Professor Wei-Min DAI  (PhD, Kyoto, 1990) Professor of Chemistry E-mail:chdai@ust.hk         Tel: (852) 2358-7365; Fax: (852) 2358-1594 ResearcherID: B-6981-2008

(Last updated: 25 February 2012)

Research Interests: Synthetic organic and bioorganic chemistry

Prof. Dai's research focuses on two directions: chirality & catalysis, and synthesis of bioactive molecules including total synthesis of natural products.

Our contribution to chirality & catalysis includes: (1) development of indole-containing chiral molecules from abrine for enantioselective alkylation of aldehydes with diethylzinc; (2) asymmetric Wittig-type olefinations of chiral arsonium ylides with 4-substituted cyclohexanones and N,N-dialkyl 2-formyl-1-naphthamides; (3) remote axial-to-central chirality transfer in SmI2-mediated enantioselective reductive coupling of aldehydes; (4) Pd-catalyzed asymmetric allylic alkylation (AAA), asymmetric Heck reactions, and asymmetric Suzuki–Miyaura reactions using novel atropisomeric amide-derived phosphines (A²phos), C2-symmetric chiral arsines, and P-chiral secondary phosphine oxides; and (5) generation of aromatic amide-derived phosphine (Aphos) ligands via “Self-Assisted Molecular Editing” (SAME) protocol for room temperature Suzuki–Miyaura cross-coupling of unactivated and sterically hindered aryl chlorides under mild basic conditions.

Our accomplishments in synthesis of bioactive molecules cover: (1) total synthesis of amphidinolide X and Y via a ring-closing metathesis (RCM) approach toward formation of the (E)-trisubstituted alkene; (2) diverted total synthesis of amphidinolide T1–T5 and analogues via a RCM–asymmetric dihydroxylation (RCM–AD) sequence; (3) total synthesis of 24-demethylbafilomycins using a novel diester-tethered 1,3-diene–ene RCM; (4) total synthesis and stereochemistry determination of marine butenolides; (5) total synthesis of iriomoteolide-1a diastereomers; (6) total synthesis of mycolactone core via a relay RCM (RRCM) strategy; (7) establishment of an allylic rearrangement strategy for in situ formation of 10-membered ring enediynes with promising DNA cleavage and anticancer activity; (8) development of a number of synthetic methodologies for diversity-oriented synthesis of privileged heterocyclic scaffolds via microwave-assisted multicomponent reactions & post annulation; (9) demonstration of an integrative approach of microwave-assisted solid phase organic synthesis (MASPOS) with encoded split-pool combinatorial synthesis (ESPCS) as illustrated in Cu-mediated heteroannulation for synthesis of indoles and the first introduction of the cat·linker concept for promoting on-resin metal-catalyzed reactions.

Selected Ongoing Projects:

• Total synthesis of macrolides;
• Diversity-oriented synthesis of privileged heterocyclic scaffolds;
• Microwave-assisted organic synthesis (MAOS) & microwave-assisted solid-phase organic synthesis (MASPOS);
• Development of novel atropisomeric amide-derived phosphines (A²phos) for enantioselective catalysis;
• Design and synthesis of enantiomeric non-biaryl atropisomers for asymmetric synthesis.

Selected Journal Publications:    [see more entries]

Chirality & Catalysis:

• Determination of absolute configuration of 2-methyl-1-(o-tolyl)naphthalene and the related axially chiral biaryls: Tetrahedron 2011, 67, 9072–9079. [DOI: 10.1016/j.tet.2011.09.107] [new]
• In(OTf)3-catalyzed highly chemo- and regioselective head-to-tail heterodimerization of vinylarenes with 1,1-diarylethenes: Chem. Eur. J. 2011, 17, 8290–8293. [DOI: 10.1002/chem.201101190]
• Generation of an aromatic amide-derived phosphane (Aphos) library by self-assisted molecular editing and applications of Aphos in room-temperature Suzuki-Miyaura reactions: Chem. Eur. J. 2008, 14, 5538–5554. [DOI: 10.1002/chem.200800318]
• Efficient remote axial-to-central chirality transfer in enantioselective SmI2-mediated reductive coupling of aldehydes with crotonates of atropisomeric 1-naphthamides: J. Org. Chem. 2006, 71, 2445–2455. [DOI: 10.1021/jo0526486]
• A novel class of nonbiaryl atropisomeric P,O-ligands for palladium-catalyzed asymmetric allylic alkylation: Org. Lett. 2002, 4, 1615–1618. [DOI: 10.1021/ol0258233]

