Reduction using BINAL

Table 7.1. Asymmetric reductions using BINAL-H. The reactions were conducted by initial reaction at -100° for 3 hours, followed by several hours at -78° C. All examples favor ul relative topicity (see Figure 7.1a). Thus, the M reagent adds to the Si face to give the R product, and vice versa for the P reagent.

A number of structurally diverse ketones have been reduced using BINAL-H. Some of the results are summarized in Table 1. Aryl alkyl ketones, alkynic ketones, and a, -unsaturated ketones are reduced to alcohols with good to excellent % ee, while aliphatic ketones give products with lower optical purities. The asymmetric reduction of a number of acylstannanes with (7) gives synthetically valuable a-alkoxystannanes with high optical purities after protection of the initially formed unstable alcohols as their MOM or BOM ethers. ... 

Scheme 7.2. Yields and enantioselectivities of reduction of meso anhydrides using BINAL-H [17],...

Optically active 1-alkoxyallylstannanes are more readily available by asymmetric reduction of acylstannanes using either ( + )-(/J)-BINAL-Il105 106 or LiAlH4-Darvon alcohol [(2S,3/ )-4-dimethylamino-3-mcthy]-1,2-diphenyl-2-butanol] 06 followed by O-alkylation. The stereoselectivity of the BINAL-H reductions differs from that usually observed, and has been attributed to a tin-oxygen hypervalent interaction107, l08. 

Coleman established the hydroxypropyl stereochemistry via addition of a homochiral a-alkoxyalkyl organometallic species. This reagent was prepared in high enantiomeric excess using a Noroyi BINAL-H reduction of organostannane 33, which was transmetallated with ra-BuLi to achieve the desired organolithium reagent 35 (Scheme 7.5). Both enantiomers of 35 could be obtained via this route. 

Another method for ketone reduction, BINAL-H asymmetric reduction, can also be used in co-side chain synthesis. An example of applying BINAL-H asymmetric reduction in PG synthesis is illustrated in Scheme 7-27. This has been a general method for generating the alcohol with (15. -configuration. The binaphthol chiral auxiliary can easily be recovered and reused. As shown in Scheme 7-27, when the chiral halo enone 91 is reduced by (S -BINAL-H at — 100°C, product (15S)-92 can be obtained with high enantioselectivity. 

The reduction of dialkylketones and alkylaryl ketones is also conveniently accomplished using chiral oxazaborolidines, a methodology which emerged from relative obscurity in the late 1980s. The type of borane complex (based on (,V)-diphenyl prolinol)[39] responsible for the reductions is depicted below (10). Reduction of acetophenone with this complex gives (/ )-1 -phenylethanol in 90-95% yield (95-99% ee) [40]. Whilst previously used modified hydrides such as BiNAL-H (11), which were used in stoichiometric quantities, are generally unsatisfactory for the reduction of dialkylketones, oxazaborolidines... 

The most general way to obtain chiral a-stannylated ethers today consists of the asymmetric reduction of acylstannanes34,35,36 using the 2,2 -dihydroxy-l,T-binaphthyl-modified lithium aluminum hydride (BINAL-H) reagent37 and etherification of the crude alcohol with chloro-methoxymethane. 

In this context, a chiral hydride reagent, BINAL-H, prepared by modification of lithium aluminum hydride with equimolar amounts of optically pure binaphthol and a simple alcohol, is extremely useful (9b, 18a, 35) Scheme 15 shows the utility of the three-component coupling synthesis. The < > side-chain unit and the hydroxycyclopentenone can be prepared with very high enantioselectivity by reduction of the corresponding enone precursors (35-38). 

Enantioselective reduction of ketones. Marshall et al.1 report that more consistent results obtain when BINAL-H is prepared by refluxing a mixture of the binaphthol, LiAlH4, and ethanol in THF for a short time before use. They also note that the expensive binaphthol can be recovered and reused. 

The BINAL-H enantioselective reduction of o.,(j-conjugatcd ketones was used in the total synthesis of (—)-lepadiformine (20), which exhibits moderate cytotoxic activities against various tumor cell lines8 (Scheme 4.3g). A solution of 21 in toluene... 

OXAZOLIDINECARBOXYLATE has previously been described in Volume 70 of Organic Sytheses. An alternative procedure for the preparation of this compound is presented in this volume along with its use in a dia-stereoselective addition reaction with 2-TRIMETHYLSILYLTH1AZOLE to provide a compound bearing a 2-amino-1,3-diol substructure that appears in a variety of natural products. The conversion of abundantly available isosorbide into OSO ISOPROPYLIDENE-l ti-DIANHYDRO-d-GLUCITOL provides a potentially useful carbohydrate-deri ved material for the use in complex tetrahydrofuran synthesis. Finally, asymmetric reduction of an a,j9-unsaturated acylstannane with (R)-BINAL provides access to (S,E)-l-(METHOXYMETHOXY)-l-TRIBUTYLSTANNYL-2-BUTENE, an a-alkoxy allylstannane that has been used in enantioselective vicinal diol synthesis amongst other transformations. 

