Cyclopentanes chiral-substituted

An enantioselective variant of the diene cydization reaction has been developed by application of chiral zirconocene derivatives, such as Brintzinger s catalyst (12) [10]. Mori and co-workers demonstrated that substituted dial-lylbenzylamine 25 could be cyclized to pyrrolidines 26 and 27 in a 2 1 ratio using chiral complex 12 in up to 79% yield with up to 95% ee (Eq. 4) [ 17,18]. This reaction was similarly applied to 2-substituted 1,6-dienes, which provided the analogous cyclopentane derivatives in up to 99% ee with similar diastereoselectivities [19]. When cyclic, internal olefins were used, spirocyclic compounds were isolated. The enantioselection in these reactions is thought to derive from either the ate or the transmetallation step. The stereoselectivity of this reaction has been extended to the selective reaction of enantiotopic olefin compounds to form bicyclic products such as 28, in 24% yield and 59% ee after deprotection (Eq. 5) [20]. 

The first catalytic 1,4-addition of diethylzinc to 2-cyclopentenone with over 90% ee was described by Pfaltz and Escher, who used phosphite 54 with biaryl groups at the 3,3 -positions of the BINOL backbone.46 Chan and co-workers achieved high enantioselectivity in the same reaction (up to 94% ee) by using chiral copper diphosphite catalyst (R,R,R)-41 48,48a 48d Hoveyda and co-workers used ligand 46 to realize excellent enantiocontrol (97% ee) in the 1,4-additions of 2-cyclopentenones,52 which may be used in the practical asymmetric synthesis of some substituted cyclopentanes (including prostaglandins). 

Widenhoefer and co-workers have developed an effective Pd-catalyzed protocol for the asymmetric cyclization/ hydrosilylation of functionalized 1,6-dienes that employed chiral, non-racemic pyridine-oxazoline ligands." " " Optimization studies probed the effect of both the G(4) substituent of the pyridine-oxazoline ligand (Table 7, entries 1-6) and the nature of the silane (Table 7, entries 6-15) on the yield and enantioselectivity of the cyclization/ hydrosilylation of dimethyl diallylmalonate. These studies revealed that employment of isopropyl-substituted catalyst (N-N)Pd(Me)Gl [N-N = (i )-( )-4-isopropyl-2-(2-pyridinyl)-2-oxazoline] [(i )-43f and a stoichiometric amount of benzhydryldimethylsilane provided the best combination of asymmetric induction and chemical yield, giving the corresponding silylated cyclopentane in 98% yield as a single diastereomer with 93% ee (Table 7, entry 15). 

Now, let us have a look at the cyclic compounds. We can use this E) and (Z) system for a cyclic compound when two or more groups are attached to a ring. For example, if in the following substituted cyclopentane A and B are different groups, each C atom attached to A and B is a chiral carbon or stereocentre. 

Rhodium(II) acetate catalyzes C—H insertion, olefin addition, heteroatom-H insertion, and ylide formation of a-diazocarbonyls via a rhodium carbenoid species (144—147). Intramolecular cyclopentane formation via C—H insertion occurs with retention of stereochemistry (143). Chiral rhodium (TT) carboxamides catalyze enantioselective cyclopropanation and intramolecular C—N insertions of CC-diazoketones (148). Other reactions catalyzed by rhodium complexes include double-bond migration (140), hydrogenation of aromatic aldehydes and ketones to hydrocarbons (150), homologation of esters (151), carbonylation of formaldehyde (152) and amines (140), reductive carbonylation of dimethyl ether or methyl acetate to 1,1-diacetoxy ethane (153), decarbonylation of aldehydes (140), water gas shift reaction (69,154), C—C skeletal rearrangements (132,140), oxidation of olefins to ketones (155) and aldehydes (156), and oxidation of substituted anthracenes to anthraquinones (157). Rhodium-catalyzed hydrosilation of olefins, alkynes, carbonyls, alcohols, and imines is facile and may also be accomplished enantioselectively (140). Rhodium complexes are moderately active alkene and alkyne polymerization catalysts (140). In some cases polymer-supported versions of homogeneous rhodium catalysts have improved activity, compared to their homogenous counterparts. This is the case for the conversion of alkenes direcdy to alcohols under oxo conditions by rhodium—amine polymer catalysts... 

Very recently, the first catalytic asymmetric intramolecular a-alkylation of an aldehyde has been achieved by the List group [70]. In the presence of a-methyl-substituted L-proline, (S)-61, as organocatalyst, ring-forming reactions leading to chiral cyclopentanes, cyclopropanes, and pyrrolidines proceed with high enantioselectivity - in the range 86-96% ee. Selected examples are shown in Scheme... 

Chiral Cyclopentane Synthesis From Sugars Transformation of monosaccharides into enantiomerically pure penta- substituted cyclopentanes via fragmentation and nitrone-olefin dipolar cycloaddition. 

The pyrrolidine-based diphosphane possesses the same anisyl-phenyl-phosphino groups as DIPAMP (14). Two similarly substituted phosphine groups attached to the cyclopentane (15), ferrocene (16), and xanthene (17) backbone resulted in efficient P-chiral ligands too (Fig. 3). The BIPNOR ligand is unique among this class of ligands because it contains two phosphanorbomadiene units (18). 

The most recent foray into the group 3 biomimetic approach launched by Brooks, Grothaus and Mazdiyasni (27) has resulted in the first synthesis of the cytostatic agent anguidine (9). Importantly, this work also represented the first chiral synthesis of a trichothecene metabolite, as their sequence opened with an enantioselective microbial reduction (26) of dione (174) shown in Scheme 16. The fact that this reduction yielded the unnatural configuration at the carbon destined to be C-4 in the trichothecene skeleton is easily rectified by an alcohol inversion sequence furnishing, after suitable protection, the optically pure cyclopentane (175). Further elaboration of this chiral synthon, as reported in a preliminary communication 28), led to the heavily substituted oxabicyclo[3.2.1]octane (176). 

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