Total Synthesis:

• Concise diverted total synthesis of amphidinolide T1 and T4 from a (12E)-cycloalkene by selective functionalized of the C12–C13 double bond: Synlett 2011, 3036–3040. [DOI: 10.1055/s-0031-1289903] [new]
• Synthesis of two diastereoisomers of iriomoteolide-1a via a tunable four-module coupling approach using ring-closing metathesis as the key step: Synlett 2011, 1774–1778. [DOI: 10.1055/s-0030-1260822]
• Total synthesis of amphidinolide T3 using ring-closing metathesis and asymmetric dihydroxylation strategy: Synlett 2011, 895–898 [DOI: 10.1055/s-0030-1259706] [special issue dedicated to Professors Xiyan Lu and Li-Xin Dai].
• A concise total synthesis amphidinolide T2: Chem. Eur. J. 2010, 16, 11530–11534. [DOI: 10.1002/chem.201001794]
• Synthesis of the C7–C23 fragment related to iriomoteolide-1a via B-alkyl Suzuki–Miyaura cross-coupling and indium-mediated aldehyde allylation: Synlett 2010, 2184–2188. [DOI: 10.1055/s-0030-1258507]
• Influence of appended groups on formation of 16-membered macrolactone core related to the plecomacrolides via diene–ene ring-closing metathesis: Synlett 2009, 2361–2365. [DOI: 10.1055/s-0029-1217720]
• Total synthesis of amphidinolide X and its 12Z-isomer by formation of the C12–C13 trisubstituted double bond via ring-closing metathesis: Synlett 2008, 1737–1741. [DOI: 10.1055/s-2008-1077885]
• Total synthesis of amphidinolide Y by formation of trisubstituted (E)-double bond via ring-closing metathesis of densely functionalized alkenes: Org. Lett. 2007, 9, 2585-2588. [DOI: 10.1021/ol0710360]
• Synthesis of C13–C25 fragment of 24-demethylbafilomycin C1 via diastereoselective aldol reactions of a ketone boron enolate as the key step: J. Org. Chem. 2007, 72, 4953–4960. [DOI: 10.1021/jo070624o]

Microwave-Assisted & Diversity-Oriented Organic Synthesis:

• Tandem Wittig–intramolecular Diels–Alder cycloaddition of ester-tethered 1,3,9-decatrienes under microwave heating: Tetrahedron 2011, 67, 179–192. [DOI: 10.1016/j.tet.2010.10.088] [new]
• Synthesis of Anti-Microtubule N-(2-Arylindol-7-yl)benzenesulfonamide Derivatives and Their Antitumor Mechanisms: ChemMedChem, 2010, 5, 1489–1497. [DOI: 10.1002/cmdc.201000228]
• Synthesis of N-arylisoindolin-1-ones via Pd-catalyzed intramolecular decarbonylative coupling of N-(2-bromobenzyl)oxanilic acid phenyl esters: Synlett 2010, 1075–1080. [DOI: 10.1055/s-0029-1219580]
• Stereoselectivity of intramolecular Diels–Alder reaction of hydroxamate-tethered 1,3,9-decatrienes under thermal and microwave heating: Synlett 2009, 2862–2866. [DOI: 10.1055/s-0029-1217966]
• Assembly of 1,3-dihydro-2H-3-benzazepin-2-one conjugates via Ugi four-component reaction and palladium-catalyzed hydroamidation: Synlett 2009, 1162–1166. [DOI: 10.1055/s-0028-1088115]
• Lewis acid-catalyzed formation of Ugi four-component reaction product from Passerini three-component reaction system without an added amine: Tetrahedron 2007, 63, 12866–12876. [DOI: 10.1016/j.tet.2007.10.050]
• Diversity-oriented synthesis and solid-phase organic synthesis under controlled microwave heating: Comb. Chem. High Throughput Screening 2007, 10, 837–856. [DOI: 10.2174/138620707783220338]
• Microwave-assisted one-pot U-4CR and intramolecular O-alkylation toward heterocyclic scaffolds: Tetrahedron 2006, 62, 6774–6781. [DOI: 10.1016/j.tet.2006.05.001]

