Enantiomerically pure monophosphines bearing phosphetane units have been prepared from primary phosphines and the cyclic sulfates of anti-1,3-diols. Various substituents have been introduced on both the phosphorus and the ring carbon atoms, thus showing the high flexibility of the synthetic approach. The same synthetic method has been applied to the preparation of P-N heterobidentate ligands bearing phosphetane and azetidine rings. The final products have been characterised by X-ray diffraction studies.Structural modularity is a key feature for chiral ligands in order to be broadly useful in enantioselective catalysis. Thus, whenever a new efficient synthon or concept for ligand design has been highlighted, the versatility of the corresponding synthetic approach must be checked in a systematic fashion to ensure optimisation of the properties of these ligands for any given purpose. This is the case for the chiral synthons I, namely the 2,4-disubstituted phosphetane moieties, which are easily accessible from enantiomerically pure 1,3-diol derivatives. They have already been used for the synthesis of diphosphine ligands, II, highly efficient in enantioselective ruthenium and rhodium catalysed hydrogenations. 1 The nature of the phosphetane-connecting scaffold in II modulates the catalyst efficiency and opens, for instance, specific application fields to the bis-phosphetanoferrocenes (X = 1,1'-ferrocenediyl) with respect to the bis-phosphetanobenzenes (X = 1,2-phenylene) or bis-phosphetanoethanes (X = 1,2-ethanediyl) (Figure 1).Within a single family of bis-phosphetanes II, the steric properties of the ligands have been finely tuned by variations of the R substituents, as the chiral anti-1,3-diols required for their synthesis are very easily available via asymmetric hydrogenation of the corresponding 1,3-diketones. 2 As application field for chiral phosphetanes, previous work considered mainly catalytic hydrogenations, which founded the choice of bidentate, C 2 -symmetric phosphines as target structures. However, phosphetane-based ligands could also be designed for a number of other catalytic applications and, therefore, new variations of the general structure I are highly desirable. In this context we present here the synthesis and characterisation of new monodentate phosphetanes as well as the first examples of P-N heterobidentate phosphetanes.Generally speaking, the successful use of bidentate ligands in many asymmetric catalytic reactions obscures the field of chiral monodentate phosphines. Nevertheless, recent literature data provide clear evidence for the specific catalytic applications of monodentate phosphorus ligands and point out the crucial need for efficient chiral phosphines of this family. 3 In this context, monodentate phosphetanes could be interesting tools as they are readily available from virtually any primary phosphine and a number of 1,3-diols, according to the synthetic approach shown in Scheme 1. Consequently, after our initial report on the synthesis of 1a (R' = Ph, R = Me) and 2 (R' = Mesityl...

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The a,b,g,d-unsaturated 2,4,5-trimethoxyanilides 8a-e which bear a terminal alkenyl side chain at the 3-position were prepared from 1,2,4-trimethoxybenzene (2) in four steps and 25-41% overall yield. Attempted ring closing metathesis reactions were successful in the presence of catalysts 9 for the substrates 8c-e and led to the products 10c-e (66-91% yield). Substrates 8a and 8b with a shorter alkenyl side chain did not cyclize.Geldanamycin (1) (Figure) is an ansamycin antibiotic which was isolated from Streptomyces hygroscopicus var. geldanus var. nova (UC-5208). 1 The compound has recently attracted considerable attention due to its antitumor activity. 2 A derivative of geldanamycin, 17-allylamino-17-demethoxygeldanamycin, awaits phase II clinical trials as an antitumor agent. 3 The mechanism of action in cells is based on an inhibition of nucleotide binding to the molecular chaperone heat shock proteine (Hsp) 90. 4,5 Additional studies suggest that the binding to Hsp90 is not the only cellular interaction responsible for the observed activity. 6 The biological importance of geldanamycin makes itself and simpler analogs thereof interesting target compounds for de novo synthesis. 7,8 Structurally, geldanamycin is related to the ansamycin antibiotics macbecin I 9 and herbimycin A 10 syntheses of which have been previously reported. The macrolactam ring of these compounds has been formed by conventional macrolactamization. FigureWe envisioned the ring closing metathesis 11 of a suitable 1,w-diene to be a new and general approach to the geldanamycin skeleton. The prerequisite starting material bears a 2-methylpenta-2,4-dienoic acid anilide the terminal double of which would undergo the metathesis reaction with an internal terminal alkene. As literature precedent for such a metathesis was rare 12,13 we undertook model studies the preliminary results of which are reported in this communication.

Two chiral ansa-bridged lactams ([16]metacyclophanes) 2a,b were synthesized starting from 2-methoxyhydroquinone diisopropyl ether (6) in 14 (2a, 3.9% overall) and 16 synthetic steps (2b, 0.6% overall). Both compounds contain typical features of geldanamycin (1) in the C-1 to C-9 part of the ansa chain, i.e. the a,b,g,dunsaturated anilide (C-1 to C-5), the carbamate at the stereogenic carbon atom C-7 and the E-double bond between C-8 and C-9. While the rest of the ansa chain (C-10 to C-15) was an alkyl chain in compound 2a, a more polar CH 2 OCH 2 CH 2 OCH 2 chain was installed in compound 2b. Key step of the sequence was a ring-closing metathesis in which the ansa compounds 3 were formed as a mixture of isomers. Deprotection and oxidation to the quinone failed for diisopropyl ether 2b but was successfully conducted with precursor 2a.

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