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Borenes and boranes: Silylaminoiminoborenes, such as depicted, were isolated after treatment of halogen triels with silylaminofluoroboranes. In addition, novel aryl- and silyl-substituted diaminofluoroboranes were also prepared in order to substantiate this reaction route.Reactions between the halogen triels AlClMe(2), AlBr(3), GaCl(3) and the silylaminofluoroboranes (Me(3)Si)(2)NB(F)NRSiMe(3) (R=SiMe(3), CMe(3)) afforded the silylaminoiminoborenes, which were isolated as the triel adducts, such as Me(3)Si(Cl(3)Ga)NBNRSiMe(3) (6). In order to extent this reaction path to other fluoroboranes, novel aryl- and silyl-substituted diaminofluoroboranes were synthesised. Because almost no open-chain diaminofluoroboranes had been structurally characterised previously, corresponding fluoroboranes containing no silyl groups were crystallised for purposes of comparison. In complex reactions with the arylsilylaminofluoroboranes [(2,6-(iPr)(2)C(6)H(3))(Me(3)Si)NB(F)NR(2), R=iPr, iBu], amine adducts of borenium salts such as [(iPr)(2)NH-->B(Bu)NH-2,6-(iPr)(2)C(6)H(3)](+)AlCl(4) (-) (13) were obtained.

Spirodionic acid (1), a novel microbial metabolite with a spiro[4.5]decene skeleton, the 6-ethyl-2H-pyrone 5, dihydrosarkomycin (6), and other metabolites were isolated from the strain Streptomyces sp. Tü 6077. Structural elucidation was accomplished by NMR spectroscopic and mass-spectrometric studies, and the biosyntheses of compounds 1, 5, and 6 were investigated by feeding experiments with (13)C-labeled precursors. All results indicate a biogenetic sequence with metabolite 5 and sarkomycin (7) as precursors in the formation of spirocyclus 1 through an intermolecular Diels-Alder-type reaction.

A variety of enantiomerically pure steroidal compounds was synthesized utilizing a sequence of Stille and Heck cross-coupling reactions and subsequent thermal 6pi-electrocyclizations. Highly chemoselective Stille couplings on the triflate moiety of several 2-bromocyclohex-1-enyl triflates with cis- and trans-fused bicyclo[4.3.0]nonenylstannanes furnished the corresponding tricyclic bromobutadienes in good to excellent yields (70-97%). These were subjected to Heck reactions with tert-butyl acrylate to provide pentasubstituted tricyclic 1,3,5-hexatrienes. A significant increase in efficiency could be achieved by applying a novel protocol with a precatalyst on the basis of the palladacycle prepared from Pd(OAc)2 and P(o-Tol)3 with added triarylphosphines as co-ligands (73-90% yield). Upon heating to 205-215 degrees C in decalin or to 140 degrees C in toluene (for certain cases), these hexatrienes yielded (78-90%) various unsaturated steroid analogues as single diastereomers. A particular oxohexatriene, obtained after deprotection of an adjacent carbonyl group, underwent 6pi-electrocyclization at the unusually low temperature of 140 degrees C to yield (75%) an interesting 7-carboxyl-substituted steroidal dienone. Attempts to remove the remaining protecting groups from some of the other new steroidal compounds under acidic conditions furnished a novel 3-oxo-7-carboxyl steroid analogue and a 3-hydroxy-substituted steroidal diene. A novel estradiol derivative could be obtained in 69% yield from the synthesized steroidal dienone. Deprotection furnished the corresponding unprotected 7-carboxylestradiol in 81% yield.

Novel diastereomerically pure beta-D-galactosidic prodrugs (+)-12 a-e of the cytotoxic antibiotics CC-1065 and the duocarmycins were prepared for an antibody directed enzyme prodrug therapy (ADEPT) using 4 as a substrate via a radical cyclization to give rac-5 and rac-6 followed by a chromatographic resolution of the enantiomers of rac-5, glycosidation and linkage to the DNA-binding units 10 a-e. These only slightly toxic compounds can be toxified enzymatically by an antibody-beta-D-galactosidase conjugate at the surface of malignant cells to give the cytotoxic drugs, which then alkylate DNA. The new prodrugs were tested in in vitro cytotoxicity assays showing excellent QIC(50) values of 4800 and 4300 for (+)-12 a and (+)-12 b, respectively. The absolute configuration of precursor (+)-5 was determined by comparison of the experimental CD spectrum with the theoretically predicted CD spectra and by X-ray structure analysis.

