Catecholborane reductions

Meier, C., and Laux, W.H.G., Asymmetric synthesis of chiral, nonracemic dialkyl a-, P-, and y-hydroxyalkylphosphonates via a catalyzed enantioselective catecholborane reduction. Tetrahedron Asymmetry, 6, 1089, 1995. 

The catecholborane reduction of 2-benzoylpyridine in the presence of 4c gave only a low ee. However, high enantioselectivity (99%) was achieved in the reduction of the hl-allylpyridinium ketone derivative [90]. 

COREY Enalioselaclive borane reduction Enantioselective reduction ol ketones by borane or catecholborane catalyzed by oxazaborolldine 3... 

CONJUGATE REDUCTION OF ,P-UNSATURATED p-TOLUENESULFONYLHYDRAZONES TO ALKENES WITH CATECHOLBORANE 5P-CHOLEST-3-ENE... 

One most important observation for the mechanistic discussion is the oxidative addition/insertion/reductive elimination processes of the iridium complex (31) (Scheme 1-10) [62]. The oxidative addition of catecholborane yields an octahedral iridium-boryl complex (32) which allows the anti-Markovnikov insertion of alkyne into the H-Ir bond giving a l-alkenyliridium(III) intermediate (34). The electron-... 

In 2000, Woodward et al. reported that LiGaH4, in combination with the S/ 0-chelate, 2-hydroxy-2 -mercapto-1,1 -binaphthyl (MTBH2), formed an active catalyst for the asymmetric reduction of prochiral ketones with catecholborane as the hydride source (Scheme 10.65). The enantioface differentiation was on the basis of the steric requirements of the ketone substituents. Aryl w-alkyl ketones were reduced in enantioselectivities of 90-93% ee, whereas alkyl methyl ketones e.g. i-Pr, Cy, t-Bu) gave lower enantioselectivities of 60-72% ee. 

The corresponding A-butyloxazaborolidine is also frequently used as a catalyst. The enantioselectivity and reactivity of these catalysts can be modified by changes in substituent groups to optimize selectivity toward a particular ketone.150 Catecholborane can also be used as the reductant.151... 

Another approach to (R)-(-)-phoracantholide I (245) used a ring enlargement of cyclohexanone (255) which had been alkylated with chiral synthon 256 (Scheme 14) [206]. Thus, compound 257 was prepared in 35% yield on a 7-g scale by alkylation of cyclohexanone with chiral 256. Cyclization with Am-berlyst A-15 provided enol ether 258 that was directly submitted to ruthenium tetroxide oxidation to give oxolactone 259 in a 47% yield. Reduction of the latter with catecholborane via its tosylhydrazone afforded (R)-(-)-phoracan-tholide I (245) in 31% yield. 

First-order kinetics have been found for the reductions of pinacolone by borane-dimethyl sulfide in THF, which proceeds via a monoalkoxyborane complex. In contrast, the kinetics were second order for the reduction with catecholborane and the reactive species was found to be a catecholborane dimer present in small concentrations. 

Reduction of a, -unsaturated ketones to unsaturated hydrocarbon is rather rare, and is almost always accompanied by a shift of the double bond. Such reductions are accomplished in good to high yields by treatment of the p-toluenesulfonylhydrazones of the unsaturated ketones with sodium borohydride [785], borane [786] or catecholborane [559], or by Wolff-Kizhner reduction or its modifications [590]. However, complete reduction to saturated hydrocarbons may also occur during Wolff-Kizhner reduction [597] as well as during Clemmensen reduction [750]. 

Alkynes are reactive toward hydroboration reagents. The most useful procedures involve addition of a disubstituted borane to the alkyne. This avoids the complications which occur with borane that lead to polymeric structures. Catecholborane is a particularly useful reagent for hydroboration of alkynes.168 Protonolysis of the adduct with acetic acid results in reduction of the alkyne to the corresponding Z-alkene. Oxidative workup with hydrogen peroxide gives ketones via enol intermediates. 

This adduct can be prepared, stored, and used as a stoichiometric reagent if so desired.97 Catecholborane can also be used as the reductant.98... 

The CBS-reduction [137] of prochiral ketones is a well-known process which employs a chiral oxazaboroHdine as catalyst and BHs-THF or catecholborane as stoichiometric reductants. It is believed that the active catalytic species is a LLA, resulting from coordination of the oxazaborolidine nitrogen with the boron reagent to render the oxazaborolidine boron atom highly Lewis acidic [87]. Similarly, Corey... 

Bandini and co-workers studied the zinc triflate-bis(oxazohne)-catalyzed reduction of a-alkoxy-ketones with catecholborane. The example in Figure 9.76 shows the reduction of a-methoxyacetophenone 252. l-Phenyl-2-methoxyethanol 254 was isolated in 78% yield and 82% ee. 