Reduction of Prochiral Ketones. BINOL has been used as the chiral ligand of the reagent BINAL-H (see Lithium Aluminum Hydride-2,2 -Dihydroxy-1,1 -binaphthyl, Vol. B) for asymmetric reduction. The reagent reduces prochiral unsaturated ketones to the corresponding secondary alcohols in up to 90% yield and >90% ee (eq 7) (f )-BINAL-H leads to the (i )-alcohols while (S)-BINAL-H gives the (S)-alcohols. 

The reagent (7 )- or (S)-BINAL-H (7), developed by Noyori, is undoubtedly the most useful LAH complex reported so far for the asymmetric reduction of a variety of carbonyl compounds." The reagent is prepared from (R)- or (S)-2,2 -dihydroxy-1,T-binaphthyl (3) (BINAL). Both enantiomers of BINAL are commercially available, although they are somewhat expensive. The chiral ligand, however, can be recovered after the reduction and reused. Equimolar quantities of BINAL and LAH are initially mixed together to form a LAH complex that has a C2 axis of sym-... 

The asymmetric reduction of lactone (9) to give predominantly one atropoisomer can be achieved using 10 equiv of a complex prepared from LAH and BINAL (1 1) at —40°C. This reduction gives an 88 12ratio of (10a) (10b) in good yield (80%). Reduction of the same substrate with 8 equiv of a complex of LAH with (S)-(+)-2-(anilinomethyl)pyrrolidine in ether at —40°C leads to opposite stereochemical results (38 62 ratio of 10a 10b). 

BINAL-H has also been used for the asymmetric reduction of methylaryl- and methylalkylphosphinylimines to the corresponding phosphinylamines in high % ee (Table 2). Similar to the reduction of ketones, reduction of the imines with (S)-(7) produces the (S)-amine and reduction with (R)-(7) gives the (R)-amine. 

A sequence was later developed for the synthesis of enantioenriched a-oxygenated allylic stannanes that did not require resolution (Eq. 33) [53]. This sequence, like the former, starts with the addition of BusSnLi to an enal. The resulting lithio alkoxide is oxidized in situ to the corresponding acylstannane. Reduction of the acylstannane with (M)-BINAL-H affords the (5)-a-hydroxy allylic stannane in > 95% ee. The use of (F)-BINAL-H leads to the (R) enantiomer with comparable ee. These hydroxy... 

Achiral ruthenium fragments can also be used with a chiral reductant. The reduction of a [CpRu(DPPE)(thionolactone)] complex with BINAL-H and decomplexa-tion as above gave the thioether in 84 % ee [53],... 

In 1951 Bothner-By first attempted asymmetric reductions based on the conversion of lithium aluminum hydride (LAH) into a chiral alkoxy derivative by reaction with (+)-camphor. Since this pioneering work, the use of chirally modified LAH reagents has been the focus of much attention. In 1979, the first virtually complete enantiofacial recognition of prochiral carbonyl compounds was accomplished by using LAH modified with optically pure 2,2 -dihydroxy-1,1 -binaphthyl and a simple alcohol (BINAL-H). Asymmetric reduction with chiral 2,5-dimethylborolane also gave alcohols in high optical yields." Recently, excellent results have been obtained using a chirally modified sodium borohydride... 

Y-Silyloxy allylstannanes can be prepared in a direct manner from a-hydroxy allylstannanes [56]. The substrates are prepared by standard enantioselective reduction conditions such as BINAL-H from the corresponding stannyl ketones [53a,bj. The isomerization process of a-hydroxy allylstannane 148 to y-silyloxy allylstannane 151 proceeded when TBSOTf was used as a silylating reagent When TBSCl was used instead no isomerization took place, but a-silyloxy allylstannane 149 was obtained instead. 

A wide variety of chiral modifications of the commonly employed reducing agent lithium aluminum hydride have been examined [23, 111, 112). Noyori described one of the most effective reagents namely BINAL-H (176), produced upon treating LiAlH4 with BINOL (Equation 17) [122, 123]. BINAL-H has been shown to be particularly useful in the enantioselective reduction of aromatic and unsaturated ketones [111]. For example, reduction of 175 with (S)-BINAL-H furnishes 177 in 92% yield and with >99% ee [122]. 

---