A highly chemoselective sequence of Stille and Heck couplings on the heterocyclic bromoenol triflates 2 a-c with the bicycloalkenylstannanes cis-3 and trans-3 furnished the intermediate bromobutadienes 4 a-c in good yields ranging from 73-94 %. A modified Heck coupling protocol employing the palladacycle 8 and an additional bidentate ligand such as 1,4-bis(diphenylphosphinyl)butane allowed a significant reduction in catalyst loading while still obtaining the heterocyclic 1,3,5-hexatrienes 5 a-c in good yields (71-94 %). The unsymmetrically substituted 1,3,5-hexatrienes 5 a-c in solution underwent 6pi-electrocyclizations following an optimized microwave-heating protocol to yield the steroidal tetracycles cis-7 a-c and trans-7 b (59-69 %). Tetracycles cis-7 a-c are the products of a subsequent 1,5-hydrogen shift to the thermodynamically more stable, more highly substituted diene units. Removal of the tert-butyl groups provided the novel steroidal delta-amino acid 9 a and the delta-amino acid derivatives 9 b, c in good yields (76-86 %).

Reaction of [(eta(5)-Me4EtC5)Fe(II)Cl(tmeda)] (tmeda = N,N,N'N'-tetramethylethylenediamine) with a polyanion solution of decacyclene (1) results in the formation of the triple-deckers [{(eta(5)-Me4EtC5)Fe}2-mu2-(eta(6):eta(6)-decacyclene)] (3) and [{(eta(5)-Me4EtC5)Fe}4-mu4-(eta(6):eta(6):eta(6):eta(6)-decacyclene)] (4). Metal complexation in 3 and 4 occurs on opposite faces of the pi perimeter in an alternating mode. The decacyclene ring adopts a gently twisted molecular propeller geometry with twofold crystallographic symmetry (C2). Complex 4 crystallizes in the chiral space group C222(1); the investigated crystal only contains decacyclene rings with M chirality. The handedness can be assigned unambiguously to the presence of the iron atoms. Cyclovoltammetric studies revealed quasireversible behavior of the redox events and a strong interaction of the Fe atoms in 3 and 4, exemplified by potential differences deltaE of 660 and 770(780) mV between the first and the second individual oxidation processes. This corresponds to a high degree of metal-metal interaction for 3 and 4. The successful syntheses of 3 and 4 together with earlier results from our laboratory proves that all five- and six-membered pi subunit sets of 1 are prone to metal complexation. A clear site preference in 1 towards the complexation of [Cp(R)]iron, -cobalt, and -nickel fragments exists.

