Brown’s asymmetric

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]. 

Lautens and Ma made use of Brown s asymmetric hydroboration reaction to afford optically enriched alcohol 104 in 83% ee,Eq. 78 [120,121]. 

Jennings strategy for obtaining the macrolide skeleton was Yamaguchi esterification and ring closing metathesis (RCM) with 175 and 176 (Scheme 36). Construction of the key 2,6-cis-tetrahydropyran in 176 was carried out via diastereoselective axial reduction of an oxonium cation. The precursor, a pyranone, was prepared via RCM of divinyl ester 177. An asymmetric center was made by Brown s asymmetric allylation. 

The synthesis of 252 began with Brown s asymmetric crotylation to aldehyde 261. The resulting homoallyl alcohol was converted benzyl ester 262, which was reduced to give lactol acetate 263. Axial allylation to 263 formed 2,6-trans-tetrahydropyran 264, which was subjected to ozonolysis to give an aldehyde. Addition of alkenylzinc, prepared by hydrozircona-tion of an alkyne 265, to the aldehyde mediated by chiral ligand 266 yielded allyl alcohol 267 with a 5.1 1 diastereoselectivity [110]. The stereochemistry of the major isomer was found, unexpectedly, to be the S-form at Cl7, which rendered the macrolactonization to adopt the Mitsunobu reaction. The iodide 252, prepared from 267 in three steps, reacted with... 

O PMP Brown s asymmetric allylaUon Homer-Emmons reaction... 

The C29-C34 fragment, trans vinyl iodide 159, is distinguished by two contiguous stereogenic centers, and it was surmised that both could be introduced in a single step through the application of Brown s effective asymmetric crotylboration methodology (see Scheme 48).79 Depro-... 

Although the asymmetric hydrogenation of itaconic acid derivatives is a potential synthetic approach to many useful product [105], lower enantioselectivities are often reported. In contrast with other catalysts, f-Bu-BisP, Ad-BisP, t-Bu-MiniPHOS, BIPNOR 27, and Brown s ligand 25 gave high to almost perfect ees in the hydrogenation of these substrates (Scheme 23) [101]. 

Brown s synthesis of 34 and 35 utilized -2 -isoprenyldi-Z-isopinocam-pheylborane B as a reagent for asymmetric isoprenylation of aldehydes as shown in Scheme 50 [76]. 

A useful reagent for asymmetric hydroboration. See Brown s Hvdroboration Reaction. 

The control of the three consecutive asymmetric centers in a-alkylated y-amino-p-hydroxy acids is achieved by aldol condensation of a chiral aldehyde and a chiral reagent (Scheme 17 and Table 6), e.g. boron enolate 43,150 79 oxazolidinones of Evans type lit80 or 45 [68>69>801 or Brown s or Roush s crotylorganoboron reagents 46[81 and 47J81,82 respectively. 

The use of oxazaborolidines as asymmetric reduction catalysts257 and the enantioselectivity of diphcnyloxazaborolidinc reduction of ketones have been reviewed.258 Large-scale practical enantioselective reduction of prochiral ketones has been reviewed with particular emphasis on the Itsuno-Corey oxazaborolidinc and Brown s 5-chlorodiisopinocampheylborane (Ipc2BCl) as reagents.259 Brown himself has also reviewed the use of Ipc2BCl.260 Indolinoalkylboranes in the form of dimers have been confirmed by 11B NMR as the products of the reduction of trifluoroacetylindoles by diborane.261... 

Fig. 10.25. Asymmetric carbonyl group reduction with diisopinocampheylchloroborane [Brown s chloroborane, (IPC)2BCL]. Concerning the reduction product depicted in the top row, the designation 5 of the configuration relates to the aryl-substituted and R to the Rttrt-substituted propargylic alcohol.

Fig. 8.20. Asymmetric carbonyl group reduction with diisopinocampheylchloro-borane [Brown s chloroborane, (IPC)2BC1].

Using Keck s original catalytic allylation procedure, Danishefsky and co-workers converted aldehyde 474 to the homoallylic alcohol 475 (conditions A, Scheme 11-38, 60% yield, >95% ee) used in their total synthesis of epothilones A and B [314], Asymmetric allylation with a stoichiometric amount of Brown s reagent, [(-)-lpc]2BAll (195), however, was higher yielding and required a shorter reaction time (conditions B, Scheme 11-38, 83% yield, >95% ee). 

The first asymmetric synthesis to achieve >90% optical yield was Brown s hydroboration of cis alkenes with diisopinocampheylborane (IpC2BH, Figure 7.10) in 1961 [130,131], The reagent was prepared by hydroboration of a-pinene of 90% ee 2-butanol obtained from hydroboration/oxidation of cw-2-butene had an optical purity of 87%, indicating an optical yield of 90%. ci5-3-Hexene was hydroborated in -100% optical yield. Since then, simple methods for the enantiomer enrichment of lpc2BH (and IpcBH2) have been developed [132-134], and enantioselectivities have been evaluated more carefully with the purified material. For example, lpc2BH of 99% ee affords 2-butanol (from cw-2-butene) in 98% ee and 3-hexanol (from ci5-3-hexene) in 93% ee, both determined by rotation (see Table 7.6, entries 1 and 5) [132]. ... 

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