Stereoselective access

The Henry reactions of A, ALdibenzyl-L-phenylalaninal with nitroalkanes using 1.2 equiv of tetrabutylammonium fluoride (TBAF) as the catalyst proceed in ahighly stereoselective manner, as shown in Eqs. 3.82 and 3.83. This reaction provides rapid and stereoselective access to important molecules containing 1,3-diamino-2-hydroxypropyl segments, which are cenhal structural subunit of the HIV protease inhibitor amprenavir (in Scheme 3.21). 

A new method of stabilizing metalated epoxides through remote coordination has recently been introduced, allowing stereoselective access to a range of epoxylactones. Epoxylactone 216 was converted into the phytotoxin xylobovide (Scheme 5.50) [75]... 

In conclusion, the use of glycosylamincs as chiral templates in the Ugi reaction provides an efficient and highly stereoselective access to both l- and D-amino acids. 

Thus, our radical tandem reactions offer highly stereoselective access to tri- and tetrasubstituted alkenes that are otherwise difficult to prepare. 

This synthesis of (-)-swainsonine involves 21 steps and proceeds with an overall yield of 6.6% from tran5-l,4-dichloro-2-butene. It is not only the first reported noncarbohydrate route to this natural product, but it allows the stereoselective access to all 16 epimers and/or enantiomers of swainsonine as well. 

Since ketone R)-16 was prepared in a non-selective way when an achiral imino enolate was alkylated, it was considered whether alkylation of chiral enolates, such as that of oxazoline 18, with benzyl bromide 14, would provide stereoselective access to the corresponding alkylation product 19 with R-configuration at C(8) (Scheme 4). Indeed, alkylation of 18 with 14 gave the biaryl 19 and its diastereoisomer almost quantitatively, in a 14 1 ratio. However, reductive hydrolysis using the sequence 1. MeOTf, 2. NaBH4, and 3. H30", afforded hydroxy aldehyde 20 in 25% yield at best. Furthermore, partial epimerization at C(8) occurred (dr 7.7 1). An alternative route, using chiral hydrazones, was even less successful. 

Habib-Zahmani H, Hacini S, Charormet E, Rodriguez J (2002) A new multicomponent domino transformation of 1,3-dicarbonyl compounds one-pot regio-, chemo- and stereoselective access to valuable alpha,gamma-difunctionalized alpha-ketoesters and amides. Synlett 1827-1830... 

A. A. Ghini, C. Bumouf, J. C. Lopez, A. Olesker, and G. Lukacs, Intramolecular Diels-Alder reactions on pyranose trienes. Stereoselective access to bis-annulated pyranosides. Tetrahedron Lett. 37 2301 (1990). 

Chemla, F. Bernard, N. Normant, J.-F. Meta-lation of 3-trimethylsilyl propargyl chloride a stereoselective access to troras-propargylic oxi-ranes. Tetrahedron Lett. 1999, 40, 75-78. 

This methodology opens up an efficient stereoselective access to chiral piperidi-none derivatives 60 which have opposite configuration compared to compounds 46 obtained by the tandem Mannich-Michael reaction sequence described in Section 4.3.2. The high diasteroselectivity and regioselectivity in these reactions once again illustrate the stereodifferentiating potential of carbohydrates in the synthesis of chiral heterocyclic systems. 

Landais, Y. Desymmetrisation of Dienylsilanes. Stereoselective Access to Cyclitols and Carba-Sugars. 1998 [92]... 

Utilization of a selenium-initiated electrophilic cyclization (lactonization, etherification) in conjunction with a [2,3] sigmatropic selenoxide rearrangement provided a convenient, stereoselective access to highly substituted bicyclic lactones or ethers (entries 6-8)25-29. The electrophilic addition of phenylselenenyl halogenides to dienes can occur in a 1,2-(anti)-or 1,4-fashion furnishing allylic selenides in both cases. 

Boschetti, A, Nicotra, F, Panza, L, Russo, G, Vinylation-electrophihc cyclization of aldopentoses easy and stereoselective access to C-glycopyranosides of rare sugars, J. Org. Chem., 53,4181-4185, 1988. 

Scheme 7-62 Stereoselective access to substituted tetrahydrofurans and pyrrolidines.

A route to ( , )-2,4-alkadienoic esters involves the Johnson-Claisen rearrangement of y-hydroxy-a,P-unsaturated sulfones and subsequent elimination of PhSO H with DBU. Stereoselective access to trisubstituted enol ethers initiated by iodoalkoxylation of disubstituted alkenes (with PyjIBF, 2HBF, ROH) is concluded by treatment with DBU.5... 

Alternatively, cyclopropanone aminals are used as starting materials leading to aminocyclopropanecarbonitriles 2 by the reaction with hydrocyanic acid. The cis or trans configuration of the bicyclic system remains unchanged in this substitution. An unexpected, highly stereoselective access to both diastereomers of 6-amino-3-azabicyclo[3.1.0]hexane-6-carbo-... 

Stereoselective access to the basic skeleton of phyllocladane-type diterpencs is also possible via cocyclotrimerization of diynes. This is achieved upon conversion of a diyne containing a methylenecyclopentane unit in the side chain with l,2-bis(tiimethylsilyl)ethyne, and a subsequent cascade consisting of benzocyclobutene ring opening and an intramolecular Diels-Alder reaction44. 

Stereoselective access to 1,6-diol derivatives from siloxanes bearing two unsaturated carbon chains is shown to be amenable to asymmetric induction. This achievement has profound implications to the synthesis of certain insect pheromones. 

Case Study (+)-Estrone 24. The Dane-style estrone synthesis provides a classic example of stereoselective access to an envisaged target molecule. The Diels-Alder reactions between 14 and 15a or 19a are chirogenic71 reaction steps or, put another way, the enantioselective access to the Diels-Alder adducts can already be set at this stage. This requires, for example, the participation of a nonracemic Lewis acid with the right sense of chirality. In the presence of a Ti-TADDOLate [42], cycloadduct 20a was thus obtained from the Dane diene 14 and the bidentate dienophile 19a and was further transformed via 23 into (+)-estrone 248) [33d]. 

Diels-Alder cycloaddition of the dienylic boronic acid 86 provided stereoselective access to the tetracyclic and tricyclic heterocycles 87 (de > 13 1) and 88 (de >20 1) (Scheme 8) <2002AGE152>. 

Likewise, the reaction of PhINTs with sulfoxides 667 in the presence of catalytic amounts of copper(I) triflate affords the corresponding (V-tosylsulfoximides 668 in high yield (Scheme 3.268) [835]. The imidation of enantiomerically pure sulfoxides 667 allows stereoselective access to iV-tosylsulfoximides 668 with complete retention of configuration at sulfur. A similar imidation procedure has been used for the preparation of chiral ferrocenylsulfoximides [838,839]. 

---