Stereoselectivity preparations

Because the Corey synthesis has been extensively used in prostaglandin research, improvements on the various steps in the procedure have been made. These variations include improved procedures for the preparation of norbomenone (24), alternative methods for the resolution of acid (26), stereoselective preparations of (26), improved procedures for the deiodination of iodolactone (27), alternative methods for the synthesis of Corey aldehyde (29) or its equivalent, and improved procedures for the stereoselective reduction of enone (30) (108—168). For example, a catalytic enantioselective Diels-Alder reaction has been used in a highly efficient synthesis of key intermediate (24) in 92% ee (169). 

Since this original synthesis, a great number of improvements (191—201) have been made in the stereoselective preparation and derivatization of the CO-chain precursor, in cuprate reagent composition and preparation, in protecting group utilization, and in the preparation and resolution of hydroxycyclopentenones. Illustration of some of the many improvements are seen in a synthesis (202) of enisoprost, a PGE analogue. The improvements consist of a much more efficient route to the enone as well as modifications in the cuprate reactions. Preparation of the racemic enone is as follows ... 

This reaction illustrates a stereoselective preparation of (Z)-vinylic cuprates, which are very useful synthetic intermediates. They react with a variety of electrophiles such as carbon dioxide, epoxides, aldehydes, allylic halides, alkyl halides, and acetylenic halides they undergo... 

Stereoselective Preparation of Tnfluoro-melhy/ated Organic Molecules Yamazdki.T Kitazume T Rev Heteroat Chem 7 132-148 48... 

Stereoselective preparation of CEi-allyl alcohols via radical elimination from ruin -y-phenylthio-fi-nkro alcohols has been reported. The requisiteruin -fi-nitro sulfides are prepared by protonadon of nitronates at low temperanire Isee Chapter 4, and subsequent treatment v/ith Bu-vSnH induces and eliminadon to givelE -alkenes selecdvely IseeEq. 7.112. Unfortunately, it is difficult to get the pure syu-fi-nitro sulfides. Treatment of a rruxnire of syu- and ruin -fi-nitrosulfides v/ith Bu- SnH results in formadon of a rruxnire of (Ey and lZ -alkenes. 

Stereoselective preparations of 1,3-dienes are described in References 219 and 224 and the preparation of (-l-)-aspicillin in Reference 225. 

Using FmA catalysis and protected 4-hydroxybutanal, compound (97) has been stereoselectively prepared as a synthetic equivalent to the C-3-C-9 fragment of (-F)-aspicillin, a lichen macrolactone (Figure 10.35) [160]. Similarly, FruA mediated stereoselective addition of (25) to a suitably crafted aldehyde precursor (98) served as the key step in the synthesis of the noncarbohydrate , skipped polyol C-9-C-16 chain fragment (99) of the macrolide antibiotic pentamycin [161,162]. 

Chiral-at-metal cations can themselves serve as chirality inducers. For example, optically pure Ru[(bipy)3] proved to be an excellent chiral auxihary for the stereoselective preparation of optically active 3D anionic networks [M(II)Cr(III)(oxalate)3]- n (with M = Mn, Ni), which display interesting magnetic properties. In these networks all of the metalhc centers have the same configuration, z or yl, as the template cation, as shown by CD spectroscopy and X-ray crystallography [43]. 

The hydroxynitrile lyase (HNL)-catalyzed addition of HCN to aldehydes is the most important synthesis of non-racemic cyanohydrins. Since now not only (f )-PaHNL from almonds is available in unlimited amounts, but the recombinant (S)-HNLs from cassava (MeHNL) and rubber tree (HbHNL) are also available in giga units, the large-scale productions of non-racemic cyanohydrins have become possible. The synthetic potential of chiral cyanohydrins for the stereoselective preparation of biologically active compounds has been developed during the last 15 years. 

Amino alcohols, which have a broad spectrum of biological activities, can be categorized as adrenahne-like with one chiral center at C-1 or as ephedrine-like with two chiral centers at C-1 and C-2 (Scheme 7). Although a variety of methods have been developed for the stereoselective preparation of 1,2-amino alcohols, " in most cases it is easier and more efficient to prepare these important compounds stereoselectively starting from chiral cyanohydrins (Scheme... 

