Review Finite Element Modeling - University of Massachusetts Lowell
Massachusetts Institute of Technology, Department of … 2003, 125, 11514-11515 3. Elizabeth A....
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1 1. Johann Chan and Timothy F. Jamison; JACS, 2004, ASAP 2. Johann Chan and Timothy F. Jamison; JACS, 2003, 125, 11514-11515 3. Elizabeth A. Colby and Tomothy F. Jamison; JOC, 2003, 68, 156-166 Massachusetts Institute of Technology, Department of Chemistry
Transcript of Massachusetts Institute of Technology, Department of … 2003, 125, 11514-11515 3. Elizabeth A....
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1. Johann Chan and Timothy F. Jamison;JACS, 2004, ASAP
2. Johann Chan and Timothy F. Jamison;JACS, 2003, 125, 11514-11515
3. Elizabeth A. Colby and Tomothy F.Jamison; JOC, 2003, 68, 156-166
Massachusetts Institute of Technology, Department of Chemistry
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History of terpestacin 1 and siccanol 2:
• 1993 Isolation of 1 (Arthrinium sp.) Oka [α]D= +26o (CHCl3, 22 oC)
• 1998 Enantiospecific synthesis of 1 Tatsuta [α]D= +27o (CHCl3)
• 2001 Isolation of “enantiomer of 1” (Ulocladium sp.) Gräfe [α]D= -16.5o (CDCl3, 25 oC)
[α]D= -21.5o (MeOH, 25 oC)
• 2002 Enantioselective syntheses of 1 & 3 Myers [α]D= -17o (CHCl3, 28 oC)
[α]D= -18o (MeOH, 25 oC)
Gräfe’s discovery is 1 itself
• 2002 Isolation of “siccanol 2” (Bipolaris sorokiniana) Miyagawa
• 2003 Enantioselective syntheses of 1 & 2 Jamison siccanol 2 is actually terpestacin 1
Bioactivities ofterpestacin 1• Inhibits the formation ofsyncytia, giant-multinucleated cell relatedto HIV infection
• Inhibits angiogenesis
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4Johann Chan and Timothy F. Jamison; JACS, 2004, ASAP
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Elizabeth A. Colby and Tomothy F. Jamison; JOC, 2003, 68, 156-166
Ni-catalyzed Asymmetric Reductive Coupling
6Elizabeth A. Colby and Tomothy F. Jamison; JOC, 2003, 68, 156-166
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Proposed Mechanism
Elizabeth A. Colby and Tomothy F. Jamison; JOC, 2003, 68, 156-166
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Macrocyclization of Model Substrate 12
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Synthesis of the cis-fused 5,5-ring System
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Fs =
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Other Attempts on Intramolecular Cyclization
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R1 R2 H R3
O
+ R1
R2
OH
R3
Ni(COD)2 (10 mol%)Bu3P (20 mol%)Et3B (200 mol%)
Toluene, rt, 18h
R1 = Ph, R2 = SiMe3, R3 = n-Hept 89% (> 98:2)
R1 = n-Bu, R2 = SiMe3, R3 = n-Hept 58% (> 98:2)
Weisheng Huang, Johann Chan and Timothy F. Jamison, OL, 2000, 4221-4223
Intermolecular Coupling of Alkynylsilanes
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Intramolecular Cyclization of an Alkynylsilane
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Possible Reason for the Failure
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Intermolecular Strategy: Synthesis of Fragment 9 and 10
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Intermolecular Ni-catalyzed Reductive Coupling
Diastereoselectivity Regioselectivity overall yield(42a+42c/42b+42d) (42a+42b/42c+42d)
PBu3 1 : 1 1.5 : 141e 2 : 1 2.6 : 1 85%
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18h
H
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