Synthesis of the Polycyclopropane Antibiotic FR-900848 via the Horeau Gambit

Falck, John R.; Mekonnen, Belew; Yu, Jurong; Lai, Jing Yu

doi:10.1021/ja961093g

Cited by 78 publications

(35 citation statements)

References 16 publications

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“…[7][8][9][10] The total synthesis of FR-900848 1 [11,12] and U-106305 2 [12,13] was achieved in 1996 by Barrett et al, and the key step for the stereoselective assembly of the quatercyclopropane moiety was the enantioselective Simmons-Smith-type cyclopropanation of 2-butene-1,4-diol as developed by Charette et al [14] The higher acyclic and even cyclic syn-all-trans-oligocyclopropyl-1,n-dimethanol derivatives have been prepared not only as precursors to the natural products 1 and 2 but also out of interest in their conformational behavior. [15] Having gained some experience with the conformational analysis of bicyclopropyl early on, [16,17] we were intrigued by the conformational features of the quater-and quinquecyclopropane units in 1 and 2.…”

Section: Introductionmentioning

confidence: 99%

Stereoselective Preparation of Six Diastereomeric Quatercyclopropanes from Bicyclopropylidene and Some Derivatives

Seebach

Kozhushkov

Schill

et al. 2006

Chemistry A European J

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Diastereomeric meso‐ and d,l‐bis(bicyclopropylidenyl) (5) were obtained upon oxidation with oxygen of a higher‐order cuprate generated from lithiobicyclopropylidene (4) in 50 and 31 % yield, respectively. Their perdeuterated analogues meso‐[D14]‐ and d,l‐[D14]‐5 were obtained along the same route from perdeuterated bicyclopropylidene [D8]‐3 (synthesized in six steps in 7.4 % overall yield from [D8]‐THF) in 20.5 % yield each. Dehalogenative coupling of 1,1‐dibromo‐2‐cyclopropylcyclopropane (6) gave a mixture of all possible stereoisomers of 1,5‐dicyclopropylbicyclopropylidene 16 in 69 % yield, from which (Z)‐cis‐16 was separated by preparative gas chromatography (26 % yield). The crystal structure of meso‐5 looks like a superposition of the crystal structures of two outer bicyclopropylidene units (3) and one inner s‐trans‐bicyclopropyl unit, whereas the two outer cyclopropyl moieties adopt a gauche orientation with respect to the cyclopropane rings at the inner bicyclopropylidene units in (Z)‐cis‐16. Birch reduction with lithium in liquid ammonia of meso‐5 and d,l‐5 gave two pairs of diastereomeric quatercyclopropanes trans,trans‐(R*,S*,R*, S*)‐17/cis,trans‐(R*,S*,R*,R*)‐18 and trans,trans‐(R*,S*,S*,R*)‐19/cis,trans‐(R*,S*,S*,S*)‐20 in 97 and 76 % yield, respectively, in a ratio 9:1 for every pair. The latter diastereomer was also obtained as the sole product by Birch reduction of (Z)‐cis‐16 in 96 % yield. Under the same conditions, tetradecadeuterio analogues trans,trans‐[D14]‐(R*,S*,R*,S*)‐17/cis,trans‐[D14]‐(R*, S*,R*,R*)‐18 (8:1) and trans,trans‐[D14]‐(R*,S*,S*,R*)‐19/cis,trans‐[D14]‐(R*,S*,S*,S*)‐20 (12:1) were prepared from meso‐[D14]‐5 and d,l‐[D14]‐5 in 37 and 63 % yield, respectively. Reduction of meso‐5 with diimine gave the cis,cis‐quatercyclopropane (S*,S*,R*,R*)‐21 as the main product (58 % yield) along with the cis,trans‐diastereomer (S*,S*,R*,S*)‐18 (29 % yield). Thus, five of the six possible diastereomeric quatercyclopropanes were obtained from meso‐5, d,l‐5, and (Z)‐cis‐16. The X‐ray crystal structure analyses of trans,trans‐(R*,S*,R*,S*)‐17 and cis,cis‐(S*,S*,R*,R*)‐21 revealed for the both an unusual conformation in which the central bicyclopropyl unit adopts an s‐trans‐(antiperiplanar) orientation with ϕ=180.0°, and the two terminal bicyclopropyl moieties adopt a synclinal conformation with ϕ=49.8 and 72.0°, respectively. In solution the vicinal coupling constants 〈3JH,H〉 in trans,trans‐(R*,S*,R*,S*)‐[D14]‐17, trans,trans‐(R*,S*,S*,R*)‐[D14]‐19, trans,cis‐(R*,S*,R*,R*)‐[D14]‐18 and trans,cis‐(R*,S*,S*,S*)‐[D14]‐20 were found to be 4.1, 4.7, 5.9 and 5.9 Hz, respectively. This indicates a predominance of the all‐gauche conformer in (R*,S*,R*,S*)‐17 and a decreasing fraction of it in this sequence of the other diastereomers.