An indirect method of accomplishing the reaction is reduction of tosylhydrazones (R2C=N—NHTs) to R2CH2 with NaBH4, BH3, catecholborane, bis(benzyloxy)borane. 

NaBH3CN, or bis(triphenylphosphine)copper(I) tetrahydroborate.531 The reduction of a, (3-unsaturated tosylhydrazones with NaBH3CN, with NaBH -HOAc, or with catecholborane proceeds with migration of the double bond to the position formerly occupied by the carbonyl carbon, even if this removes the double bond from conjugation with an aromatic ring,532 e.g.. 

See catecholborane for a mild and selective alternative to the Wotff-Kishner reduction. 

Reactions using catecholborane proceed smoothly in toluene (Scheme 16) (40). The utility of catalytic hydroboration of ketones has been demonstrated by the efficient enantioselective synthesis of a series of biologically active compounds (41). Scheme 17 shows some compounds prepared by using this method. Enantioselective reduction of trichloro-methyl ketones is a general route to a-amino acids and a-hydroxy esters it also allows ready synthesis of a precursor to the carbonic anhy-drase inhibitor MK-0417 (42). 

An alternative procedure is to convert the carbonyl compound into the toluene-p-sulphonylhydrazone,12 followed by reduction with either sodium borohydride in acetic acid,13 or with catecholborane, followed by decomposition of the intermediate with sodium acetate or tetrabutylammonium acetate.14 The former method is illustrated by the conversion of undecan-6-one into undecane (Expt 5.6), and the latter by the conversion of acetophenone into ethylbenzene (Expt 6.4, Method B). A feature of these methods is that with a, / -unsaturated ketones, migration of the carbon-carbon multiple bond occurs thus the tosylhydrazone of isophorone gives 3,3,5-trimethylcyclohex-l-ene, and the tosylhydrazone of oct-3-yn-2-one gives octa-2,3-diene. 

An alternative milder procedure is the reduction of the corresponding toluene-p-sulphonylhydrazones with catecholborane, followed by decomposition of the intermediate with sodium acetate in the presence of dimethyl sulphoxide, or with tetrabutylammonium acetate.1 These methods, which do not have the disadvantages of the Clemmensen reduction, are illustrated by the preparation of ethylbenzene from acetophenone (Expt 6.4, Methods A and B). Outline mechanisms for these reactions are given below. 

Method B. The toluene-p-sulphonylhydrazone of acetophenone (0.721 g, 2.5 mmol) (1), m.p. 140—141.5 °C, is placed in a flame-dried, nitrogen-filled flask containing 5 ml of chloroform. Catecholborane (0.52 ml, 5.0 mmol) (Section 4.2.7, p. 420) is added and the reduction allowed to proceed for 2 hours at room temperature (2). Methanol (1 ml) is added to destroy the excess of hydride followed by the addition of tetrabutylammonium acetate (0.7 g, 2.5 mmol). The reaction mixture is stirred for 4 hours when g.l.c. analysis indicates a 94 per cent yield of ethylbenzene. The product is isolated by distillation, yield 0.21 g (79%), b.p. 132-136 °C. 

Chiral C2-symmetric boron bis(oxazolines) act as enantioselective catalysts in the reduction of ketones promoted by catecholborane.321 DFT calculations indicate that the stereochemical outcome is determined by such catalysts being able to bind both the ketone and borane reducing agent, activating the latter as a hydride donor, while also enhancing the electrophilicity of the carbonyl. X-ray structures of catalyst-catechol complexes are also reported. 

Reaction of achiral and chiral bis(oxazolines) (BOX) with catecholborane (CATBH) provides boron-BOXate complexes that can be used as catalysts in the enantioselective reduction of ketones. It has been shown that asymmetric transfer of the hydride ion from the boron atom of CATBH to the prochiral carbonyl is the rate-determining step of the catalytic reaction.314... 

Addition of lithium bis(trimethylsilyl)amide to perfhiorinated ketones and solvolysis of the N-Si bond in methanol resulted the formation of stable, isolable N-H imine Z-E isomer mixtures along with a methanol adduct. Enantioselective reduction of these three-component mixtures with oxazaborolidine catalysts and catecholborane provided trifluoromethylated amines in 72-95% yields and 75-98% ee 267... 

These products are biologically significant as some of these phosphonates have been observed to be potent inhibitors of proteolytic enzymes such as rennin and HIV protease. Stereoselective reduction of aminoketophosphonates using catecholborane provides a facile access to these biologically important molecules. 

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