10078 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA J. Am. Chem. SOC. zyxwvu 1992, 114, 10078-10079 as well as a bidentate Aspl 12 carboxylate and possibly an axial carbonyl oxygen of Gly45 or a water molecule.I0 It is well established that the unusual distorted trigonal py- ramidal (pseudotetrahedral) coordination geometry of blue copper is forced on the metal ion by the rigidity of the polypeptide scaffold in the binding-site region (rack-induced b ~ n d i n g ) . ' ~ ~ ~ . ' * J ~ zyxwvu Ow' to the geometrical constraints imposed by the aspartate side cham, however, formation of a planar copper carboxylate group would require substantialrearrangement of the protein structure.20 Since a large distortion of the protein structure is energetically unfa- vorable, it is likely that the copper is displaced significantly from the plane of the Aspl 12 carboxylate group in forming the Cu- N202(0)structure. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Acknowkdgment. We thank zyxwvuts Dr. David B. G dm of the Scripps Research Institute for assistance with the EPR measurements. This work was supported by grants from the National Institutes of Health (DK19038 to H.B.G.; GM16424 to J.H.R.; GM07616 traineeship to T.J.M.). (18) (a) Malmstrijm, B. G. In Oxidases und Reluted Redox Systems; King, T. E., Mason, H. zyxwvutsrqpo S., Morrison, M., Eds.; Wiley: New York, 1965; Vol. zyxwvuts 1, pp 207-216. (b) Gray, H. B.; Malmstrbm, B. G. Comments Inorg. Chem. 1983, 2, 203-209. (19) (a) Gray, H. B.; Solomon, E. I. In Copper Proteins; Spiro, T. G., Ed.; Wiley: New York, 1981; pp 1-39. (b) Ainscough, E. W.; Bingham, A. G.; Brodie, A. M.; Ellis, W. R.; Gray, H. B.; Loehr, T. M.; Plowman, J. E.; Noms, zyxwvutsrq G. E.; Baker, E. N. Biochemistry 1987, 26, 71-82. (20) Computer modeling of Cu"-Cysl l2Asp azurin coordination was based on the 2.7 . & resolution structure of P. uerugitwsa azurin (ref la). The Cysll2 side chain of wild-type azurin was replaced by an aspartate side chain using Biograf (Version 2.20) from BIODESIGN, Inc. The backbone atoms were fixed while the C, and C, atoms of the aspartate side chain were positioned as closely as possible to the C and S, atoms of cysteine, and the C& bond was rotated to make a pseud square planar base containing the imidazole nitrogens of His46 and His1 17 and the carboxylate oxygens of Aspl 12. In this configuration, C, of Aspl 12 is forced well out of the plane defined by the copper center and the carboxylate oxygens. For a discussion of metal binding to isolated carboxylate groups in proteins, see: Glusker J. P. Adu. Protein Chem. 1991,42, 1-76. Formyltriisopropylsilane: The Synthesis and Chemistry of a Stable Formylsilane John A. Soderquist* and Edgar I. Miranda' Department of Chemistry, University of Puerto Rico Rio Piedras, Puerto Rico 00931 Received July 3, 1992 The only formylsilane isolated as a stable compound, (Me3Si),SiCH0, reported by Tilley et al.z in 1988, represented an impressive synthetic achievement, being prepared from a mixed cyclopentadienyl acylzirconium precursor. Unlike Me3SiCH0,3*4 (Me3Si)3SiCH0 was found to be thermally stable although it decomposes exothermically in airs2 We wish to report the con- venient preparation of formyltriisopropylsilane (2) from a modified dithiane-based approach and its fascinating chemistry. Previously, we have found that the triisopropylsilyl (TIPS) group not only significantly retards nucleophilic substitution at silicon but also greatly impedes reactions at adjacent centems This (1) US. Department of Education Graduate Fellowship (P200A90203). (2) (a) Elsner, F. H.; Woo, H.-G.; Tilley, T. D. J. Am. Chem. SOC. 1988, 110, 313. (b) PhlSiCHO was very recently generated in solution from a related zirconium precursor and identified as a stable compound (Woo, H.