Concise synthesis of functionalized benzocyclobutenones

Chen, Peng‐Hao; Savage, Nikolas A.; Dong, Guangbin

doi:10.1016/j.tet.2014.03.080

Cited by 30 publications

(21 citation statements)

References 81 publications

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“…Hence, this three-step route offers a rapid and high-yielding entry to substrate 5 for the subsequent C–C activation, which otherwise would take around 6 steps using the prior preparation routes. 3,17…”

Section: Resultsmentioning

confidence: 99%

Concise Synthesis of (−)-Cycloclavine and (−)-5-epi-Cycloclavine via Asymmetric C–C Activation

2018

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To illustrate the synthetic significance of C-C activation methods, here we describe an efficient strategy for the enantioselective total syntheses of (-)-cycloclavine and (-)-5- epi-cycloclavine, which is enabled by an asymmetric Rh-catalyzed "cut-and-sew" transformation between benzocyclobutenones and olefins. Despite the compact structure of cycloclavine with five-fused rings, the total synthesis was accomplished in 10 steps with a 30% overall yield. Key features of the synthesis include (1) a Pd-catalyzed tandem C-N bond coupling/allylic alkylation sequence to construct the nitrogen-tethered benzocyclobutenone, (2) a highly enantioselective Rh-catalyzed carboacylation of alkenes to forge the indoline-fused tricyclic structure, and (3) a diastereoselective cyclopropanation for preparing the tetrasubstituted cyclopropane ring. Notably, an improved catalytic condition has been developed for the nitrogen-tethered cut-and-sew transformation, which uses a low catalyst loading and allows for a broad substrate scope with high enantioselectivity (94-99% e.e.). The C-C activation-based strategy employed here is anticipated to have further implications for syntheses of other natural products that contain complex fused or bridged rings.

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Section: Resultsmentioning

confidence: 99%

Concise Synthesis of (−)-Cycloclavine and (−)-5-epi-Cycloclavine via Asymmetric C–C Activation

2018

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“…To explore the feasibility of the key enantioselective “cut‐and‐sew” step, a simplified model substrate ( 7 a ) was prepared from commercially available aryl bromide 11 through a sequence of benzocyclobutenone synthesis using our previously developed protocol, [13a] followed by the Mitsunobu coupling with a known alcohol ( 8 a ) [13b] (Scheme 4). Notably, phenol 9 can be prepared on decagram scales in 70 % overall yield with only one column chromatography purification needed.…”

Section: Resultsmentioning

confidence: 99%

Deconstructive Asymmetric Total Synthesis of Morphine‐Family Alkaloid (−)‐Thebainone A

2021

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Herein, we describe the development of ad econstructive strategy for the first asymmetric synthesis of (À)thebainone A, capitalizing on an enantioselective CÀCb ond activation and aC ÀOb ond cleavage reaction. The rhodiumcatalyzeda symmetric "cut-and-sew" transformation between sterically hindered trisubstituted alkenes and benzocyclobutenones allowed efficient construction of the fused A/B/C rings and the quaternary center of the natural product. The newly optimizedconditions show broad substrate scope and excellent enantioselectivity (up to 99.5:0.5 er). Taking advantage of boron-mediated ether bond cleavage,w ec ompleted the synthesis of the morphine alkaloid (À)-thebainone Ab yt wo complementary routes. Figure 1. Morphine and related alkaloids.

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“…As shown in Scheme 3a , the synthesis of haouamine A ( 1 ) commenced with the preparation of amino-alcohol 7 . Inspired by the protocol originally developed by Wang and co-workers, 6 rhodium-catalyzed diazo-insertion reaction engaging benzocyclobutanol 4 ( ref. 8 ) and diazoester 5 ( ref.…”

Section: Resultsmentioning

confidence: 99%