The (E,Z,E)-1,3,5-hexatrienes 1a, 2a,b and 3b undergo 6pi-electrocyclization within 15-30 min upon heating to 200-215 degrees C. While the cyclohexene-annelated products 8a,b were stable, the analogous cyclopentene- and cycloheptene-annelated derivatives 7a and 9b easily underwent dehydrogenation to the corresponding aromatic compounds 10a and 12b during the work-up. The cyclohexadiene derivatives 8a,b were employed in thermal Diels-Alder reactions with 4-phenyl-3H-1,2,4-triazoline-3,5-dione (PTAD) and tetracyanoethylene (TCNE) to give the expected [4+2] cycloadducts 13a and 14a in good yields (60 and 78%). The initially formed cycloadduct of 8a and dimethyl acetylenedicarboxylate (DMAD) underwent a subsequent retro-Diels-Alder reaction to give the tetrahydronaphthalene 11b (47%). Under high pressure (10 kbar), the cycloadduct 15a was formed at room temperature and could be isolated in 44% yield. TCNE and N-phenylmaleimide with 8a under high pressure also led to the [4+2] cycloadducts 14a and 16a in good yields (60 and 77%). The 6pi-electrocyclization and subsequent Diels-Alder reaction, when performed as a one-pot domino process, provided direct access to Diels-Alder products of intermediately formed 6pi-electrocyclization products, for example from the 1,3,5-hexatrienes 1a,b, 2a,b, 3b and TCNE to the corresponding tricyclic products 17a,b, 14a,b, 18b in moderate to good yields (27-80%) depending on the nature of the alkoxycarbonyl group. Such sequential reactions with N-phenylmaleimide, maleic anhydride, dimethyl maleate and fumarodinitrile, the latter two under high pressure (10 kbar), worked as well to yield 16b (70%), 19a,b (19, 32%) and 20b (39%) and 21b (76%), respectively. With PTAD, however, the hexatrienes 2a,b reacted at ambient temperature without 6pi-electrocyclization to give the formal [4+2] cycloadducts 27a,b (48 and 46%), most probably via zwitterionic intermediates 23a,b and 25a,b.

Palladium-catalyzed sixfold coupling of hexabromobenzene (20) with a variety of alkenylboronates and alkenylstannanes provided hexaalkenylbenzenes 1 in up to 73 % and 16 to 41 % yields, respectively. In some cases pentaalkenylbenzenes 21 were isolated as the main products (up to 75 %). Some functionally substituted hexaalkenylbenzene derivatives containing oxygen or sulfur atoms in each of their six arms have also been prepared (16 to 24 % yield). The sixfold coupling of the less sterically encumbered 2,3,6,7,10,11-hexabromotriphenylene (24) gave the desired hexakis(3,3-dimethyl-1-butenyl)triphenylene (25) in 93 % yield. The first successful cross-coupling reaction of octabromonaphthalene (26) gave octakis-(3,3-dimethyl-1-butenyl)naphthalene (27) in 21 % yield. Crystal structure analyses disclose that, depending on the nature of the substituents, the six arms are positioned either all on the same side of the central benzene ring as in 1 a and 1 i, making them nicely cup-shaped molecules, or alternatingly above and below the central plane as in 1 h and 23. In 27, the four arms at C-1,4,6,7 are down, while the others are up, or vice versa. Upon catalytic hydrogenation, 1 a yielded 89 % of hexakis(tert-butylethyl)benzene (23). Some efficient accesses to alkynes with sterically demanding substituents are also described. Elimination of phosphoric acid from the enol phosphate derived from the corresponding methyl ketones gave 1-ethynyladamantane (3 b, 62 % yield), 1-ethynyl-1-methylcyclohexane (3 c, 85 %) and 3,3-dimethylpentyne (3 e, 65 %). 1-(Trimethylsilyl)ethynylcyclopropane (7) was used to prepare 1-ethynyl-1-methylcyclopropane (3 d) (two steps, 64 % overall yield). The functionally substituted alkynes 3 f-h were synthesized in multistep sequences starting from the propargyl chloride 11, which was prepared in high yields from the dimethylpropargyl alcohol 10 (94 %). The alkenylstannanes 19 were prepared by hydrostannation of the corresponding alkynes in moderate to high yields (42-97 %), and the alkenylboronates 2 and 4 by hydroboration with catecholborane (27-96 % yield) or pinacolborane (26-69 % yield).

The Lewis acid mediated cyclization of epoxides with 1,3-bis(trimethylsilyloxy)-1,3-butadienes, electroneutral equivalents of 1,3-dicarbonyl dianions, results in the formation of 2-alkylidenetetrahydrofurans with a great variety of substitution patterns and functional groups. This includes the synthesis of 2,3'-bifuranylidenes and 7-oxabicyclo[4.3.0]nonanes. The cyclization of dienes with functionalized epoxides containing base-labile groups proceeds with good chemoselectivity. In all reactions, good regio- and E diastereoselectivities are observed. Based on the stereoselectivities observed for reactions of 1,2-disubstituted epoxides, a working hypothesis for the mechanism of the reaction is suggested.