Ketones, from boranes

Formation of Alkynes, Alkenes, and Ketones from Boranes and Acetylides... 

New chiral oxazaborolidines that have been prepared from both enantiomers of optically active inexpensive a-pinene have also given quite good results in the asymmetric borane reduction of prochiral ketones.92 Borane and aromatic ketone coordinate to this structurally rigid oxazaborolidine (+)- or (—)-94, forming a six-membered cyclic chair-like transition state (Scheme 6-41). Following the mechanism shown in Scheme 6-37, intramolecular hydride transfer occurs to yield the product with high enantioselectivity. With aliphatic ketones, poor ee is normally obtained (see Table 6-9). 

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. 

The use of chiral oxazaborolidines as catalysts for the enantioselective addition of alkynylboranes to aldehydes took place in a manner analogous to the asymmetric reduction of ketones with boranes mediated by proline-derived oxazaborolidines (Equation (127)).587 Addition of alkynylboranes to A-aziridinylimines provided a convenient method to prepare allenes from carbonyl compounds (Equation (128)).5... 

Enantioselective Ketone Reduction. After the pioneering work of Itsuno et al., Corey s group isolated the 1,3,2-oxazaborolidine derived from chiral a,a-diphenyl-2-pyrrolidinemethanol (2) and applied it (and also other related B-alkyl compounds) to the stereoselective reduction of ketones with borane-tetrahydrofuran, borane-dimethyl sulfide (BMS) or catecholborane.It was named the CBS method (after Corey, Bakshi, and Shibata). Since then, the CBS method has become a standard and has been extensively used, specially for aromatic and a,p-unsaturated ketones, not only in academic laboratories but also in industrial processes. ... 

The reduction of ketones by borane catalyzed by chiral oxazaborolidines such as (136), derived from the enantiomeric amino alcohols, has been applied to the synthesis of several drug candidates (127). This system is known as the CBS (Corey, Bakshi, Shibata) reduction (153), and Corey himself has applied it to the synthesis of pharmaceutical compounds (154). A further example is provided by the synthesis of MK-499 (137), a... 

Oxazaborolidenes. Corey has reported the use of a novel oxazaborolidene complex 41 prepared from borane and A-tosyl (5)-tryptophan. This complex functions in a catalytic fashion in enantioselective, Mukaiyama aldol addition reactions (Scheme 8-3) [17]. The addition of ketone-derived enol silanes 42-43 gives adducts in 56-100% yields and up to 93% ee. The use of 1-trimethylsilyloxycyclo-pentene 43 in the addition reactions to benzaldehyde affords adducts 46 as a 94 6 mixture of diastereomers favoring the syn diastereomer in 92% ee. Addition reactions with dienol silanes 44 furnishes products 47 in up to 82% ee. Corey also demonstrated the use of these adducts as important building blocks for the synthesis of corresponding dihydropyrones treatment of 47 with trifluoroacetic acid affords the cyclic product in good yields. 

This high activity of the catalyst 19 can be explained by its amphoteric properties since it is able to activate simultaneously both ketone and borane. This assumption led to a mechanistic proposal rationalizing the hydride transfer from the borane on the phosphorus atom to a ketone coordinated to the other boron atom acting as a Lewis acid. 

Reduction. Secondary alcohols with moderate ee values are obtained from the reduction of ketones with borane in the presence of such a complex. 

One of the outstanding discoveries of recent years is the enantioselective reduction of prochiral ketones with borane in the presence of catalytic amounts of oxazaborolidenes obtained from L-proline (reaction 9.10), and termed... 

Reaction of boranes with diazo compounds Synthesis of ketones from ethylene derivatives... 

There are also a variety of asymmetric catalytic reactions which may produce optically active alcohols. Metalo-organic compounds have been reported to play an essential role in some of them. One of these reactions is enantioselective reduction of pro-chiral ketones with borane in which BHj-SMe adduct are used as reductant. It also needs a chiral ligand along with aluminum isopropoxide to prepare enantioenrich compounds (reaction 7.7). Fu and Uang used (R)-binaphthol as chiral ligand and without use of AKOTrlj, reached 50% yield with no enantioselectivity in production of phenyl ethanol 63, from acetophenone 62, by BH -SMe even after 24 hours [54]. But in the presence of both, at 40°C, 96% yield with 74%... 

