Alcohols, chiral from boranes

Optically active TV-sulfonylamino alcohols derived from D-camphor or norephedrine were found to be efficient chiral ligands for the enantioselective allylboration of iV-silylimines (Equation (170)) 646-648 B-Allyl(diisopinocampheyl)borane allylated iV-diisobutylaluminum imines with 87% ee (Equation (171)).649,650... 

Chiral homoallylic alcohols, The glycol 1 has been used as the chiral matrbt in an enantioselective synthesis of homoallylic alcohols (4) from aldehydes and allyl-boranes (equation I). 

A variety of optically active amines and amino alcohols have been used as chiral auxiliaries for borane reductions. With few exceptions9, early results gave poor to modest asymmetric induction. For example, a variety of amino alcohols derived from a-amino acids gave reduction products of up to 60% ee1U. These reagents presumably used one equivalent of borane per mole of amino alcohol. In 1983 it was shown that the ratio of borane to amino alcohol was important and that two equivalents of borane were required for maximum asymmetric induction. It was postulated that an amino-borane complex of an oxazaborolidinc was involved in the reduction11. 

Yamamoto et al. [16] envisaged that acyloxy-boranes might behave as mixed anhydrides because of the electronegative trivalent boron atom and could serve as effective asymmetric catalysts in selected reactions. In the presence of 20 mole% of chiral acyloxy borane (CAB) complex 7 prepared from 2R,3R)-2-0-(2,6-diisopropoxybenzoyl)tartaric acid and BHs THF, various allyltrimethylsilanes react with achiral aldehydes to afford the corresponding homoallylic alcohols in good yield and high enantio- and diastereoselectivity (Scheme 3). 

One of the more widely used solutions to this challenge is the chiral borohydride analogue invented by Itsuno in Japan and developed by Corey, Bakshi, and Shibata. It is based on a stable boron heterocycie made from an amino alcohol derived from proline (see the box below for the synthesis), and is known as the CBS catalyst after its developers. The active reducing agent is generated when the heterocycie forms a complex with borane. Only catalytic amounts (usually about 10%) of the boron heterocycie are needed because borane is sufficiently reactive to reduce ketones only when complexed with the nitrogen atom. The rest of the borane just waits until a molecule of catalyst becomes free. 

Many other allylborating agents (12-21) utilizing chiral auxiliaries derived from carenes, camphor, tartaric acid, stein, etc. are also known (Figure 2) (2i-33). Recently Villieras described an ester-containing chiral allylborating agent which could be used directly for the synthesis of a-methylene-y-butyrolactones (32). In this review, we have restricted our discussions to the synthesis of lactones via homoallylic alcohols derived from B-allyldiisopinocampheyl-borane, 1. 

The hydrosilylation of ketones is referred to above when a chiral phosphine-platinum (ii) complex is used as catalyst, chiral alcohols are obtained, as their silyl ethers, in optical yields of 5-18%. Chiral alcohols are also obtained in 15-20 % optical yield by condensation of ketones with magnesium alcoholates derived from N-methylephedrine. A study of the chiral reducing system, a-phenylethylamine-borane, has been referred to previously, as has Corey s refinement of prostaglandin reduction. 

Masamune subsequently developed the trans-dimethylborolane 104, which furnishes optically pure alcohols starting from cis- and trans-disubstituted alkenes as well as their trisubstituted counterparts [44]. The inherent structural simplicity of 104 as a reagent for asymmetric hydroboration is, unfortunately, overshadowed by the fact that preparation of the chiral borane 104 is rather labor-intensive. 

The most successful of the Lewis acid catalysts are oxazaborolidines prepared from chiral amino alcohols and boranes. These compounds lead to enantioselective reduction of acetophenone by an external reductant, usually diborane. The chiral environment established in the complex leads to facial selectivity. The most widely known example of these reagents is derived from the amino acid proline. Several other examples of this type of reagent have been developed, and these will be discussed more completely in Section 5.2 of part B. 