Microwave-Assisted Solid-Phase Organic Synthesis (MASPOS):

• An engineered linker capable of promoting on-resin reactions for microwave-assisted solid-phase organic synthesis: Angew. Chem. Int. Ed. 2006, 45, 7255–7258. [DOI: 10.1002/anie.200602523]
• Microwave-assisted solid-phase organic synthesis (MASPOS) as a key step for an indole library construction: Org. Lett. 2003, 5, 2919–2922. [DOI: 10.1021/ol0350543]

Designed Enediyne Prodrugs:

• Natural product inspired design of enediyne prodrugs via rearrangement of an allylic double bond: Curr. Med. Chem. 2003, 10, 2265–2283. [DOI: 10.2174/0929867033456756]
• DNA cleavage potency, cytotoxicity, and mechanism of action of a novel class of enediyne prodrugs: J. Med. Chem. 2002, 45, 758–761. [DOI: 10.1021/jm015588e]
• Synthesis of cis-enediynes from 1,5-diynes by rearrangement of an allylic double bond  Angew. Chem. Int. Ed. Engl. 1996, 35, 779–781. [DOI: 10.1002/anie.199607791]

Recent Conference Presentations:    [see more entries]

• Invited Talk. "Total synthesis of mycolactone core via relay ring-closing metathesis", 2011 Chinese Medicinal Chemistry Symposium & China-UK Symposium on Medicinal Chemistry, Guangzhou, China, 17-20 November 2011. [new] 
• Invited Talk. "Diverted total synthesis of amphidinolide T1, T3, and T4", The 5th International Conference on Multi-Component Reactions and Related Chemistry (MCR2011), Hangzhou, China, 14–17 November 2011.
• Invited Talk. "Microwave-assisted post-Ugi annulations for creation of heterocycle skeleton diversity", Diversity-Oriented Synthesis (#32), Pacifichem 2010, Honolulu, Hawaii, USA, 19 December, 2010.
• Invited Talk. "Total synthesis of amphidinolide T2 and butenolides", 12th International Symposium on Natural Product Chemistry (ISNPC-12), Karachi, Pakistan, 22–25 November, 2010.
• Invited Talk. "Total synthesis of anticancer plecomacrolide, 24-demethylbafilomycin C1 via ring-closing metathesis of the grafted substrates", Asian Federation for Pharmaceutical Sciences 2009 (AFPS2009), Fukuoka, Japan, 15–18 October, 2009.
• Invited Talk. "Building molecular shape diversity via post-Ugi annulations", IV International Conference on Multicomponent Reactions and Related Chemistry (MCR2009), Ekaterinburg, Russia, 24–28 May 2009.

Recent PhD Theses:    [see more entries]

• Jing DAI: Metal Complex-/Lewis Acid-Catalyzed C-C Bond Forming Reactions for Synthesis of Functionalized Alkenes, 2011, ZJU, China. [new]
• Yuanxin LIU: Preparation of a Cinnamide Library and Total Synthesis of Stereoisomers of Marine Macrolide Iriomoteolide-1a, 2011, ZJU, China.

since 21 May 2001