The cycloaddition reactions of various C-heteroarylimines with α,β-unsaturated Fischer carbene complexes have been studied. Either [3 + 3] carbocyclization or [3 + 3] and [4 + 3] heterocyclization reactions were accomplished, depending on the structure of the imine and on the type of unsaturation of the carbene complex. Imines derived from furan-, 4, benzofuran-, 5, and N-methylindole-2-carboxaldehyde, 7, gave C3 + C3 cycloadducts 10−12 on reaction with alkynyl carbene complexes 2a and 3. The reaction of N-unsubstituted pyrrole imine 8a with alkenyl carbene complexes 1 involved the ring nitrogen atom of the pyrrole unit leading to C2N + C3 heterocycloadducts 14 and 15. Moreover, N-unsubstituted imines 8 and 9 underwent C2N2 + C3 heterocyclization to alkynyl carbene complexes 2 and 3 to furnish zwitterionic metalpentacarbonyl containing heterocycles 17 and 18. We have studied the thermal behavior of heterocycles 17, finding that they led to bispyrrole 21 or indolizine 20 when heated at 120 °C in the presence and in the absence of carbon monoxide, respectively. The results obtained show that the [3 + 3] cyclizations are promoted by a [1,2]-M(CO)5 shift, while in the case of the [4 + 3] cyclization, a [1,3]-M(CO)5 shift follows the ring-closure step. The X-ray analysis of compound 17b, resulting from 1,3-pentacarbonyltungsten migration, is provided.
Recently, R,β-unsaturated Fischer carbene complexes have been recognized to play an important role in transition-metalmediated organic synthesis. 1 Although alkynyl Fischer carbene complexes are less versatile intermediates than their alkenyl counterparts, a number of useful reactions have been reported; for instance, 1,2-and 1,4-nucleophilic additions 2 as well as [2 + 2], 3 [3 + 2], 4 [3 + 3], 5 [4 + 2] 6 and Pauson-Khand type 7 cyclization reactions. On the other hand, the [4 + 3] cycloaddition of alkenyl carbenes with electron-rich dienes, which may involve a tandem cyclopropanation/Cope rearrangement, has recently emerged as an attractive entry into seven-membered carbocycles; 8 in contrast, no examples of this type of process involving alkynyl complexes are known, perhaps because of the required involvement of a strained cumulene ring. 9 In an extension of this reaction we found that activated 1-azadienes, like 4-amino-1-azadienes and N-hydroxy-1-azadienes, readily undergo [4 + 3] annulation with alkenyl Fischer carbene complexes leading to the azepine ring; interestingly, NMR studies proved that the cycloaddition involves nucleophilic addition of the imine nitrogen to the carbene carbon and cyclization rather than consecutive [2 + 1] cycloaddition and [3,3] rearrangement. 10 On working with alkynyl carbene complexes and nitrogencontaining substrates one can anticipate that either 1,4-or 1,2addition might take place and therefore different reaction pathways should be observed. 11 Reported here is the achievement of a [4 + 3] cycloaddition reaction of alkynyl Fischer carbene complexes with R,β-unsaturated imines as well as the isolation of an η 1 -azepine chromium complex intermediate. 12 The reaction of azadienes 1 with pentacarbonyl methoxy (phenylethynyl)chromium carbene complex 2 (R 3) Ph) in hexane at 20 °C was complete in 3 h affording a precipitate that consisted essentially of the [4 + 3] cycloadducts 3a-c (Scheme 1, Table 1, entries 1-3). When chromium alkynyl complexes 2 having bulky groups at the β-carbon (R 3) SiMe 3 , tert-Bu; entries 4-6) were employed, the cyclization became much more sluggish and therefore required the reaction to be
An asymmetric synthesis of prostanoids containing a six-membered ring core structure (11a-homoprostaglandins), both in solution and using non-cross-linked polystyrene (NCPS) as a soluble support, was developed. Target molecule 1 was generated in a convergent fashion using a three-component coupling strategy, wherein chiral enone (R)-2 was the precursor of the central ring and the cuprate 3 and triflate 4 were used to introduce the side chains. The chiral center of (R)-2 directed the facial selectivity of the conjugate addition reaction which then dictated the stereochemical outcome of the subsequent alpha alkylation. Attachment of a six-membered ring scaffold to NCPS facilitated purification without compromising synthetic yields, still allowed 1H-NMR analysis of the intermediates in the synthesis, and provided an avenue for the construction of six-membered ring prostanoid libraries.
A chemoenzymatic synthesis of the C(21)-C(27) fragment of the marine macrolide family of bryostatin antibiotics is presented. The approach commences from achiral starting materials and has as its crucial step the enzymatic resolution of a racemic mixture of soluble polymer-supported alcohols (syn-10 and syn-11). The immobilized lipase from Candida antarctica (Novozym 435) catalyzes the enantioselective acetylation of syn-10 (in 40% conversion and >99% ee), allowing isolation of the key intermediate (R)-14 in enantiomerically pure form following its cleavage from the poly(ethylene) glycol (PEG) scaffold. The PEG matrix is both compatible with the multipolymer enzymatic transformation and allows for rapid purification and facile NMR characterization of all intermediates throughout the synthesis.
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