Literature Meeting - Charette Group – Marc K. Janes – December 6 th 2004 ACTIVATIONS BY HYDROGEN BONDING – SUCCESS STORIES Born Rajkot, India, University of Connecticut, B.S., University of Pennsylvania, Ph.D., Columbia University, Postdoctoral Fellow, The Ohio State University Professor The University of Chicago, Professor, : Postdoctoral Fellow, MIT Professor K. Barry Sharpless : University of California, Ph.D. Professor Robert G. Bergman : New York University B.S. Professor Yorke E. Rhodes Eric N. Jacobsen Viresh H. Rawal

Literature Meeting - Charette Group – Marc K. Janes – December 6 th 2004 ACTIVATIONS BY HYDROGEN BONDING – OUTLINE 1)The Hydrogen Bond 2)Acid catalysis (concepts) 3)Recent examples in organic chemistry 1)Seminal work (from hine to jacobsen) 2)Diels-Alders (Rawal) 3)Other reactions

Steiner, ACIEE 2002, 48 (review) THE HYDROGEN BOND – DEFINITIONS Pimentel and McClellan: ‘’…a hydrogen bond exists 1)There is evidence of a bond 2)There is evidence that this bond sterically involves a hydrogen atom already bonded to another atom…’’. Drawback: May include van der Waals interactions and agostic interactions (3 center 2 electrons). Proposed definition: An X-H A interaction is called a ‘’hydrogen bond’’: 1.It constitutes a local bond. 2.X-H acts as proton donor to A. E tot = E electrostatic + E polarization + E charge transfer + E despersion + E exchange repulsion

Steiner, ACIEE 2002, 48 (review) THE HYDROGEN BOND – A REVIEW

Steiner, ACIEE 2002, 48 (review) THE HYDROGEN BOND – ENERGY IN GAS PHASE TO BE TAKEN WITH CAUTION NO MEDIUM EFFECT IN GAS PHASE IDEAL GEOMETRY WAS USED IN THE CALCULATIONS H-BONDS OFTEN FORM NETWORKS AND ARE NOT ADDITIVE (CANNOT SPLIT ENERGY ON EACH BOND)

Steiner, ACIEE 2002, 48 (review) THE HYDROGEN BOND – A REVIEW

Steiner, ACIEE 2002, 48 (review) THE HYDROGEN BOND – A REVIEW

TYPES OF BRONSTED ACID CATALYSIS HYDROGEN BONDS ARE INVOLVED IN THE ACTIVATION OF THE SUBSTRATE AND THESE HYDROGENS ARE TRANSFERRED ONLY AT THE TRANSITION STATE

THE BRONSTED CATALYSIS LAW Rate depends on [H 3 O + ] : SAC Rate depends on [HA] : GAC

Pihko, ACIEE 2004, 2062 (highlight) MODES OF CARBONYL ACTIVATION BY COORDINATION

Etter, JACS 1988, 5896; Acc. Chem. Res. 1990, 120. Kelly, TL 1990, EXAMPLES OF INTERACTIONS

Curran, JOC 1994, 3259; TL 1995, Radical allylation EXAMPLES OF INTERACTIONS

Jacobsen, JACS 1998, 1401 JACOBSEN (SIGMAN) – STRECKER (must find a project that works…)

Jacobsen, JACS 1998, 1401; ACIEE 2000, 1279 JACOBSEN (SIGMAN) - STRECKER

Jacobsen, ACIEE 2000, 1279 JACOBSEN (SIGMAN) - STRECKER

Jacobsen, ACIEE 2000, 1279 JACOBSEN (SIGMAN) – STRECKER (MACHOISM)

Jacobsen, ACIEE 2000, 1279 JACOBSEN (SIGMAN) - STRECKER

Jacobsen, OL 2000, 867 JACOBSEN – STRECKER ON KETOIMINES 1c

Jacobsen, JACS 2002, JACOBSEN – REACTION KINETICS Model reaction Previously optimal catalyst

Jacobsen, JACS 2002, JACOBSEN – KINETIC STUDY OF UREA CATALYST INTERCEPT IS 1/v MAX Indicating that There is a V MAX

Jacobsen, JACS 2002, JACOBSEN – REACTION KINETICS CONCLUSIONS Model reaction Previously optimal catalyst - 1 st order in HCN and Catalyst -Saturation kinetics of imine (proven by Lineweaver Burk) - Obeys Michaelis-Meten kinetics (steady state kinetics) Implicates the reversible formation of an IMINE – CATALYST COMPLEX

Jacobsen, JACS 2002, JACOBSEN – PROBES INTO BINDING (where are the interactions?)

Jacobsen, JACS 2002, 10012; SEE MARCELO IN JANUARY JACOBSEN – BINDING STUDY OF UREA CATALYST

Jacobsen, JACS 2002, 10012; SEE MARCELO IN JANUARY JACOBSEN – BINDING STUDY OF UREA CATALYST

Jacobsen, JACS 2002, JACOBSEN – BINDING STUDY OF UREA CATALYST 3

Jacobsen, JACS 2002, JACOBSEN – IMINE GEOMETRY IN SOLUTION AND REACTIVE FORM Only the Z Interacts! Good reaction with fixed Z imine (ACIEE)Unreactive Fixed E imine ADDITION OF CATALYST

Jacobsen, JACS 2002, 10012; SEE CLAUDE ANY TIME JACOBSEN – OUR FRIEND THE COMPUTER Solvent has little effect on solution phase structure (justification for gas phase approximation)

