Ephedrine-borane

The dilithium salt of a chiral diaminodiol derived from ephedrine mediates the enantioselective addition of dialkylzinc to aldehydes to afford (f )-l-phenylethanol with 85% ee (eq 19).  

Takahashi, H. Tomita, K. Noguchi, H. Chem. Pharm. Bull. 1981, 29, 3387. 

Mukaiyama, X Fujimoto, K. Hirose, X. Takeda, X Chem. Lett. 1980, 635. 

Yokoyama, S. Hayasaka, X Ebihara, K. Chem. Lett. 1988, 843. 

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In 1969, Fiaud and Kagan[U1 tested ephedrine boranes but achieved only 3.6-5% enantiomeric excess in the reduction of acetophenone. Itsuno et a/.[121 reported in 1981 an interesting enantioselective reduction of a ketone using an amino alcohol-borane complex as a catalyst. Buono[131 investigated and developed the reactivity of phosphorus compounds as ligands in borane complexes for asymmetric hydrogenation. 

Related Reagents. a,a-Diphenyl-2-pyrrolidinemethanol Ephedrine-borane Norephedrine-Borane Tetrahydro-l-me-thyl-3,3-diphenyl-l//,3//-pyrrolo[l,2-c][l,3,2]oxazaborole. 

Related Reagents. 2-Amino-3-methy 1-1,1-diphenyl-1-butanol Ephedrine-borane Norephedrine-Borane Tetrahydro-1-methyl-3,3-diphenyl- l/f,3/f-pyrrolo[ 1,2-c] [ 1,3,2]oxaz aborole. 

The first attempt to use a chiral ligand to modify borane was Kagan s attempt at enantioselective reduction of acetophenone using amphetamine-borane and desoxy-ephedrine-borane in 1969 [18]. However, both reagents afforded 1-phenyl ethanol in <5% ee. The most successful borane-derived reagents are oxazaborolidines, introduced by Hirao in 1981, developed by Itsuno, and further developed by Corey several years later (reviews [19,20]). Figure 7.2 illustrates several of the Hirao-Itsuno and Corey oxazaborolidines that have been evaluated to date. All of these examples are derived from amino acids by reduction or Grignard addition. Hirao... 

Jug6 S (2008) Enantioselective synthesis of P-chirogenic phosphorus compounds via the ephedrine-borane complex methodology. Phosphorus Sulfur Silicon 183 233-248... 

The oxazaborolidines are easily prepared by heating ephedrine with borane dimethyl sulfide or the appropriate boronate ester. The aluminum reagent C is obtained by mixing ephedrine and trimethylaluminum. Borolidinc A is superior to its methyl derivative B and to the aluminum analog C. The diastereomeric borolidine obtained from borane and (S,S)-pseu-doephedrine failed to show any cnantioselectivity25. A variety of aromatic aldehydes can be enantioselectively alkylated in the presence of A, however, with heptanal the enantioselectivity is poor25. 

Despite the high sensitivity of the methods for chiral resolution described in Section IV.D.4, more direct methods are afforded by NMR spectroscopy, especially for the products of synthesis. Ephedrine (179), pseudoephedrine (180a) and its Me ether (180b) yield stable epimeric N — BH3 adducts on treatment with borane. The configuration of the nitrogen moiety was established by NMR, taking into account the conformational analysis of the molecule392. 

Rh-H / -elimination step in step E gives the vinyl-borane which then dissociates to generate the first intermediate. This cycle explains the production of equimolar quantities of alkane and -vinylborane with unreactive R2BH derived from ephedrines with catecholborane there is an additional shunt pathway — step C in competition with step E leading to the primary regio-isomer of alkylborane. 

Various prochiral olefins are hydroborated by Rh complexes of BINAP or DIOP in up to 96% optical yield (30h, 31). Oxidation of the products provides a convenient way to produce optically active alcohols. Reaction of styrene and catecholborane in the presence of a BINAP-Rh complex at low temperature forms, after oxidative workup, 1-phenylethyl alcohol in 96% ee (Scheme 11) (31). Double stereodifferentiation occurs in the BINAP-Rh catalyzed reaction of 4-methoxy-styrene and an ephedrine-derived chiral borane (32). 

Other routes to A .A -DIPAMP (2) have been reported.2 31 At present, the most practical synthesis of DIPAMP involves the formation of a single diastereoisomer of 18 by the combination of PhP(NEt2) 2 and (-)-ephedrine followed by formation of the borane adduct (Scheme 12.3).29,32,33... 

Preparative Methods a solution of (l/ ,2S)-(—)-ephedrine (8.25 g, 50 mmol) in anhydrous THF (50 ml) was treated with Borane-Dimethyl Sulfide complex (50 mmol, 5 mL of 10 M solution). The reaction mixture was stirred at 25 °C for 1 h, at which time one equivalent of hydrogen had evolved. The volatiles were removed in vacuo to furnish a white solid, B NMR (3 8 ppm). The solid was gradually heated to 100 °C and maintained at that temperature until the second equivalent of hydrogen had evolved. The product was distilled under reduced pressure to provide the pure oxazaborolidine (86%). An alternative procedure is available. ... 

Boranes other than those based on a-pinene are particularly useful in allylic transfer to imines to make single enantiomers of unsaturated amines. One good combination is an allylboron compound 80 complexed with an /V-sulfonyl amino alcohol such as 78, derived from nor-ephedrine (see chapter 23) with an /V-silyl imine such as 81. The unsaturated amines 82 are formed in good... 

Juge developed a powerful method (Juge-Stephan method) [1, 51] for the preparation of / -stereogenic phosphines based on the use of ephedrine as a chiral auxiliary. The key reactants in this methodology are 1,3,2-oxazaphospholidine boranes 78, prepared by a one-pot reaction from bis(diethylamino)phenylphosphine and (—)-ephedrine, followed by protection with BH3. The cyclization of the (—)-ephedrine takes place stereoselectively, with preferential formation of the (/ p)-diastereoisomer in 90% de [52, 53]. The absolute configuration at the phosphorus atom has been determined by chemical correlations and NMR analysis, and proved by X-ray analysis [54]. Oxazaphospholidines react readily with electrophiles or nucleophiles to provide various chiral phosphorus compounds. Enantiomeric antipodes of tertiary phosphines (Sp)-79 and (Rp)-81 were obtained from (-1-)- or (-)-ephedrine, as shown in Scheme 25. The configuration at the E-atom is controlled by the configuration at the Ph-substituted Cj of (-i-)-pseudoephedrine or ( )-ephedrine, respectively. This was confirmed by X-ray crystal-structure analyses of two intermediate compounds in the synthetic route to the chiral triarylborane-phosphine adducts [54]. 

The stereoselective synthesis of the (RJi)- (or (S,S)-ligands) 99 was performed in several steps using the ephedrine methodology with (-t)- or (—)-ephedrine, respectively. The key step of the synthesis is the methano bridge formation by reaction of the carbanion derived methyl phosphine borane 98 with the chloro... 

Norbornenes, 2,3-disubst. 38, 850s44 (-)-Norephedrine s.a. Borane-(-)-nor-ephedrine... 

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