Cathedrals of science · Cathedrals of science “There are ancient cathedrals which, apart from...
Transcript of Cathedrals of science · Cathedrals of science “There are ancient cathedrals which, apart from...
Cathedrals of science“There are ancient cathedrals which, apart from their consecrated purpose,
inspire solemnity and awe. Even the curious whisper reverberatesthrough the vaulted nave, the returning echo seems to bear a message ofmystery. The labor of generations of architects and artisans has beenforgotten, the scaffolding erected for the toil has long since beenremoved, their mistakes have been erased, or have become hidden bythe dust of centuries. Seeing only the perfection of the completed whole,we are impressed as by some superhuman agency. But sometimes weenter such an edifice that is still partly under construction; then the soundof hammers, the reek of tobacco, the trivial jests bandied from workmanto workman, enable us to realize that these great structures are but theresult of giving to ordinary human effort a direction and purpose.
Science has its cathedrals, built by the efforts of a few architects and manyworkers…..
Gilbert Lewis, from the preface toThermodynamics and the FreeEnergy of Chemical Structure
LangmuirLewis
Early experiments designed to describethe transition states of reactions
Eschenmoser Dunitz Baldwin
Trajectory ofattack during SN2
Experimentalevidence that
clarifies shape ofσ*
Trajectory of attackon carbonylsExperimentalevidence that
clarifies shape of π*
Rules to predictwhen
intramolecularattack occurs
When is HOMO-LUMO overlap
possible?
How do we know that trajectory of attack duringan SN2 reaction is 180o?
R3N Br nN !*C-Br
Early experiments designed to describethe transition states of reactions
Trajectory of attackon carbonylsExperimentalevidence that
clarifies shape of π*
Dunitz
The Bürgi-Dunitz Angle: Experimental Evidence from CrystalStructures of 1,8-Disubstituted Naphthalenes
OCCH3CH3O
Procter, G.; Britton, D.; Dunitz, J.D. Helv. Chim. Acta 1981, 64, 471-477.
The Bürgi-Dunitz Angle (105o ± 5)
“…a decrease in N-C=O distance beingaccompanied by an increase innonplanarity at the carbonyl carbonand a slight lengthening of the C=Odistance.”
Bürgi, H.B; Dunitz, J.D. Acc. Chem. Res. 1983, 16, 153-161.
ORR
N
α
A reminder of Bürgi and Dunitz en route to a mitosane…
Papaioannou, N.; Blank, J.T.; Miller, S.J J. Org. Chem. 2003, 68, 2728-2734.
in the crystal structure of an intermediate (12):
Early experiments designed to describethe transition states of reactions
Baldwin
Rules to predictwhen
intramolecularattack occurs
When is HOMO-LUMO overlap
possible?
Baldwin’s Rules for Ring Closure
Baldwin, J.E. J.Chem. Soc., Chem. Comm. 1976, 734-736.Enolates: Baldwin, J.E.; Lusch, M.J. Tetrahedron 1982, 38, 2939-2947.
Favored: exo-tetexo-trigendo-dig
Disfavored: 3,4-exo-dig5-, 6-, 7-endo-tet3-, 4-, 5-endo-trig
✔✔✖✔✔✔7
✔✔✖✔✔✔6
✔✖✖✔✔✔5
✔✖✖✔✔4
✔✖✖✔✔3
Dig (sp)Trig(sp2)
Tet(sp3)
Dig(sp)
Trig(sp2)
Tet(sp3)
RingSize
ENDOEXO
✔✔✔✔7
✔✔ ✔✔✔6
✖✖✔✔5
✖✖✔✔4
✖✖✔✔3
Trig(sp2)
Tet(sp3)
Trig(sp2)
Tet(sp3)
RingSize
(ENOLENDO)-EXO
(ENOLEXO)-EXO (Enolendo) - ketone is IN the ring
(Enolexo) - ketone is OUT of the ring
(Remember Eschenmoser’s examples)
Baldwin’s Rules - the Endo-Dig preference
Computational studies suggest that geometry of attackof π* should be similar for alkynes and alkenes:
Attacking σ* Attacking π*(the Bürgi-Dunitz angle)
?!?! Not attacking π* ???
Strozier, R.W.; Caramella, P.; Houk, K.N. JACS 1979, 101, 1340-1343
OCCH3N
As do crystal structures:“…not only does the nitrile group appear to becomparable in strength to the carbonyl group as anelectrophile in these compounds, but also thepreferred approach angle Nu. . . C-X must be verysimilar in the two classes of molecules.”
Procter, G.; Britton, D.; Dunitz, J.D. Helv. Chim. Acta 1981, 64, 471