Asymmetric reduction BINAL

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. 

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 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. 

The utility of the BINAL-H asymmetric reduction in other PG syntheses is shown in Scheme 16 (35, 39). This asymmetric reduction is a general method for generating the 15S configuration and is highly practical, because the binaphthol ancillary is easily recovered in reusable form from the reaction mixture. In fact, this reduction is undertaken on a multikilogram scale in the Corey synthesis (Ono Pharmaceutical Co.). The observed high diastereoselectivity leading to the desired 155... 

SCHEME 19. General sense and examples of BINAL-H asymmetric reduction. 

In 1979, Noyori and co-workers invented a new type of chiral aluminum hydride reagent (1), which is prepared in situ from LiAlEE, (S)-l, E-bi-2-naphthol (BINOL), and ethanol. The reagent, called binaphthol-modified lithium aluminum hydride (BINAL-H), affects asymmetric reduction of a variety of phenyl alkyl ketones to produce the alcohols 2 with very high to perfect levels of enantioselectivity when the alkyl groups are methyl or primary1 (Scheme 4.3a). 

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). 

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. ... 

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. 

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... 

The most important feature of the BINAL-H asymmetric reduction is the empirical rule for the orientation observed with simple prochiral carbonyl substrates of type (43) (Un = phenyl, alkenyl, alkynyl R =... 

Asymmetric reduction of prochiral diphenylphosphinylimines (111) by (S)-BINAL-H (28), LAH-Dar-von alcohol complex (48) or K-glucoride (64) affords the (S)-amines (112 Scheme 20). The protecting group of (112) is readily cleaved under acidic conditions to give the free amine. When the alkyl group is methyl or ethyl, (S)-BINAL-H shows high enantioselectivity. - ... 

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.

Figure 7.1. Postulated transition structures for the asymmetric reduction of unsaturated ketones by BINAL-H [12]. Structures (a) and (b) differ in the orientation of Rjat and Run, the saturated and unsaturated ketone ligands, respectively, (a) UI topicity P reagent attacking Re face of ketone, (b) Lk topicity P reagent attacking Si face of ketone, (c) Alternate chair that is destabilized by the gauche pentane conformation accented by the bold lines (c/. Figure 5.5). Transition structures containing this conformation were considered by Noyori to be unimportant [12].

Asymmetric reduction of ketones. A reagent 2, prepared by reaction of LiAlH4 with 1 and C2H5OH (1 equiv. each) in THF at 20°, effects asymmetric reduction of dialkyl ketones or alkyl aryl ketones in 53-93% yield and 60-97% ee. The enantioselectivity is generally greater than that obtained with Noyori s reagent BINAL-H (9,169-170), particularly in reduction of dialkyl ketones in which the alkyl groups have similar steric effects. 

Similarly, asymmetric reduction of alkylaromatic ketones gives high optical yields (Table 26.26) [7], It is noteworthy that the optical yields obtained by K-glucoride in the reduction of hindered ketones such as pivalophenone is 97-100% ee and 87% ee for isobutyrophenone are considerably higher than the values (44 and 71% ee, respectively) obtained with highly promising Binal-H reagent [8] (Eq. 26.27). 

Various catalytic or stoichiometric asymmetric syntheses and resolutions offer excellent approaches to the chiral co-side chain. Among these methods, kinetic resolution by Sharpless epoxidation,14 amino alcohol-catalyzed organozinc alkylation of a vinylic aldehyde,15 lithium acetylide addition to an alkanal,16 reduction of the corresponding prochiral ketones,17 and BINAL-H reduction18 are all worth mentioning. 

SCHEME 15. Asymmetric synthesis of prostaglanding blocks by BINAL-H reduction. 

The BINAL-H reagents exhibit exceptionally high enantioface-dif-ferentiating ability in the reduction of prochiral ketones that have unsaturated substituents such as aromatic rings, olefinic and acetylenic groups, etc. The general sense of asymmetric induction of simple car-... 

The preparation of enantioenriched Q -(alkoxy)allylstannanes has been advanced by the asymmetric Noy-ori reduction of the stannyl ketone 264 with 2,2 -dihydroxy-l,T-binapthyl lithium aluminum hydride (BINAL-H) reagents affording the non-racemic (5 )-265 with > 95% ee, upon O-alkylation with common protecting groups (Scheme 5.2.57, top). °... 

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