Since the discovery of the CBS catalyst system, many chiral //-amino alcohols have been prepared for the synthesis of new oxazoborolidine catalysts. Compounds 95 and 96 have been prepared93 from L-cysteine. Aziridine carbi-nols 97a and 97b have been prepared94 from L-serine and L-threonine, respectively. When applied in the catalytic borane reduction of prochiral ketones, good to excellent enantioselectivity can be attained (Schemes 6-42 and 6-43). 

Borane reduction catalyzed by chiral oxazaborolidines (CBS reduction, CBS = Corey, Bakshi, and Shibata) exhibits excellent enantio- and chemoselectiv-ity for a wide variety of ketonic substrates (Figure 1.27). This reaction was originally developed as a stoichiometric system consisting of diphenylvalinol and borane, ° but was later extended to a useful catalytic method. Because of the high efficiency of this reaction, many chiral oxazaborolidines have been synthesized from p-amino alcohols.Among them the prolinol-derived oxazaboro-lidine is one of the most widely used catalysts. ... 

Reduction of a, -acetylenic ketones with chiral borane NB-Enanthrane prepared by addition of 9-borabicyclo[3.3.1]nonane to the benzyl ether of nopol yielded optically active acetylenic alcohols in 74-84% yields and 91-96% enantiomeric excess [770]. Another way to optically active acetylenic alcohols is reduction with a reagent prepared from lithium aluminum hydride and (2S, 3R)-( -I- )-4-dimethylamino-3-methy 1-1,2-dipheny 1-2-butanol. At —78° mainly R alcohols were obtained in 62-99% yield and 34-90% enantiomeric excesses [893]. 

Highly enantioenriched 4-alken-l-yn-3-ol moieties present in many bioactive acetylenic metabolites from sponges have been efficiently obtained by reduction of the parent 1-trimethylsilyI-4-alken-l-yn-3-one 18 with Alpine-borane or with BH3-SMe2 in the presence of chiral oxazaborolidines, followed by desilylation of the resulting alcohol. This strategy has been applied to the first stereoselective synthesis of petrofuran 19 <99SL429>. 

High stereoselectivities (94-100 %) are attained in the reduction of aromatic ketones by use of a new chiral borane complex with (S)-2-amino-3-methyl-l,l-diphenylbutan-l-ol,(S-68) readily prepared in two steps from (S)-valine, in an experimentally convenient procedure961. (S)-Valine methyl ester hydrochloride was converted with excess of phenylmagnesium bromide into (S-68). The same treatment of (R)-valine gave (R-68). In a typical asymmetric reduction the reagent, prepared from (S-68) and borane, and the ketone (69) in tetrahydrofuran were kept at 30 °C for some hours. The corresponding alcohols were obtained in high optical purity. (S-68) could be recovered to more than 80% without racemization 96). 

Asymmetric reduction of a,f -acetylenic ketones. This borane can be used to reduce 1-deulerio aldehydes to chiral (S)-l-deulerio primary alcohols in 90% optical yields. It also reduces a,/ -acctylcnic ketones to (R)-propargylic alcohols with enantiomeric purity of 73-100%. The ee value is increased by an increase in the size of the group attached to the carbonyl group. The value is also higher in reductions of terminal ynones. Alcohols of the opposite configuration can be obtained with the reagent prepared from (— )-a-pinene. 

Borane and aluminum hydrides modified by chiral diols or amino alcohols are well-known, effective reagents for the stoichiometric enan-tioselective reduction of prochiral ketones and related compounds (34). Reduction of prochiral aromatic ketones with the Itsuno reagent, which is prepared from a chiral, sterically congested /3-amino alcohol and borane, yields the corresponding secondary alcohols in 94-100% ee... 

If the C-terminal component of a t t[CH2-S] pseudodipeptide derives from Gly, such compounds can be prepared by the simpler approach shown in Scheme 6. Borane treatment reduces the amino acid 14 to the amino alcohol 15 which is then further converted into the tosylate 16 with retention of the chirality in the N-terminal component 36 as described previously. Reaction of 16 with the disodium salt 17 of the commercially available sulfe-nylacetic acid yields the pseudodipeptide 18. 