The anti elimination can also be achieved by converting the (3-silyl alcohols to trifluo-roacetate esters.273 The stereoselectivity of the Peterson olefination depends on the generation of pure syn or anti P-silylalcohols, so several strategies have been developed for their stereoselective preparation.274... 

An experimentally simple procedure for stereoselectively preparing P-nitro alcohols has been developed. The alkyl nitronates, formed by the action of n-butyllithium on nitroalkanes in THF solution, react with aldehydes in the presence of isopropoxytitanium trichloride at room temperature to give the P-nitro alcohols enriched in the anri-diastereoisomers (Eq. 3.71).112... 

An alternative method for the stereoselective preparation of 1,2-diamines is shown in Eq. 4.29, in which the addition of nitroalkanes to imines is used as a key reaction.35... 

Stereoselective preparation of ( )-allyl alcohols via radical elimination from anti-j-phenylthio-P-nitro alcohols has been reported.154 The requisite anti-P-nitro sulfides are prepared by protonation of nitronates at low temperature (see Chapter 4), and subsequent treatment with Bu3SnH induces anti elimination to give (E)-alkenes selectively (see Eq. 7.112). Unfortunately, it is difficult to get the pure yyw-P-nitro sulfides. Treatment of a mixture of syn- and anti-P-nitrosulfides with Bu3SnH results in formation of a mixture of (E)- and (Z)-alkenes. 

Nitroalkenes with Chiral Auxiliaries The use of carbohydrates as chiral auxiliary in Diels-Alder reactions for the stereoselective preparation of carbocyclic and heterocyclic chiral rings is well documented.48 For example, D-manno-nitroalkene reacts with 2,3-dimethyl-1,3-butadiene to give a 65 35 mixture of adducts, as shown in Eq. 8.29. The configurations at C-4 and C-5 have been determined to be (4R,5R) and (45,55), respectively. Hydrolysis of the product followed by degradative oxidation of the sugar side chains leads to enantiomerically... 

Acylbenzotriazoles 162 are efficient C-acylation reagents for the regioselective conversion of ketone enolates into P-diketones . Diethyl(l-benzotriazolmethyl)phosphinate (163) was found to be a convenient reagent for the stereoselective preparation of (E)-l-(l-alkenyl)benzotriazoles <00SC1413>. The novel three-carbon synthon 1-(1//-133-... 

A new procedure for the stereoselective preparation of cis-3-hydroxy-2-ethynyl oxepane derivatives, exemplified by 43, based on 5,6-epoxy-7-octyn-l-ols via endn cyclization mediated by Co2(CO)a has been described. The procedure is not stereospecific however . 

Haynes, R.K., Lam, W.W.-L., and Yeung, L.-L., Stereoselective preparation of functionalized tertiary P-chiral phosphine oxides by nucleophilic addition of lithiated tert-butylphenylphosphine oxide to carbonyl compounds, Tetrahedron Lett., 37, 4729, 1996. 

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. 

The intermolecular ruthenium enyne Alder-ene reaction has been extended to the stereoselective preparation of enamines (Equation (26)).39 The yields obtained for this reaction were high with allylacetamides, -benzamides,... 

The acyl anion chemistry of acylzirconocene chlorides has also been applied to the stereoselective preparation of ( )-a,(3-unsaturated selenoesters and telluroesters (Scheme 5.35) [38]. Although no carbon—carbon bond was formed, this reaction reflects the synthetic interest in ( )-a,(3-unsaturated selenoesters and telluroesters, which are well-known precursors of acyl radicals and acyl anions, respectively. 

An interesting application of the cydization of alkenyl thioacetals is the stereoselective preparation of olefmic diols. Thus, oxidative cleavage of the silicon—carbon bond [32] in the ring-closed metathesis products, i.e. cyclic allylsilanes such as 35 and 36, affords (Z)-alk-2-ene-1,5-diols 37 and 38 (Scheme 14.18) [33],... 

Scheme 14.34. Stereoselective preparation of conjugated dienes by the titanocene(ll)-promoted reaction of thioacetals with alkynes.

