogous to that reported for the enantioselective total synthesis of (-)-meridinol (97). In order to avoid a reduction/re-oxidation sequence and an almost unselective second alkylation, two disadvantages of the synthesis of meridinol (97) [55], we planned to use a different strategy for the second alkylation. Therefore, we have focused our strategy on two stereoselective alkylation reactions, one of dialkyl malates and one of a dioxolanone prepared thereof. Both alkylation reactions were previously described by Seebach and coworker [56, 63, 64]. The... 

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 large number of new reports of reactions of this type have appeared, the majority of which involve reaction between a 1,2-diol or equivalent and an aldehyde, ketone, or other component that supplies C-2 of the resulting dioxole ring. Synthesis of aromatic fused dioxoles will be considered first before dioxolanes and dioxolanones. 

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. 

Eremantholide A (74), a member of the fiiranoheliangolides, has been synthesized in 21 steps starting from 56 [24]. The early part of the synthesis is outlined in Scheme 11. Alkylation of 56 with 2,3-dibromopropene affords the (2 S, 4/ )-dioxolanone 70 (> 98% de) and reaction with Tebbe reagent produces 71. The bromide is converted to a mixed cuprate, and the organometallic is added in a 1,4-fashion to butenolide 72, which is derived from D-mannitol. 

Dixneuf reported using the ruthenium catalyst 25 in the synthesis of enol ethersfrom alkynes and carboxylic acids. Both formation of enol esters by Markovnikov addition of a carboxylic acid to a terminal alkyne (Eq. 9) and formation of dioxolanones (Eq. 10) was successful. In both cases the reactions were carried out homogeneously at 100 °C and the catalyst was recovered by cooling. Filtration led to recovery of the catalyst which was successfully recycled multiple times, as shown by experiments where a single 0.1 mmol sample of catalyst was used to prepare over 50 mmol of a mixture of enol esters using different carboxylic acids and different alkynes in a series of sequential reactions with different substrates and the same catalyst sample. 

Ramage and coworkers (537) have developed a biomimetic synthesis of pulvinic acids which relies for its success on the facility with which dioxolanones of type (110) undergo nucleophilic attack at the lactone carbonyl group with subsequent extrusion of cyclohexanone. In the synthesis of xerocomic acid (Scheme 15) the dioxolanone (110), obtained as the predominant isomer from reaction between the phos-phorane (109) and methyl (3,4-dibenzyloxyphenyl)glyoxalate, was cleaved with the lithium enolate of /-butyl (4-benzyloxyphenyl)acetate. The intermediate dianion (111) probably exists at first as the chelate (112) which is then broken down on aqueous work up and subsequently cyclised specifically at the less hindered carbonyl group to produce the ester (113). The dianion (111) is analogous to the hypothetical... 

The unambiguous synthesis of 3, 4, 4-trihydroxypulvinone (115) has more recently been reported by Ramage and coworkers (Scheme 17) 536). By cleavage of the dioxolanone (117) with the lithium enolate of methyl (4-benzyloxyphenyl)acetate at —78° C the bright yellow carboxylic acid (118) was obtained in hydrated form after work up. Attempts to purify (118) brought about efficient lactone formation. Final-... 

Ramage, R., G.J. Griffiths, F.E. Shutt, and J.N.A. Sweeney Dioxolanones as Synthetic Intermediates 2. Synthesis of Tetronic Acids and Pulvinones. J. Chem. Soc. (London) Perkin Trans. I 1984, 1539. 

The lithium enolate of R,R-tartrate acetonide (11) is another easily accessible chiral molecule and has been alkylated by reactive electrophiles (allyl and benzyl halides) with excellent stereospecificity (>80%). This approach has been used in the synthesis of piscidic acid (12). Similarly, the dioxolanones (13) (from pivalaldehyde and 5-lactic acid) and (14) (from mandelic acid), and the... 

Ramage R, Griffiths GJ, Sweeney JNA (1984) Dioxolanones as Synthetic Intermediates. Part 3. Biomimetic Synthesis of Pulvinic Acids. J Chem Soe Perkin... 

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