Subsequent transfer of a hydride ion occurs highly stereoselec-tively by way of a six-membered transition state to produce 44. Bi-cydic system 40 is regenerated from 44 with the elimination of compound 45, and 40 reacts with the borane or with 44 to give the corresponding adduct 41 thereby completing the catalytic cycle. Chiral alcohol 46 is released by hydrolysis of 45. 

The oxazolidin-2-ones 53 (R = H=CCH=CH2 or COEt) are obtained in a one-pot reaction of amino alcohol carbamates 52 with sodium hydroxide, followed by allyl bromide or propi-onyl chloride (94TL9533). A modified procedure for the preparation of chiral oxazolidin-2-ones 56 from a-amino acids 54, which avoids the hazardous reduction of the acids with borane and the intermediacy of water-soluble amino alcohols, is treatment of the methyl ester of the amino acid with ethyl chloro-formate to give 55, followed by reduction with sodium borohydride and thermal ring-closure of the resulting carbamate f95SC561). The 2-prop-ynylcarbamates 57 (R = Ts, Ac, Bz, Ph or allyl) cyclize to the methyleneoxazolidinones 58 under the influence of silver cyanate or copper(I) chloride/triethylamine (94BCJ2838). 

Many chiral auxiliaries are derived from 1,2-amino alcohols.7 These include oxazolidinones (l),7-9 oxazolines (2),10 11 bis-oxazolines (3),1213 oxazinones (4),14 and oxazaborolidines (5).15-17 Even the 1,2-amino alcohol itself can be used as a chiral auxiliary.18-22 Other chiral auxiliaries examples include camphorsultams (6),23 piperazinediones (7),24 SAMP [(S)-l-amino-2-methoxy-methylpyrrolidine] (8) and RAMP (ent-8),25 chiral boranes such as isopinocampheylborane (9),26 and tartaric acid esters (10). For examples of terpenes as chiral auxiliaries, see Chapter 5. Some of these auxiliaries have been used as ligands in reagents (e.g., Chapters 17 and 24), such as 3 and 5, whereas others have only been used at laboratory scale (e.g., 6 and 7). It should be noted that some auxiliaries may be used to synthesize starting materials, such as an unnatural amino acid, for a drug synthesis, and these may not have been reported in the primary literature. 

As we saw in Chapter 7, one of the goals of synthetic organic chemistry is to develop methods that produce only a single enantiomer of a desired chiral compound rather than the usual racemic mixture that is the result of most reactions. Recently, a method has been developed that employs one enantiomer of a chiral borane to prepare a single enantiomer of a chiral alcohol from an achiral alkene. The chiral borane that is used is /rans-2,5-dimethylborolane. 

The Focus On box on page 433 described a hydroboration reaction that produces a single enantiomer of a chiral alcohol as the product. The chirality of one enantiomer of the boron hydride reagent is used to control the formation of a single enantiomer of the product. As discussed in that Focus On box, the drawback to this reaction is that it requires one mole of the chiral borane for each mole of chiral alcohol that is produced. The chiral reagent is rather expensive because it must be resolved or prepared from another enantiomerically pure compound. A more desirable process would use the expensive chiral reagent as a catalyst so that a much smaller amount could be employed to produce a larger amount of the chiral product. 

The excellent enantioselectivity and wide scope of the CBS reduction have motivated researchers to make new chiral auxiliaries [3]. Figure 1 depicts examples of in situ prepared and preformed catalyst systems reported since 1997. Most of these amino-alcohol-derived catalysts were used for the reduction of a-halogenated ketones and/or for the double reduction of diketones [16-28]. Sulfonamides [29,30], phosphinamides [31], phosphoramides [32], and amine oxides [33] derived from chiral amino alcohols were also applied. The reduction of aromatic ketones with a chiral 1,2-diamine [34] and an a-hydroxythiol [35] gave good optical yields. Acetophenone was reduced with borane-THF in the presence of a chiral phosphoramidite with an optical yield of 96% [36]. 

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