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Section: Introductionmentioning

confidence: 99%

Stereoselective Preparation of Six Diastereomeric Quatercyclopropanes from Bicyclopropylidene and Some Derivatives

Seebach

Kozhushkov

Schill

et al. 2006

Chemistry A European J

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“…Next, we focused on the thermal decarboxylation of the corresponding Barton thiohydroxamic ester [24] in the presence of iodoform, a sequence that was successfully applied (in the presence of bromoform) by Falck et al in their synthesis of the oligocyclopropane antibi- otic FR-900848. [25,26] We observed low yields for the formation of iodide 6 when we introduced the ester via the acid chloride (33%). Direct esterification using DCC (dicyclohexylcarbodiimide) proved unsatisfactory as well.…”

Section: Resultsmentioning

confidence: 94%

Enantiomerically Pure Cyclopropane Building Blocks: Synthesis and Transformations of 2‐Iodocyclopropylboronic Esters

Hohn¹,

Pietruszka²

2004

Adv Synth Catal

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Dedicated to Joe P. Richmond on the occasion of his 60 th birthday.Abstract: Enantiomerically pure 2-iodocyclopropylboronic esters 6 and 8 have been synthesized from the readily available allylic alcohol 2 via an oxidation-radical decarboxylation sequence. These unique building blocks have been demonstrated to be versatile intermediates for a consecutive Suzuki-coupling with aryl-, heteroaryl-, alkenyl-, and cyclopropylboron derivatives (1 example each).

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“…[22] This transformation had previously proved to be applicable to cyclopropanecarboxylic acids. [23] Thus, under the published conditions, the acid (1S,3R,4S)-18 [prepared analogously to (1R,3S,4S)-18 in 90 % yield, see Exp. Sect.]…”

Section: Preparation Of the New Ligandsmentioning

confidence: 98%

A Novel Type of Chiral Triangulane‐Based Diphosphane Ligands for Transition Metals

et al. 2012

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A new original strategy for the synthesis of axially and helically chiral bidentate diphosphane ligands featuring a rigid triangulanyl backbone has been elaborated and executed for several representative enantiomerically pure ligands. Thus,(1R,3S,4S)‐1,4‐bis[(diphenylphosphanyl)methyl]spiro[2.2]pentane [(1R,3S,4S)‐24·(BH3)2], [(1R,3R,4S)‐4‐(diphenylphosphanyl)methylspiro[2.2]pentan‐1‐yl]diphenylphosphane [(1R,3R,4S)‐27·(BH3)2], [(1R,3R,4S,5R)‐5‐(diphenylphosphanyl)methyldispiro[2.0.2.1]heptan‐1‐yl]diphenylphosphane [(1R,3R,4S,5R)‐30·(BH3)2], (1S,3S,4S)‐1,4‐bis(diphenylphosphanyl)spiropentane [(1R,3S,4S)‐35·(BH3)2], (1S,3S,4S)‐1,4‐bis(diphenylphosphanyl)spiropentane [(1S,3S,4S)‐35·(BH3)2], (1S,3S,4S)‐1,4‐bis(diphenylphosphanyl)spiropentane [(1R,3R,4S)‐35·(BH3)2], and (1R,3R,4R,5R)‐1,5‐bis(diphenylphosphanyl)dispiro[2.0.2.1]heptane [(1R,3R,4R,5R)‐36·(BH3)2] with a spiropentyl and a dispiro[2.0.2.1]heptyl moiety, respectively, have been prepared as bishydroborane complexes applying repetitively the same set of standard synthetic operations, starting from [(1S,3R)‐4‐methylenespiropent‐1‐yl]methyl acetate [(1S,3R)‐7], (4,4‐dibromospiropent‐1‐yl)methanols [(1S,3R)‐8 and (1R,3S)‐8] and (dibromodispiro[2.0.2.1]heptyl)methanols (1R,3S,4R)‐9, (1S,3R,4S)‐9 and (1S,3R,4R)‐9 in 4–7 steps. The relative configurations of all important intermediates as well as the absolute configurations of the key intermediates and most final products were established by X‐ray crystal structure analyses.

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Synthesis of the Polycyclopropane Antibiotic FR-900848 via the Horeau Gambit

Cited by 78 publications

References 16 publications

Stereoselective Preparation of Six Diastereomeric Quatercyclopropanes from Bicyclopropylidene and Some Derivatives

Stereoselective Preparation of Six Diastereomeric Quatercyclopropanes from Bicyclopropylidene and Some Derivatives

Enantiomerically Pure Cyclopropane Building Blocks: Synthesis and Transformations of 2‐Iodocyclopropylboronic Esters

A Novel Type of Chiral Triangulane‐Based Diphosphane Ligands for Transition Metals

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