C2-symmetrical 1,4-diols

D-Mannitol (63) has been used for the synthesis of y-butyrolactones, making again use of a Claisen rearrangement as the key step (Scheme 10). The C2-symmetrical 1,4-diol 65, obtained from 63 via the alkene 64 [28], could be converted to 67 by applying the Eschenmoser-Claisen variant. Cyclization to 68 was readily achieved upon heating 67 in xylene, establishing two differ-... 

For the synthesis of C2-symmetric 1,4-diol, Evans planned temporary silicon-tethered ring-closing metathesis, and asymmetric synthesis of D-altritol was... 

This enantioselective preparation of allylic alcohols has been applied to the synthesis of the side chain of prostaglandins . The addition to functionalized aldehydes, such as 483, allows the synthesis of C2-symmetrical 1,4-diols, such as 484, with excellent diastereoselectivity and enantioselectivity . An extension of this method allows the synthesis of C3-symmetrical dioF . Aldol-type products result from the catalytic enantioselective addition of functionalized dialkylzincs to 3-TIPSO-substituted aldehydes, such as 485, followed by a protection-deprotection and oxidation sequence affording 486 in 70% yield and 91% ee (Scheme 118) . The addition to a-alkoxyaldehydes provides a... 

Reduction of 1,4-Diketones. Synthetic access to C2-symmetric 1,4-diols, useful building blocks for the preparation of chiral 2,5-disubstituted pyrrolidines and phospholanes, involves reduction of the parent 2-alkane-1,4-diones, or, even better, reduction of the related ( )-alk-2-ene-1,4-diones (11) (eq 7) or 2-alkyne-1,4-diones (12) (eq 8), followed by catalytic hydrogenation. ... 

Clarke, P. A. Selective monoacylation of meso-and C2-symmetric 1,3- and 1,4-diols. Tetrahedron Lett. 2002, 43, 4761 1763. 

C2-Symmetric chiral 1,4-diols can be prepared by the oxazaborolidine-cata-lyzed reduction of 2-ene-l,4-diones and 2-yne-l,4-diones [93]. From ferrocenyl diketones, the corresponding C2-symmetrical chiral diols were prepared in high ees (>98% ee) [94]. Enantiopure (>99% ee) (S, S)-l,2-diarylethanediols were also synthesized by borane reduction of diaryl 1,2-diones using 4a [95]. 

The C2-symmetric bis( phospholancs) (3 and 4) can be prepared by reaction of a dilithium bis(phosphido)cthane (I) with the cyclic sulfate (2) of chiral 1,4-diols. 

Many phospholanes have been prepared by reaction of primary phosphines with imiesylates or cyclic sulfates derived from 1,4-diols. " When the diol is not C2-symmetric, P-stereogenic phospholanes result, which are discussed here. 

The reaction of monodeprotonated [ C2]acetylene with carbonyl compounds has been exploited as a means of extension of the carbon chain of various terpenes and steroids by two [ " C]carbon atoms. In the simplest case, reaction of potassium [ C2]acetylide with steroid ketone 1 and subsequent acid catalyzed cleavage of the enol ether protecting group gave 17a-[ C2]ethynyltestosterone (2). The sequential addition of deprotonated [ C2]acetylene to carbonyl compounds opens access to symmetrical or unsymmetrical [2,3- C2]alkyn-l,4-diols is exemplified in the synthesis of all-tran -/3-[15,15 - C2]-carotene ([ C2]provitamin A). Thus, treatment of lithium [ C2]acetylide with terpene aldehyde 2 followed by double deprotonation of the resultant alkynol 4 and reaction with a second equivalent of 3 provided alkyne-l,4-diol 5 the requisite key intermediate. Subsequent acid-catalyzed dehydration of 5 followed by Lindlar s catalyst-mediated partial hydrogenation and photoisomerization afforded the final product". ... 

However, most asymmetric 1,3-dipolar cycloaddition reactions of nitrile oxides with alkenes are carried out without Lewis acids as catalysts using either chiral alkenes or chiral auxiliary compounds (with achiral alkenes). Diverse chiral alkenes are in use, such as camphor-derived chiral N-acryloylhydrazide (195), C2-symmetric l,3-diacryloyl-2,2-dimethyl-4,5-diphenylimidazolidine, chiral 3-acryloyl-2,2-dimethyl-4-phenyloxazolidine (196, 197), sugar-based ethenyl ethers (198), acrylic esters (199, 200), C-bonded vinyl-substituted sugar (201), chirally modified vinylboronic ester derived from D-( + )-mannitol (202), (l/ )-menthyl vinyl ether (203), chiral derivatives of vinylacetic acid (204), ( )-l-ethoxy-3-fluoroalkyl-3-hydroxy-4-(4-methylphenylsulfinyl)but-1 -enes (205), enantiopure Y-oxygenated-a,P-unsaturated phenyl sulfones (206), chiral (a-oxyallyl)silanes (207), and (S )-but-3-ene-1,2-diol derivatives (208). As a chiral auxiliary, diisopropyl (i ,i )-tartrate (209, 210) has been very popular. 

