Synthesis of .beta.-hydroxy acids using .alpha.-lithiated carboxylic acid salts

Moersch, G. W.; Burkett, Allan R.

doi:10.1021/jo00807a030

Cited by 62 publications

(17 citation statements)

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“…further exploit the ready availability and interesting functionality of 1, its utility in a general route to a astereomeric p-lactones, and subsequent thermal elimination of carbon dioxide (Scheme 2) seemed the most suitable (4,11,12).…”

Section: C02rmentioning

confidence: 99%

The chemistry of thujone. II. Insect juvenile hormone analogues via acid dianion coupling. The β lactone route

Kutney¹,

McGrath²,

Young³

et al. 1979

Can. J. Chem.

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. Can. J. Chem. 57, 3145 (1979).Several stereoselective syntheses of (E)-2-ethyl-6-methyl-5-octenoic acid (17) are described. The dianion of pure 17 was subsequently coupled with (E)-a-thujaketonic acid methyl ester (5), derived from thujone (I), to give the a-lactones 45 and 46 which were then epoxidized and pyrolyzed exemplifying a route to juvenile hormone analogues such as 51 and 54.JAMES P. KUTNEY, MICHAEL J. MCGRATH, ROBERT N. YOUNG et BRIAN R . WORTH. Can. J. Chem. 57.3145 (1979).On dCcrit plusieurs syntheses stCrCosClectives de I'acide (E)-Cthyl-2 methyl-6 octene-5 oique. Le dianion pur de 17 coup16 a I'ester methylique de l'acide (E)-[j-thujacktonique (5) provenant de la thujone (1) separating the E-and Z-isomers (at C6) formed dur-13 SCHEME 1 ing the coupling.Thus, in order to circumvent these difficulties it was necessary to devise an alternative route which, ideally, would fulfill four important requirements: 'Although thujone exists in two epimeric forms at C4, oxidative cleavage to 2 destroys this chiral centre thus allowing crude thujone to be used for this work.internal unsaturations, (ii) a mode of coupling that would allow at least selective trans-isomer formation, (iii) facile separation of the isomeric alkenes, (iu) specific protection of the internal double bond so as to allow specific epoxidation at ClO(11). Of the various methods available (3-101, that involving coupling between a carboxyiic acid dianion and a ketone to give a P-hydroxy acid, generation of di-

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Section: C02rmentioning

confidence: 99%

The chemistry of thujone. II. Insect juvenile hormone analogues via acid dianion coupling. The β lactone route

Kutney¹,

McGrath²,

Young³

et al. 1979

Can. J. Chem.

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“…It is therefore either a direct elimination which c o~~l d occur via an eight-membered transition state 23 (5) or an indirect one, via internal anhydride formation 24 followed by p-lactone 25 and loss of CO, (6 For personal use only. of diketone 8.…”

Section: Synthesis Of the Cyclopropane Diketonementioning

confidence: 99%

“…The mixture was stirred at room temperature for 1 h, acidified with dilute hydrochloric acid to pH 6 …”

Section: Acid Ester 11amentioning

confidence: 99%

“…The organic phase was washed several times with dilute hydrochloric acid and water. Drying and evaporation of the solvent yielded an oil which gave pure acetate acid 15A (2.25 g, 70%); mp 151-153°C (from dichloromethane-ether-pentane); ir v,,, (CHCl,): 3600, 3500 (br), 1724, and 1707 cm-l; nrnr (CDCI,) 6 3 mmol) in pyridine (0.88 ml, 10.9 mmol) and anhydrous benzene (100 ml) was added dropwise during 1.5 h to a cooled solution (0°C) of oxalyl chloride (0.768 ml, 9.0 mmol) in anhydrous benzene (72 ml). The reaction mixture was left for 1.5 h at room temperature.…”

Section: Acetate Acid 15amentioning

confidence: 99%

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Stereospecific syntheses of the α-patchoulene and α-cedrene skeletons from a common intermediate

Deslongchamps¹,

Lafontaine²,

Ruest³

et al. 1977

Can. J. Chem.

