Doubly Stereodifferentiating Hiyama Addition with Mismatched Reactants; Enantio- and Diastereo- controlled Synthesis of Dihydrocanadensolide ** By Johann Mulzer* and Lars Kattner Dedicuted to Profkssor Roy Huisgen on the occasion of his 70th birthday Owing to its four chirality centers and the bicyclic para- conic acid lactone structure, dihydrocanadensolide 1, a metabolite of Penicillium canadense,['l is an attractive syn- thetic target molecule. The configuration first proposed for 1 was later r e v i ~ e d [ ~ > ~ ] but is still not unequivocally elucidated. [I] N N. Greenwood, A. Earnshaw: Chemisrry o/ rhe Elemcnrs. Pergamon, Oxford 1984: Chemie der Elemente, VCH Verlagsgesellschaft. Weinheim 1988. [2] J. lander. J. Knackmuss, L U. Thiedemann, 2. Nururfursrh. B30 (1975) 464. [3] J. .lander. U. Engelhardt in C. B. Colburn (Ed.): Developments in Inurgunic Nitrogen Chemisrr-v, Vui. 2. Nirrugen Compounds uJChiorine, Bromine, and Iodine. Elsevier. Amsterdam 1973, p. 184. [4] The names nitrogen triiodide. nitrogen bromide and nitrogen chloride conform to IUPAC nomenclature, although the actual polarization would be better described as trlhalide nitride. 151 a) H. Hartl, H. Bdrnighausen, J. Jander. Z. Anorg. ANg. Chem. 375 (1968) 225: b) J. Jander, L. Bayersdorfer, K. Hohne, ibid. 357 (1968) 215. [6] I. Tornieporth-Oetting, T. Klapotke, J. Passmore. 2. Anurg. A&. Chem.. in press. [7] R. H Davies, A. Finch, P N. Gates, J Chem. Sur. Chen?.Cummun. 1989, 1461. [8] 0. Glemser, H. Haeseler. 2. Anurg. AlIg. Chem. 279 (1955) 141. [9] Warning: Although pure NI, IS stable at low temperatures in CFCI,. the synthesis and isolation presents particular problems. On occasion the reac- tion of BN with IF does not start immediately. One of our samples cooled to ~ 18 'C and covered with a 10-cm thick layer of ice exploded and flying splinters caused considerable damage, for example to the full visor face protection of the experimenter. [lo] In the reaction of BN with four equivalents of IF, analogous to Equation (a). NI,, is also formed. Byproducts: I,BF, and an, as yet, not unambigu- ously identified yellow solid. possibly IFYBF?: 2 BN + 8 IF + 2 NI, + 2 BF, + 2 IF + 2 NI, + BF, + I,FeBF?; 2 I,F@BF? + I,eBFF + IF$aBF,O. U p till now no indication of the existence of NIfBF? could be [l 11 A rough estimate of the enthalpy of reaction for Equation (b). neglecting the correct aggregation states, yields AH;98 (c) = - 312 kJ mol-' (AW<: + 287 kJ mol-' [7]. [12] Excitation wavelength: 647.09 nm, Laser energy' 15 mW. T:- 100°C. ;[cm-'] = 72(m). 91(m), 113(vw), 146(m), 179(vw), 279(s), 354(w); Note added in proof: In the meantime it has also been possible to record a '%NMR spectrum of NI, (98% ''N) in CFCI, [20]. The appearance of only one singlet [a = + 183 ppm, rel. to MeNO,. 50.653 MHz (I5N). - 30 C] in the expected range points to the presence of only one species in solution. We shall report on the measurement conditions and the synthe- sis of "NI, in a further communication.. [I31 a) K Knuth, J. Jander, U. Engelhardt, Z. Nururfursch B 24 (1969) 1473; b) %. Ai70rg. AlIg. Chem. 392 (1972) 279; c) J. Jander. Adv. Inorg. Chem. Radiochem. 19 (1976) 1 [14] K. Dehnicke. Angew Chem. 88(1976)612; Angen Chem. Inr. Ed. Eng/. 15 (1976) 240. 1151 P. J Hendrd, J. R. Mackenzie, Chem. Commun. 1968, 760. [16] Depending on the temperature a residue which is either brown "1,. NHJ. (room temperature. excess NH, in the gas phase), green "1,. 3 NH,]. (- 33 P T> -7S'C) or red [NI, - 5 NH,], (T < -75°C) remains [4]. but NI, cannot be recovered by removal of NH, in vacuo. ABr i Y cH3 # n-C4HS - 3 4: kX CH3 OH found. 2 BN(soln.) - 2541191, 1F(g) - 95[18], BF',(g) - 1137[18], NIJgj OBn // GMOM o q n - c 4 H 9 OMOM b,c,d CH3* I 4 5 [17] 'H NMR (CDCI,): ii(Me,NeIe) = 3.02; cf. 6(MeI) = 2.17. [18] D. A. Johnson. Some Thermodynamic Aspem of Inorganic Chemislrj, 119) I. Barin- Thermorhemicul Datu of Pure Subsrances, Purr 1. VCH Verlags- [20] We thank Dr. KlLw?. BASF AG, for recording the 15N-NMR spectrum. Cambridge University Press. Cambridge 1982. gescllschaft, Weinheim 1989. a - oHCyoMoM n-C4H9 3 e, f - 1 The physiological properties of the compound are un- known. We report here on the total synthesis of natural 1 and its enantiomer (Scheme 1). Scheme 1. a)CrCI,/LiAIH,, THF, OT, 36h. 63%; b) Na/NH,,, THF. - 40 'C. 20 min, 86%; c) pyridinium p-tosylate (PPTS), MeOH, 22 C, 24 h, 64%; d) HJO,, Et,O/THF, 2 2 ° C 10 min, pyridinium chlorochromate (PCCj. CH,CI,. 22T, 2 h, 85%; e)HCI/MeOH/THF, 60°C. 1 h, 98%; f)O,/PPh,, CH2CI,. -78°C; PCC, CH,CI,, 22 C, 2 h, 67%. C€ 1 The key step is the Hiyama additionC4] of the ally1 bromide derivative 2 to the aldehyde 3 (MOM = methoxymethyl). Both components are accessible in pure form in a few steps from (R)-2,3-i~opropylideneglycerinaldehyde[~~ and react highly stereoselectively (> 97% according to 'H- and I3C- NMR analysis) to give the adduct 4 (Table 1). This is the first Hiyama reaction of a chirally substituted acyclic ally1 bro- mide derivative.[61 The configuration at the new chirality center C-6 was confirmed by conversion of4 into the diacetal 6, in which the trans position of 6-H and 7-H could be detect- OBn // ed by NOE difference spectroscopy. The relative configura- tion at C-5/6 follows from the successful conversion of the in the case of cis-annelation['] (Scheme I). ["I Prof. Dr. J. Mulzer, DipLChem. L. Kattner Institut fur Organische Chemie der Freien Universitit Takustrasse 3. D-1000 Berlin 33 turaufkliirung niedermolekularer Verbindungen". [**I This work was supported by the Graduiertenkolleg "Synthese and Struk- mono1actone into the bislactone which is possible Only Angm'. ('hm7. lnl. Ed Engl. 29 (1990j No. 6 c> VCH Verlug.sgese1ischafi mhH, 0-6940 Wemheim. 1990 M70-0833190/0606-079 S 03.50+ ._7S/O 679