The use of tartrate esters was an obvious place to start, especially since both enantiomers are readily available commercially and had already found widespread application in asymmetric synthesis (Figure 11) (e.g.. Sharpless asymmetric epoxidation).23.24 Reagents 36-38 are easily prepared and are reasonably enantioselective in reactions with achiral, unhindered aliphatic aldehydes (82-86% ee) typical results are given in Figure 12.3c,h Aromatic and a,p-unsaturated aldehydes, unfortunately, give lower levels of enantioselection (55-70% e.e.). It is also interesting to note that all other C2 symmetric diols that we have examined (2,3-butanediol, 2,4-pentanediol, 1,2-diisopropylethanediol, hydrobenzoin, and mannitol diacetonide, among others) are relatively ineffective in comparison to the tartrate esters (see Table ll).25... 

Another method for the asymmetric version of the Baeyer-Villiger reaction was presented by Lopp and coworkers in 1996 . By employing overstoichiometric quantities of Ti(OPr-t)4/DET/TBHP (1.5 eq./1.8 eq./1.5 eq.), racemic andprochiral cyclobutanones were converted to enantiomerically enriched lactones with ee values up to 75% and moderate conversions up to 40% (Scheme 171). Bolm and Beckmann used a combination of axially chiral C2-symmetric diols of the BINOL type as ligands in the zirconium-mediated Baeyer-Villiger reaction of cyclobutanone derivatives in the presence of TBHP (or CHP) as oxidant (Scheme 172) . With the in situ formed catalysts 233a-d the regioisomeric lactones were produced with moderate asymmetric inductions (6-84%). The main drawback of this method is the need of stoichiometric amounts of zirconium catalyst. 

A combination of axially chiral C2-symmetric binaphthol 85 with Zr(OBu-f)4 and TBHP represented a novel access to asymmetric BV oxidation. The system works under stoichiometric conditions and leads to the formation of the zirconium species 113, responsible for the activation of ketone and, likely, of the peroxide . As an example, the BV oxidation of 114 afforded the lactones 115 and 116 in a ratio 1 5 with 84% and 14% ee, respectively (equation 80). Asymmetric inductions are preserved also if one of the two chiral diols coordinated to zirconium is replaced with conformationally flexible biphenols . 

Lewis acid-promoted asymmetric addition of dialkylzincs to aldehydes is also an acceptable procedure for the preparation of chiral secondary alcohol. Various chiral titanium complexes are highly enantioselective catalysts [4]. C2-Symmet-ric disulfonamide, chiral diol (TADDOL) derived from tartaric acid, and chiral thiophosphoramidate are efficient chiral ligands. C2-Symmetric chiral diol 10, readily prepared from 1-indene by Brown s asymmetric hydroboration, is also a good chiral source (Scheme 2) [17], Even a simple a-hydroxycarboxylic acid 11 can achieve a good enantioselectivity [18]. 

Introduction. (l/ ,5i -2//-l,5-Benzodithiepin-3(4/ -one 1,5-dioxide (C2-symmetric his-sulfoxide 1) has been used as a chiral auxiliary for asymmetric desymmetrization of cyclic meso-1,2-diols via diastereoselective acetal cleavage reaction. The procedure consists of three steps (eq 1), that is, acetalization (step 1), acetal cleavage reaction followed by benzylation (step 2), and hydrolysis of the vinyl ether (step 3). Due to the Ca-symmetry of 1, the chiral auxiliary gives only one product in step 1. In addition, no regio- or geometric isomers of the enol ether are formed in step 2. This reagent can be recovered by acid-promoted hydrolysis and reused. 

Using a strategy similar to the asymmetric acylation described above (4.1.1), the symmetrical 2,5-dibenzoate 172 was transformed to the optically pure diol 174 in 70% yield with complete enantioselectivity by the reaction of one pair of the two enantiotopic vicinal diols with the novel chiral pyranyl pyran 173 with a C2 axis in the presence of camphorsul f onic acid (CSA) (Scheme 4-3). 72 This unique spiroketal, which is named dispoke... 

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