-G.; Freeman, W. P.; Tilley, T. D. Orgunometullics 1992, 11, 2198). See also: Sommer, L. H.; Bailey, D. L.; Goldberg, G. M.; Buck, C. E.; Bye, T. S.; Evans, F. J.; Whitmore, F. C. J. Am. Chem. SOC. 1954, 76, 1613. (3) Ireland, R. E.; Norbeck, D. W. J. Org. Chem. 1985, 50, 2198. (4) Linderman, R. J.; Suhr, Y. J. Org. Chem. 1988, 53, 1569. (5) (a) Soderquist, J. A.; Colberg, J. C.; Del Valle, L. J. Am. Chem. Soc. 1989, 111, 4873. (b) Soderquist, J. A,; Rivera, I.; Negron, A. J. Org. Chem. 1989.54, 405 1. (c) Soderquist, J. A.; Anderson, C. L.; Miranda, E. I.; Rivera, I.; Kabalka, G. W. Tetrahedron Len. 1990,31,4677. (d) Santiago, B.; Lopez, C.; Soderquist, J. A. Tetrahedron Left. 1991, 32, 3457. 4b (+)-E ia Fipe 1. MMX minimum energy structures for 4b, (+)-8, and 12. suggested that 2 should be stable, and 3 appeared to us to be its ideal precursor. By modifying the Corey-Seebach approach6 to acylsilanes' to include an intermediate dithiane - acetal exposure of this sensitive system**9 to the dithiane hydrolysis conditions could be essentially avoided. The reaction of 2-lithio-1,3-dithiane6 with TIPSCl (3 h, -78 - 25 "C) gives 1 cleanly (96%, >99% GC purity, bp 120 OC, 0.1 Torr, 87% from MeOH/H20, mp 45.5-47.5 "C). The sol- volysis of 1 was carried out (HgC12, HgO, MeOH),6b which afforded 3 as a colorless liquid (bp 72 OC, 0.6 Torr) in 89% yield. The hydrolysis of 3 on a 50-mmol reaction scale was optimized employing LiBF4 (0.37 M, 1.04 equiv)l0 in refluxing aqueous MeCN (9:91, 15 s), providing pure 2 as a greenish-yellow liquid in 91% yield (bp 85 "C, 3 Torr, 99% GC purity). By contrast, even the mild Vedejs-Fuchs hydrolysis conditions" gave 2 in significantly lower yield and purity (4776, 97% GC purity con- taining 3% TIPSOH), and the standard aqueous MeOH condi- tions6 result in a mixture of 2 and 3. 0 n 1 2 I IHgC$/HC OMe LIEFl zyxw 1 MeOH HxSi(i-Pr)3 H20/MeCN 8% 3 91% As anticipated,2 the spectral properties of 2 are considerably Si-shifted (e.g., IH NMR 6 12.10 (CHO) ppm; I3CNMR 8 249.0 (CHO) ppm; IR (neat) 2588 (vCH), 1651 (vc0) cm-I; UV (THF) 375 (sh, 28), 390 (sh, 59, 406 (86), 426 (87) nm)). The elec- tron-impact MS of 2 provides a weak M' (0.2%), with T I P S (157, 63%) and its degradation products (m/z 73 (67) and 59 (100)) being the major ion fragments. Upon exposure to atmospheric oxygen, 2 spontaneously ignites! Limiting the amount of oxygen produces TIPSOH as the major Si-containing product, and in CDC13solution, minor amounts of TIPSH(D) and TIPSCl are also observed (GCMS), implicating the intermediacy of TIPS radicals in the process. However, air-stable crystalline derivatives of 2 were easily prepared (4a, 2,4-DNP (75%, mp 109-1 10 "C); 4b, tosylhydrazone (87%, mp 63.5-64.5 "C)) as single geometric isomers (anti)I2 (Figure 1). ~~ ~ (6) (a) Corey, E. J.; Seebach, D. J. Org. Chem. 1975,40, 231. (b) Grijbel, B.-T.; Seebach. D. Synthesis 1917, 357. (c) Larock, R. C. Comprehensive Orgunic Transformations; VCH Publishers, Inc.: New York, 1989; pp 721-728. (7) (a) Brook, A. G.; Duff, J. M.; Jones, P. F.; Davis, N. R. J. Am. Chem. SOC. 1967,89,431. (b) Corey, E. J.; Seebach, D. J. Am. Chem. SOC. 1967, 89, 434. (c) Ricci, A.; Degl'Innocenti, A. Synthesis 1989, 647. (d) Bulman Page, P. C.; Klair, S. S.; Rosenthal, S. Chem. Soc. Rev. 1990, 19, 147. (8) Soderquist, J. A,; Hassner, A. J. Org. Chem. 1980.45, 541 (cf. Brook, A. G.; Kucera, H. W. J. Orgunomet. Chem. 1975,87, 263). (9) Soderquist, J. A.; Hassner, A. J. Am. Chem. Soc. 1980,102,1577 (cf. ref 7a). (10) Liphutz, B. H.; Harvey, D. F. Synth. Commun. 1982, 12, 267. (11) Vedejs, E.; Fuchs, P. L. J. Org. Chem. 1971, 36, 366. (12) AMMXE (anti vs syn) = 3 kcal/mol (see Figure 1). Since the submission of this manuscript, a single-crystal X-ray structure of 4b has been obtained (with Dr. C. L. Barnes, University of Missouri) which confirms its anti configuration and the general structural features which are depicted in Figure 1. 0002-7863/92/1514-10078%03.00/0 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA 0 1992 American Chemical Society