In general, very good to see referrals to previously discussed material given as page numbers rather than chapter numbers as it was in the previous edition. Also good to see that the Harvard and Princeton chemistry departments have people who have done very good work (Evans, MacMillan, Jacobsen).
p. 1108 The top face of cyclopentadiene is shielded by the ethyl groups attached to Al. In the second example, the Al isn’t attached to anything, presumably something like AlCl3.
1110 — The trans enolate in the top line would be less stable regardless of the orientation of the isopropyl group. Once this is established, the orientation of the isopropyl group gives an incoming electrophile just one way to attack. Essentially the oxazolidinone gives you a twofer. A pleasure to see exquisite stereochemistry re-emerge after the previous chapter on organometallic chemistry.
p. 1111 – “less than a milligram of a chiral compound can be passed down a narrow column containing silica modified which a chiral additive.”
1113 — The 3 dimensional visualization tools for sparteine given by the book’s web link is incredibly helpful, particularly since I don’t have a set of molecular models. I used to use something called Dreiding models which were very good. Apparently Aldrich still sells them, but I had trouble with their catalog. Does anyone know if they’re still available?
1115 How is Tosyl 1,2 phenylendiamine (TsDPEN) actually made so that you get one enantiomer. What is the chiral starting material. Or do they just crystallize it using an enantiomerically pure chiral compound?
1118 — Why does using ruthenium instead of rhodium broaden the number of substrates undergoing asymmetric hydrogenation.
1123 — What is the geometry of the salen complex of Mn shown at the top of the page.
1124 — It isn’t clear just where the Oso4 sits in DHQD2PHAL or DHQ2PHAL. Perhaps this isn’t known?
1127 — If you use a different diastereomer of the chiral amino alcohol, do you get a different enantiomer of the product of the aldehyde with diethyl zinc?
Out of order, but there are 3 great papers in the 26 Oct Science (vol. 338 pp. 479 – 480, 500 – 503, 504 – 506 ’12) on selective formation of one diastereomer or enantiomer using an asymmetric organometallic catalyst. The first is particularly interesting as it puts a transition metal catalyst catalytic site of a protein. Here’s some more about it
Streptavidin is protein produced by a microorganism (Streptomyces avidini) which binds biotin very tightly (Kd is 10^-15}. The binding pocket for biotin is large, and the authors hooked a Rhodium complex to the biotin via derivatizing a Rhodium pentamethyl cyclopentadiene ligand so it was covalently attached to the biotin. Then they threw a benzamide derivative + acrylamide at the protein metalloenzyme complex. Apparently everything fit within binding site for biotin within the streptavidin so they actually got out a dihydroisoquinolone. They achieved a 100 fold acceleration in rate (compared to the activity of the isolated rhodium complex) and even better the enantiomeric ratio was ‘as high as ’93:7. So this is aromatic C-H activation within the confines of a protein. Slick
The second paper is more general in that it uses a derivatized cyclopentadiene Rhodium L1, L2 system. The cyclopentadiene is fused to a saturated cyclohexane ring with substituents hanging off it to create a steric environment such that the L1 (large) and L2 (small) are forced to lie in particular directions. Then the reaction begins.
1128 — Organocatalysis — so that’s what MacMillian did to become chemistry chief at Princeton ! Clever stuff.