Enantiodivergent syntheses of cycloheptenone intermediates for guaiane sesquiterpenes

Faria, Mary Leiva de; Magalhães, Ruy de A.; Silva, Fernando C.; Matias, Luiz Gonzaga de Oliveira; Ceschi, Marco Antonio; Brocksom, Ursula; Brocksom, Timothy J.

doi:10.1016/s0957-4166(00)00387-6

Cited by 30 publications

(19 citation statements)

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“…The enantiodivergent strategy we have developed 3 requires a double bond in the para-menthane structure at the C-1 to C-2 centers for the (R)-cycloheptenone enantiomer or the C-1 to C-6 centers for the (S)-enantiomer (Scheme 3). …”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Our interest in their synthesis has led us to develop methods for the transformation of para-menthane monoterpenes into single isomer cycloheptenones, [2][3][4] and then by pent-annelation 5,6 into the required complete carbon skeleton. Scheme 1 outlines our synthetic strategy which involves two quite different routes for the ring expansion, by cyclopropanation and central sigma bond cleavage 2,3 or nucleophilic addition and rearrangement. 4 The intermediate cycloheptenone can then by pent-annelated by more classical ionic reactions (allylation, Wacker oxidation and intramolecular aldol reaction) 5 or by the ring closing metathesis 6 of a suitable neighboring allyl-vinyl derivative.…”

Section: Introductionmentioning

confidence: 99%

“…Determination of the optical activity allowed comparison with samples prepared earlier in our laboratory 3 …”

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confidence: 99%

“…The weak base catalyzed enolization leads to the thermodynamically preferred enolate which is captured by both trimethylsilyl chloride and triethylsilyl chloride, leading to enolethers 4a and 4b in excellent overall yields from carvone (1). 3 The key step of chemoselective cyclopropanation of 4 to produce the substituted nor-carane 5 was executed by the Furukawa modification 8 of the Simmons-Smith reaction, 9 using methylene iodide in the presence of diethylzinc. This reaction was found to be very capricious with respect to reproducibility and highly influenced by the two reagents.…”

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The enantioselective synthesis of (R)-(+)-6-isopropenyl-3-methyl-2-cycloheptenone

Brocksom¹,

Brocksom²,

Barbosa³

2006

J. Braz. Chem. Soc.

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final, um quiron para a síntese de produtos naturais sesquiterpênicos do tipo guaiano, foi obtido em cinco etapas com 38% de rendimento global. (R)-(+)-6-isopropenyl-3-methyl-2-cycloheptenone is synthesized from (R)-(-)-carvone byreduction and trialkylsilyl-enolether formation, cyclopropanation with methylene iodide and diethylzinc, followed by a Saegusa type oxidation with ferric chloride and finally dehydrochlorination with base. The title compound is obtained in five steps and 38% overall yield, being a useful chiron for guaiane sesquiterpene natural products.Keywords: cycloheptenone, carvone, ring expansion, perhydroazulene, enantioselectivity IntroductionThe total synthesis of guaiane sesquiterpenes 1 is of current interest due to innumerous examples of these natural products with relevant biological activities, and the challenge of the perhydroazulene carbon skeleton containing two methyl and an isopropyl groups. Our interest in their synthesis has led us to develop methods for the transformation of para-menthane monoterpenes into single isomer cycloheptenones, 2-4 and then by pent-annelation 5,6 into the required complete carbon skeleton. Scheme 1 outlines our synthetic strategy which involves two quite different routes for the ring expansion, by cyclopropanation and central sigma bond cleavage 2,3 or nucleophilic addition and rearrangement. 4 The intermediate cycloheptenone can then by pent-annelated by more classical ionic reactions (allylation, Wacker oxidation and intramolecular aldol reaction) 5 or by the ring closing metathesis 6 of a suitable neighboring allyl-vinyl derivative.Thus far we have developed several distinct methodologies for the ring expansion of different para-menthane monoterpenes, and in this paper we would like to describe a new route which transforms readily available (R)-(-)-carvone (1) into the desired (R)-(+)-6-isopropenyl-3-methyl-2-cycloheptenone (2) in five steps and 38% overall yield (Scheme 2), with complete regioselectivity and retention of stereochemical integrity. Results and DiscussionThe enantiodivergent strategy we have developed 3 requires a double bond in the para-menthane structure at the C-1 to C-2 centers for the (R)-cycloheptenone enantiomer or the C-1 to C-6 centers for the (S)-enantiomer (Scheme 3). 793The Enantioselective Synthesis of (R)-(+)-6-Isopropenyl-3-Methyl-2-Cycloheptenone Vol. 17, No. 4, 2006 Herein we describe an enantio-and regioselective route to the (R)-enantiomer of 2 by regioselective formation of the trialkylsilyl-enolether 4 of dihydrocarvone (3) followed by chemoselective cyclopropanation and oxidative cleavage of the common sigma bond. Elimination of HCl with base completes the synthesis of 2 (Scheme 4).A similar strategy was used by Marques et al. 7 in the synthesis of the sesquiterpene africanol, for the ring expansion of 2,5,5-trimethyl-cyclohexanone.The reduction of the conjugated double bond of (R)-(-)-carvone (1) can be readily effected with zinc dust in alkaline methanol/water as we have developed 3 in our laboratory, as a sim...

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Determination of the optical activity allowed comparison with samples prepared earlier in our laboratory 3 …”

mentioning

confidence: 99%

mentioning

confidence: 99%

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The enantioselective synthesis of (R)-(+)-6-isopropenyl-3-methyl-2-cycloheptenone

Brocksom¹,

Brocksom²,

Barbosa³

2006

J. Braz. Chem. Soc.

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Asymmetric Cyclopropanation

2017

Asymmetric Synthesis of Three‐Membered Rings

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Studies on the Synthesis of Schisandraceae Natural Products: Exploring a Cyclopropylcarbinol Ring Expansion Strategy

Fischer

Theodorakis

2007

Eur J Org Chem

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Acid mediated cyclopropylcarbinol ring expansion has been shown to be a viable method for the construction of the AB ring framework of lancifodilactone F and related terpenoids of the Schisandraceae family of natural products. We found that this rearrangement proceeds with good stereochemical control based on inversion of the C10 cyclopropyl center. Our studies indicate that the cis‐decalin motif of 31 could be used as a key synthetic precursor of certain Schisandraceae metabolites.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

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Enantiodivergent syntheses of cycloheptenone intermediates for guaiane sesquiterpenes

Cited by 30 publications

References 22 publications

The enantioselective synthesis of (R)-(+)-6-isopropenyl-3-methyl-2-cycloheptenone

The enantioselective synthesis of (R)-(+)-6-isopropenyl-3-methyl-2-cycloheptenone

Asymmetric Cyclopropanation

Studies on the Synthesis of Schisandraceae Natural Products: Exploring a Cyclopropylcarbinol Ring Expansion Strategy

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