B-Chlorodiisopinocampheylborane

The simple steric model for the transition state may be used to predict the absolute configuration of the product. The related reagent (+)-B-Chlorodiisopinocampheylborane reduces ketones with greater ease and efficiency (eq 12). ... 

Treatment of 6.6 equivalents of the corresponding boron enolate of 6, [prepared by treatment of 6 with (+)-B-chlorodiisopinocampheylborane (DIP-Cl), 63, and triethylamine in diethyl ether at 0 °C], followed by aldol addition with cw-a,p-unsaturated aldehyde 8 at -78 °C, led to alcohol 64a in 50-55% yield after chromatography on reverse-phase silica gel, together with its epimer 64b in a ratio of 4 1 (Scheme 10). 

Figure 15. Stereoselective synthesis of MK-0287. Reagents a, B-chlorodiisopinocampheylborane, THF b, NaOH, MeOH, then pyridinium tosylate, toluene c, (HOCH2CH2S)2, Cu, DMF d, Mg monoper-oxyphthalate, MeCN, H20 e, TBSC1, imidazole, DMF f, DIB AL-H, toluene g, 3,4,5-trimethoxyphenyl magnesium bromide, THF h, (COOH)2, MeOH, H20.

It is worth mentioning that when B-chlorodiisopinocampheylborane was used as a stoichiometric chiral reducing agent to convert 61 into 63, the latter was obtained in a slightly lower e.e. (88%) than that observed in the catalytic reaction [69]. 

In the context of finding out efficient syntheses of enantiomerically pure multifunctional molecules containing a chiral quaternary carbon atom. Brown reported the KR of representative a-alkyl-P-ketoesters and a-tertiary ketones with B-chlorodiisopinocampheylborane (DlPCl), with the simultaneous preparation of the alcohols with de and ee >90% [67]. As an example, reduction of the Dieckmann ester 89 with O.SOMequiv of (—)-DlPCl at room temperature for 2h afforded, after the usual diethanolamine work-up, the recovered ketone (R)-89 in 43% yield (90% ee). A 37% yield of the methyl l-methyl-2-hydroxycyclopentanecarboxylates 90 with a cis trans ratio 3 97 was reported. The (IS, 2S)-trans-isomer showed 96% ee. Increasing the ratio reagent substrate improved the efficiency of the KR of the ketone, at the expense of the diastereomeric excess and enantiomeric excess of the... 

An improvement of this strategy has been realized with the use of (—)-B-chlorodiisopinocampheylborane 58 as chiral additive. In this case, a kinetic resolution is used to reduce one of the two carbonyl groups of racemic 37 with 50% conversion, which gives the enantio-enriched (—)-37 and the alcohol (+)-59 in 71% and 56% ee, respectively. The oxidation of alcohol 59 then leads to the other enantiomer (+)-37 (Scheme 25) (2004CEJ6531). 

Since the introduction of this reagent in 1983 (/2), it has been utilized in key steps in several syntheses. The reagent can be prepared by the treatment of allyl Grignard reagent with either B-chlorodiisopinocampheylborane (DIP-Chloride M) 34, 35) or B-methoxydiisopinocampheylborane 12). A variety of aldehydes, including perfluoroalkyl 36) and heterocyclic aldehydes (57) have been tested with this reagent to demonstrate its capability. In all of the cases examined thus far the product homoallyl alcohols were obtained in >92% ee (Scheme 2). It has been established that in the case of chiral aldehydes, the reagent controls the diastereoselectivity 38). 

Ramachandran, P. V, Gong, B., Brown, H. C. 1995. Chiral synthesis via organoboranes. 41. The utility of B-chlorodiisopinocampheylborane for a general s5mthesis of enantiomerically pure drugs. Chirality 1 103-110. 

Ramachandran, P. V., Pitre, S., Brown, H. C. 2002. Selective reductions. 59. Effective intramolecular asymmetric reductions of a-, P-, and y-keto acids with diisopinocampheylborane and intermolecular asymmetric reductions of the corresponding esters with B-chlorodiisopinocampheylborane. J. Org. Chem. 67 5315-5319. 

Typical experimental procedure for the preparation of B-Allyldiisopinocampheylborane 9 and its subsequent allylboration with aldehydes AUyhnagnesium bromide (1.0 mol) is added drop-wise to a stirred solution of B-chlorodiisopinocampheylborane (IPC2BCI, 25) or B-methoxydiisopinocam-pheylborane (IpC2BOMe, 26) (1.05 mol in 1 L ether) at 0 C. After the completion of the reaction as monitored by B NMR (5 79), the reaction mixture is filtered under nitrogen and concentrated under... 

Protection of Phenols. Methoxyethoxymethyl chloride can also be used to protect phenols. The conditions for its introduction are similar to those used for alcohols (NaH, THE, 0°C MeOCH2CH20CH2Cl, 0°C 25°C, 2 h, 75% yield). In contrast to the alcohol derivatives, phenolic MEM ethers can be cleaved with Trifluoroacetic Acid (CH2CI2, 23 °C, 1 h, 74% yield). 1 M HCl (THE, 5 h, 60 °C) and HBr/EtOH will also effect cleavage. In general, the cleavage conditions used for alcohols are also effective with the phenolic derivatives. During an examination of the asymmetric reduction of an acetophenone derivative with (+)-B-Chlorodiisopinocampheylborane, it was found that a phenolic MEM ether was slowly cleaved (eq 4). ... 

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