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. Can. J. Chem. 55, 41 17 (1977).The synthesis of the cyclopropane diketone 3 and its specific conversion into the tricyclic enedione 4 (cedrene skeleton) under kinetic control and into the tricyclic enedione 5 (patchoulene skeleton) under thermodynamic control is reported.PIERRE DESLONGCHAMPS, JACQUES LAFONTAINE, LUC RUEST et PIERRE SOUCY. Can. J. Chem. 55, 4117 (1977).On rapporte la synthkse de la dicetone cyclopropanique 3 et sa transformation sptcifique en knedione tricyclique 4 (squelette du ctdrkne) sous contr6le cinetique et en knedione tricyclique 5 (squelette du patchoultne) sous contr6le thermodynamique.The sesquiterpenes a-cedrene and a-patchoulene are known to possess the structures 1 (1) and 2 (2) respectively (Scheme I). If both structures are rewritten and represented by formulas 1A and 2A, it is interesting to note that a-cedrene and apatchoulene have rings A and B identical (except for the configuration of the secondary methyl group) and that they differ by the attachment of one of the bonds of ring C. Ring C is attached to C-1 in cedrene and to C-5 in a-patchoulene. Both structures differ also by the position of the methyl group in ring C which is at C-8 in 1A and at C-10 in 2A. This analysis led us to imagine a synthetic.route which could potentially produce both skeletons via a single intermediate. We wish to report the synthesis of the cyclopropane diketone 3, a common intermediate lacking only the methyl group of ring C, and its specific conversion into the tricyclic enediones 4 (cedrene skeleton) or 5 (patchoulene skeleton) respectively. Synthesis of the Cyclopropane Diketone 3The synthetic route chosen to build 3 is described in Scheme 2. Both epimeric diacetate anhydrides 10A (R = H, R' = OAc) and 10B (R = OAc, R' = H) have been obtained pure and were individually transformed into 3. The key steps from 10 are the formation of the tetrasubstituted olefins (10 -+ 12), the Arndt-Eistert homologation of the side chain (12 -+ 16), and the formation of the cyclopropane intermediates (16 + 19) (3) which were then converted into 3 by oxidation of the cyclopropane alcohols 20 and 21. The details of these transforn~ations which occurred in good yield in both epimeric series are described in the Experimental. The pyrolysis of the epimers 11 (A and B) was carried at 200-210°C under nitrogen at atmospheric pressure and this interesting elimination reaction proceeded well in both cases. ' The epimeric mixture (at carbon-2) 9 is known; it is one of the intermediates in the synthesis of a-cedrene carried out by Stork and Clarke (7). In their original synthesis, alkylation of the P-ketoester 6 with benzyl a-bromopropionate gave 7 (X = OCH,C,H,) which was then converted (into the methyl ketone 8) in five operations by the successive transformation of the benzyl ester group into a carboxylic acid (7, X = OH), an acid chloride (7, X = Cl), a diazoketone (7, X = CHN,), an a-chloroketone (7, X = CH,Cl), and a methyl ketone (8).We have repeated this sequence of reactions and have obtained only one epimer (at...

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“…We obtained l a [7] and its 13C-labelled analogues [20] by condensing benzaldehyde with isobutyric acid in the presence of lithium diisopropylamide, following the procedure of Moersch [21]. To test the rearrangement, l a was dissolved in HSO3F/SO2C1F at -1 lo", slowly heated and kept at 0" to + 10" until all NMR.…”

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confidence: 99%

1,2‐Shift of a Carboxyl Group in a Wagner‐Meerwein Rearrangement

Berner

Cox

Dahn

1982

Helvetica Chimica Acta

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On treatment with HS0,F in S02C1F at O", 3-hydroxy-2,2-dimethyl-3-phenylpropionic acid (la) is transformed into 2-phenyl-3-methyl-2-butenoic acid (2a) (isolated yield: 40-44%). Using monolabelled [3-'3C]-la (la*) and doubly labelled [ 1, 3-I3C2]-la (la**), the migration of HOOC (or a mechanistically equivalent group) was proved; a cross experiment established the intramolecular character of the rearrangement. By following the reaction at low temperature in an NMR. spectrometer, the formation of intermediates and side products was demonstrated.In the typical Whitmore 1,2-shift, for instance Wugner-Meerwein, pinacol, benzilic-acid rearrangements, etc., a group is transferred with its bonding electrons to a (more or less completely) electron-deficient centre. Although electron attracting groups would supposedly be disfavoured in such a migration, a significant number of these groups migrate in typical 1,2-shifts to a carbenium-ion-type C-atom, for instance R-CO in Wagner-Meerwein [2], pinacol [3], epoxide [4], and benzilic-acid rearrangements [ 5 ] , ROOC and analogous groups (for a review see [6]) in Wugner-Meerwein [7], pinacol [El, epoxide [9], benzilic-acid [lo], and dienone-phenol rearrangements [ 1 11, R'RNCO-groups in Wagner-Meerwein [ 121 and benzilic-acid rearrangements [ 131, Ar,P (0)-and (RO),P (0)-groups in Wagner-Meerwein [ 141 and epoxide rearrangements [ 151. The (-O,C)-group, less electron attracting, has been shown to migrate in benzilic acid [ 161 and tert.-ketol rearrangements [ 171.In contrast, a migration of a HOOC group has so far not been demonstrated, though it has been supposed to occur in the enzymatic transformation of phenylalanine to tropic acid [ 1 q3).We have demonstrated [20] that EtOOC-and MeOOC-groups are shifted in the Wagner-Meerwein rearrangements of methyl and ethyl 3-hydroxy-2,2-dimethyl-3-phenylpropionate ( l b and lc) into methyl and ethyl 3-methyl-2-phenyl-2-butenoate (2b and 2c) [7]. As a by-product, the free acid 2a had been isolated [20], but it was not established whether hydrolysis had taken place before or after the ') Preliminary communication: [I]. *) 3,Author to whom correspondence should be addressed. The non-enzymatic deamination, however, proceeds via phenyl migration [ 191.

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Synthesis of .beta.-hydroxy acids using .alpha.-lithiated carboxylic acid salts

Abstract: The recent publications by Creger2 have reported the a lithiation of aliphatic carboxylic acids using lithium diisopropylamide in tetrahydrofuran. The a-lithiated acid salts thus formed have been shown to react with alkyl halides and with epoxides.

Cited by 62 publications

References 2 publications

The chemistry of thujone. II. Insect juvenile hormone analogues via acid dianion coupling. The β lactone route

The chemistry of thujone. II. Insect juvenile hormone analogues via acid dianion coupling. The β lactone route

Stereospecific syntheses of the α-patchoulene and α-cedrene skeletons from a common intermediate

1,2‐Shift of a Carboxyl Group in a Wagner‐Meerwein Rearrangement

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