Diastereoselective intermolecular

Table6 Highly syn-diastereoselective intermolecular Rh-catalyzed hydrogenative aldol coupling of vinyl ketones through the tri-2-furylphosphine effect3...

Scheme 4 syn-Diastereoselective intermolecular hydrogen-mediated aldol coupling employing cationic Rh catalysts ligated by tri-2-furylphosphine... 

Diastereoselective intermolecular nitrile oxide—olefin cycloaddition has been used in an enantioselective synthesis of the C(7)-C(24) segment 433 of the 24-membered natural lactone, macrolactin A 434 (471, 472). Two (carbonyl)iron moieties are instrumental for the stereoselective preparation of the C(8)-C(ii) E,Z-diene and the C(i5) and C(24) sp3 stereocenters. Also it is important to note that the (carbonyl)iron complexation serves to protect the C(8)-C(ii) and C(i6)-C(i9) diene groups during the reductive hydrolysis of an isoxazoline ring. 

Scheme 12 Diastereoselective intermolecular cathodic coupling of a,/S-unsaturated esters yields 70-98%, de 0 to >95%.

Borrelidin 1 has attracted attention because it inhibits angiogenesis, and so potentially blocks tumor growth, with an IC of 0.8 nM. Retrosynthetic analysis of 1 led the investigators to the prospective intermediates 2 and 3. To assemble these two fragments, they interatively deployed the elegant enantio- and diastereoselective intermolecular reductive ester aldol condensation that they had recently developed. This transformation is exemplified by the homologation of 4 to 6 catalyzed by the enantiomerically-pure Ir complex 5. 

The bimetallic tetraene isoxazoline 64 was prepared through a highly diastereoselective intermolecular nitrile oxide-olefin cycloaddition and used as an intermediate in the synthesis of the C7-C24 segment of macrolactin A. The addition of the nitrile oxide on the less hindered face of the s-trans triene rotomer of 63 was the key to controlling the absolute configuration of the new formed stereocenter <03S2064>. 

Verdaguer, X., Vazquez, J., Fuster, G., Bernardes-Genisson, V., Greene, A. E., Moyano, A., Pericas, M. A., Riera, A. Camphor-Derived, Chelating Auxiliaries for the Highly Diastereoselective Intermolecular Pauson-Khand Reaction Experimental and Computational Studies. J. 

In 1999, Cozzi and Umani-Ronchi described a diastereoselective intermolecular pinacol coupling of aromatic and aliphatic aldehydes in the presence of a catalytic quantity of TiCl4(THF)2/Schiff base (Eq. 3.38) [60]. Manganese is employed as the stoichiometric reductant with the Cozzi/Umani-Ronchi system, zinc generally affords a lower yield of the diol. The reaction is believed to proceed via a pathway analogous to that illustrated in Fig. 3-5. The observations of Cozzi and Umani-Ronchi that the Schiff base affects reaction diastereoselectivity and increases the reaction rate bode well for studies of asymmetric variants. In an initial investigation, these workers obtained 10% ee in a reductive dimerization of benzaldehyde (Eq. 3.39). 

Recently, Lautens, Aspiotis and Colucci extended the [4+3] cycloaddition methodology to include the diastereoselective intermolecular cycloaddition between an oxyallyl cation and a chiral furan [45]. The best results were obtained employing furan 26 bearing a free hydroxyl group in the 2-position, reacting with excess 1,3-dibromopentanone in the presence of diethyl zinc. Under the optimized conditions, up to 80% yield of the crystalline oxabicyclo[3.2.1]octene 27 was obtained with a diastereoselectivity of a 19 1. The other product was the minor diastereomer 28, Eq. 17. 

Scheme 1.38 Rh-catalyzed diastereoselective intermolecular C—H bond amination reactions reported by MUller, Dodd, and Dauban.

In 2001, Tills et al. used thiazolium chloride 620 as a carbene precursor in a diastereoselective intermolecular Stetter reaction 518) between the chiral donor 621 and aldehyde 622. The 1,4-diketone 623 thus obtained was then used successfully to access roseophilin (624) (Scheme 128) 517). The promising cytotoxicity of roseophilin (624), a macrocyclic pigment isolated from Streptomyces griseoviridis 524), has attracted considerable attention resulting in a number of partial and total syntheses of this alkaloid (525), and this example demonstrates nicely how (even achiral) organocatalysts can play an important role in obtaining a complex namral product. 

Scheme 20.25). The nucleophUic enolate 93 itself was formed by a diastereoselective intermolecular O-Michael reaction of 92 with a hthium alkoxide through outside attack of the macrocychc enone. The alkoxide also served as a surrogate of the C5-hydroxy group of the natural product. The transannular Michael reaction of 93 led to stereoselective formation of the tetracyclic 94 in 73% yield. The stereoselectivity of the transannular Michael reaction was a result of the favorable conformation of the macrocycle. 

Acetal skeletons are also obtained as products through a highly regio- and diastereoselective intermolecular addition of water and alcohols to alkynyl epoxides catalyzed by gold(I) (Scheme 16) [134, 135]. 

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