Following the discovery of a bulk fullerene preparation process in 1990, the covalent chemistry of these carbon allotropes has developed at a phenomenal pace. Frontier orbital (LUMO) and tether-directed functionalization concepts have been successfully applied to the regio- and stereoselective preparation of multiple covalent adducts of C60. These have found increasing applications in the construction of functional supramol-ecules. More recently, the sequence of Bingel reaction - retro-Bingel reaction has provided an elegant access to isomerically pure higher fullerenes and, in particular, to pure carbon enantiomers. 

Figure 13. a) General synthetic protocol for the regio- and stereoselective preparation of Ws(cyclopropanated) C6o... 

Bromolactamization (11, 76). This reaction can be used for stereoselective preparation of 3,4-disubstituted 3-lactams.1 Thus the P,-y-unsaturated hydroxamic acid 1, prepared in several steps from tiglic acid, on reaction with bromine and K2C03 in aqueous CH,CN cyclizes mainly to a rrans-p-lactam (2). In contrast, the protected a-amino-p,y-unsaturated hydroxamic acid 3, prepared in several steps from L-methionine, cyclizes on reaction with bromine mainly to a ris-p-lactam (4). 

Access to P-mannosides [209] is illustrated by the preparation of 179 from P-glucoside 178 by oxidation of the equatorial 2-OH followed by stereoselective reduction to give the axial alcohol an efficient indirect route to the a-mannosides [206] utilizes the P-thioglucoside 182, readily obtained from epoxide 173, proceeding via an oxidation-reduction protection sequence to give P-thiomannoside glycosyl donor 184, from which a-mannoside 185 can be stereoselectively prepared. 

Deoxy-a-D-ribosyl-l-phosphate 20, a key substrate in the preparation of 2 -deoxynucleosides, was stereoselectively prepared by crystallization-induced asymmetric transformation in the presence of an excess of ortho-phosphoric acid and tri( -butyl)amine under strictly anhydrous conditions (Scheme 2).7 Initial Sn2 displacement of Cl in ot-glycosyl chloride 16 by phosphoric acid resulted in a 1 1 a/p anomeric mixture of 17 and 18 due to the rapid anomerisation of the a-chloride in polar solvents. Under acidic conditions, in the presence of an excess of H3P04, an equilibration between the a and p anomers gradually changed in favour of the thermodynamically more stable a-counterpart. By selective crystallization of the mono tri( -butyl)ammonium salt of the a-phosphate from the mixture, the equilibrium could be shifted towards the desired a-D-ribosyl phosphate 18 (oc/p = 98.5 1.5), which was isolated as bis-cyclohexylammonium salt 19 and deprotected to furnish compound 20. 

In a similar way glycosyl diphenyl phosphates have been used in the stereoselective preparation of glycosyl azides on SN2-typc displacement of the phosphate group by sodium azide.27... 

Scheme 16.73 Stereoselective preparation of cyclic cross-conjugated trienes.

The procedure described here illustrates a general and inexpensive two-step method for the stereoselective preparation of new, variously substituted I-CF3 epoxy ethers from ethyl trifluoroacetate.2-3.4 The first step of this procedure is a Wittig olefination of ethyl trifluoroacetate in which sodium hydride is used for the generation... 

A method for highly efficient asymmetric cyclopropanation with control of both relative and absolute stereochemistry uses vinyldiazomethanes and inexpensive a-hydroxy esters as chiral auxiliaries263. This method was also applied for stereoselective preparation of dihydroazulenes. A further improvement of this approach involves an enantioselective construction of seven-membered carbocycles (540) by incorporating an initial asymmetric cyclopropanation step into the tandem cyclopropanation-Cope rearrangement process using rhodium(II)-(5 )-N-[p-(tert-butyl)phenylsulfonyl]prolinate [RhjtS — TBSP)4] 539 as a chiral catalyst (equation 212)264. 

Stereoelectronic effects can be invoked for the radical reaction at anomeric centre of carbohydrates. The high stereoselective preparation of a-substituted C-glycosyl phosphonates in a a p ratio of 98 2 was achieved by reductive addition of bromide 2 to a-phosphonoacrylate (Reaction 7.5) [10]. Yields (in parentheses) depend on the sugar configuration D-galacto (80%), D-manno (47 %), D-gluco (30 %) and L-fuco (62 %). 

---