309
J. Am. Chem. SOC.1988, 110, 309-310 for applications in organic synthesis, solutions are being sought to the unfavorable deinsertions of these complexes relative to their annulations with acetylenes, and also based on the successful stereoselective akylation of the benzyl complex 8, the possibility of asymmetric induction in reactions at the carbon-nitrogen bond of the imino ligand are being examined.
Acknowledgment. This work was supported by the National Institutes of Health (PHS-GM 33589). The National Institutes of Health has provided a predoctoral training grant for D.C.Y. (GM 07151). The N M R instruments used were funded in part by the N S F Chemical Instrumentation Program and by the NCI via the University of Chicago Cancer Research Center (CA14599).
Supplementary Material Available: Spectral and physical data for all new compounds and X-ray crystallographic data for compounds 7,9, and 15a (25 pages). Ordering information is given on any current masthead page.
0.0
50.0
Phony 1b a r o n 1
100.0 c
oc
I d l /[Chymai
150.0 r j p s I n!
Figure 1. Dependence of the "B chemical shift (A) and line width (+) on the molar ratio of phenylboronic acid (fixed at 2.9 m M ) to a-chy-
llB Nuclear Magnetic Resonance Studies of the Structure of the Transition-State Analogue Phenylboronic Acid Bound to Chymotrypsin' Foluso Adebodun and Frank Jordan* Department of Chemistry Rutgers. The State University of New Jersey Newark, New Jersey 07102 Received August 3, 1987 Several solution kinetic studies have suggested that the serine protease class of enzymes is subject to reversible inhibition by boric acid and boronic acid derivatives.2 X-ray crystallographic studies of boronic acids attached to a-chymotrypsin (cx-CHT)~and subtilisin4 demonstrated that the boron atom is in a tetrahedral environment covalently bonded to the active center serine. Raman spectroscopic studies further supported this finding in the solid state.5 We report IlB N M R studies on phenylboronic acid (PBA) in the absence and presence of a-CHT at pH 7.2, 22 OC, and our ability to deduce the solution structure around the boron atom when enzyme-bound. Under conditions of fast exchange of the boron nucleus between the bound and free states, both the chemical shift and the relaxation rates of the nucleus can be deduced from a "titration" of the boron resonance with limiting amounts of a-chymotrypsin. For IlB (I, the nuclear spin is 3/2) in the limit of extreme narrowing (wI27: 95% yield), which on treatment with t-BuLi underwent a remarkably smooth 1,3-rearrangement to furnish optically pure ( R ) - 2 in 80-95% yield. The details of this process and its application to other phenol derivatives will be reported in due course. For preparation of the starting dibromobinaphthol, see: Lingenfelter, D. S.; Helgeson, R. C.; Cram, D. J. J . Org. Chem. 1981, 46, 393. (7) A typical experimental procedure is exemplified by the reaction of benzaldehyde with the diene 3 (entry 2). To a degassed solution of ( R ) (+)-3,3'-bis(triphenylsilyl)binaphthol (R)-2(Ar = Ph) (88 mg,0.1 1 mmol) in dry toluene ( 5 mL) was added a 0.5 M hexane solution of Me3A1 (0.2 mL, 0.1 mmol), and the resulting wine-red solution was stirred at rmm temperature for 1 h. After having been cooled to -20 OC, benzaldehyde (0.102 mL, 1 mmol) and the diene 3 (220 mg, 1.1 mmol) were added. The mixture was stirred at -20 OC for 2 h, poured into 10% HCI, and extracted with ether. The combined extracts were concentrated in vacuo to give the crude adducts which were redissolved in CH2C12 (30 mL) and treated with trifluoroaceiic acid (0.092 mL, 1.2 mmol) at 0 'C for 1 h. The reaction mixture was then poured into saturated NaHCO,, extracted with CHZCI2,and dried over Na2S0,. Evaporation of solvent and column chromatography of the residue on silica gel, eluting with 1:3 ether/hexane, gave a mixture of cis-dihydropyrone 4 (1 56 mg,77%; [o(]D+7.1° ( c 1.0, CHCI,)) and the trans isomer 5 (14 mg,7%; [aID -27.3' ( C 0.75, CHCI,)). (8) The optical purity of the trans adduct 5 was 52% ee. (9) The isomeric ratios of the dienes in Table I are as follows: 6 ( E / Z = 84:16); 7 ( E / Z = ] : I ) .
0002-7863/88/ 15 10-0310%01.50/0 0 1988 American Chemical Society