Jacobsen, JACS 2002, JACOBSEN – BINDING STUDY OF UREA CATALYST Adopts a well defined secondary structure in solution (1) The large group on the imine carbon is directed away from the catalyst and into solvent (Figure 1B); this serves to explain why 1 catalyzes hydrocyanation of most aldimines with high ee, regardless of the steric and electronic properties of the substrate. (2) The small group (H for aldimines, Me for methylketoimines) is aimed directly into the catalyst; ketoimines bearing larger substituents are poor substrates for the reaction,2c presumably because they cannot be accommodated within the optimal geometry. (3) The N-substituent is also directed away from the catalyst. However, its size is restricted as a result of the requirement to access the Z-isomer of the imine. (4) On the basis of the observed sense of stereoinduction, addition of HCN takes place over the diaminocyclohexane portion of the catalyst (i.e., from the right-hand side in Figure 1C) and away from the amino acid/amide portion. The last hypothesis leads to the prediction that increasing the steric properties of the amino acid/amide portion of the catalyst should lead to higher enantioselectivity in the hydrocyanation reactions.

Jacobsen, JACS 2002, JACOBSEN – UREA RATIONAL DESIGN

Jacobsen, JACS 2002, JACOBSEN – UREA RATIONAL DESIGN (MACHOISM)

Jacobsen, JACS 2002, JACOBSEN – MANNICH (NO STUDY)

Jacobsen, JACS 2004, 4102 JACOBSEN – HYDROPHOSPHONYLATION (NO STUDY)

Jacobsen, JACS 2004, 4102 JACOBSEN – HYDROPHOSPHONYLATION (NO STUDY)

Jacobsen, JACS 2004, JACOBSEN - PICTET-SPENGLER

Jacobsen, JACS 2004, JACOBSEN - PICTET-SPENGLER (NO STUDY)

Jacobsen, JACS 2004, JACOBSEN - PICTET-SPENGLER (NO STUDY)

Jorgensen, ACIEE 2000, 3559 JORGENSEN – REVIEW ON HDA Warning, the following slide contains explicit content

Jorgensen, ACIEE 2000, 3559 JORGENSEN – REVIEW ON HDA

Rawal JACS 2000, 7843; OL 2002, 1163; JACS 2002, 4628 (SUBTLE CHIRALITY) RAWAL – LEWIS ACID CATALYZED DA (SALEN-Cr) 1-amino-3-siloxy-1,3-butadienes

Rawal, JACS 2002, 4628 RAWAL - HDA OF UNACTIVATED KETONES Rawal, OL 2002, 3321 Rawal, JACS 2002, 4628

Rawal, OL 2002, 3321 RAWAL - REACTION OF UNACTIVATED KETONES Not due to prensence of DCl

Rawal, OL 2002, 3321; Jurczak, SYNTHESIS 1979, 41 RAWAL – VERY REACTIVE DIENE

Rawal, JACS 2002, 9662 RAWAL – HDA SOLVENT SCAN

Rawal, JACS 2002, 9662 RAWAL - HDA OF UNACTIVATED KETONES Dihydropone Solvolysis Product :

Rawal, JACS 2002, 9662 RAWAL – FIRST GENERAL HDA FOR UNACTIVATED KETONES

Houk-List, JACS 2003, 16; JACS 2003, 2475 MACMILLAN/HOUK/LIST – ORGANOCATALYSIS OTHER THAN H BOND MacMillan, JACS 2000, 4243; TL 2003, 2475

Braddock, Synlett 2003, 1121 BRADDOCK – PHANOLS FOR DA (NOT ENANTIOSELECTIVE)

Göbel, OL 2000, 179 GÖBEL – H BOND ASSISTED ASYMMETRIC DA

Rawal, Nature 2003, 146 RAWAL - FIRST ASYMM. HDA THROUGH HYDROGEN BONDING Ar = 1-naphtyl

Rawal, PNAS 2004, 5846 RAWAL - ALL CARBON ASYMM. DA CAT. BY H-BONDING

Rawal, PNAS 2004, 5846 ALL CARBON DA CAT. BY HYDROGEN BONDING

Rawal, PNAS 2004, 5846 ALL CARBON DA CAT. BY HYDROGEN BONDING More persistent hydrogen bond at lower temperatures

Rawal, PNAS 2004, 5846 RAWAL - ALL CARBON DA CAT. BY HYDROGEN BONDING REACTION WORK BEST WITH ALPHA SUBSTITUTION; MACMILLAN: BEST WITH BETA SUBSTITUTION (COMPLEMENTARY)

Literature Meeting - Charette Group – Marc K. Janes – December 6 th 2004 THE END Eric N. Jacobsen Viresh H. Rawal Pioneers for a new mode of asymmetric catalysis involving one one the most important bond in nature?

Schaus, JACS 2003, T

Ref or note TITLE

Göbel, OL 2000, 179 GÖBEL – H BOND ASSISTED ASYMMETRIC DA

Göbel, OL 2000, 179 GÖBEL – H BOND ASSISTED ASYMMETRIC DA

Göbel, OL 2000, 179 GÖBEL – H BOND ASSISTED ASYMMETRIC DA

Note or ref TYPES OF ACID CATALYSIS

Hine, JOC 1985, 5096; JOC 1987, 2083; Kelly, TL 1990, 2083 DOUBLE HYDROGEN BONDING - SEMINAL WORK

Schreiner, Chem. Soc. Rev. 2003, 289; Chem. Euro. J. 2003, 407 TITLE