Dilithium tetrachlorocuprate is recommended as an additive for cross coupling of Grignard compounds with tosylates even allylic and benzylic acetates give good yields . a-Methylene-ketones, -carboxylic acids and -lactones have been prepared via sulfides and sulfoxides. A convenient and general synthesis of acetylene derivatives from boranes via the reaction of iodine with lithium 1-alkynyltriorganoborates has been published ar-Nitrostyrenes can be easily obtained by a Wittig synthesis with formaldehyde in an aqueous medium . A new synthesis of unsym. ketones by reaction of dialkyldiloroboranes with lithium aldimines has recently been published . Metallo aldimines have also served for the synthesis of a variety of other compound classes such as a-hydroxyketones, a-keto acids, nitriles, and for the asym. synthesis of a-amino acids . Polycondensations of malononitriles with benzylic chlorides have been carried out quantitatively under mild conditions in dimethyl sulfoxide with triethylamine as acid acceptor . Carbonyl compounds can react with dibromoacetonitrile to yield a-bromo esters with additional carbon atom . ... 

Hydroboration of Ketones with Boranes from ot-Pinenes and the Non-linear Effect in Asymmetric Reactions... 

Hydroboration of Ketones with Boranes from a-Pinenes... 

Highly enantioselective reduction of heterocyclic aromatic ketones with borane and the spiroborate ester derived from (S)-diphenyl prolinol... 

Asymmetric reduction of prochiral ketones is one of most efficient method of the introduction of chirality in the synthesis of non-racemic biologically active compounds. Derived from chiral (S)-diphenyl prolinole the amino borate ester 1 has been prepared, fully characterized and used as highly effective catalyst for asymmetric reduction of ketons with borane. The optically pure alcohols 3 have been prepared using only 1 mol % of catalyst 1 in enantioselectivity up to 97%. 

Alkylation.—Position-specific alkylation of ketones can be achieved by a number of new methods. Vinyloxyboranes, formed by reaction of trialkyl-boranes with diazoketones or by radical addition to methyl vinyl ketone, react with alkyl-lithium reagents to give the corresponding lithium enolates, which undergo facile, site-specific alkylation this allows the formation of aa-disubstituted ketones from diazoketones and a/3-disubstituted ketones from methyl vinyl ketone (Scheme 80). 

CBS (Corey, Bakshi, and Shtbata) Catalyst Itsuno [67] paved the way for the discovery of oxazaborolidines as chiral catalysts for the borane-mediated enantioselective reduction of a wide variety of achiral ketones, the so-called CBS reduction. Scheme 2.139 summarizes some of these results and the proposed transition state [68], These data show that the CBS reduction process results in exceUent enanti-oselectivities and leads to a product whose absolute configuration can be predicted from the relative effective steric bulk of the two carbonyl appendages. It is noteworthy that the oxazaborolidine catalyst behaves like an enzyme in the sense that it binds with both ketone and borane and brings... 

Reactions via frans- ,y -ethylene-a-haIogenoborans Ketones from acetylene halides and boranes... 

Pyridyl)hydrazine (Aldrich), 4-acetylpyridine (Acros), N,N,N -trimethylethylenediamine (Aldrich), methylrhenium trioxide (Aldrich), InQj (Aldrich), Cu(N0j)2-3H20 (Merck), Ni(N03)2-6Il20 (Merck), Yb(OTf)3(Fluka), Sc(OTf)3 (Fluka), 2-(aminomethyl)pyridine (Acros), benzylideneacetone (Aldrich), and chalcone (Aldrich) were of the highest purity available. Borane dimethyl sulfide (2M solution in THE) was obtained from Aldrich. Methyl vinyl ketone was distilled prior to use. Cyclopentadiene was prepared from its dimer immediately before use. (R)-l-acetyl-5-isopropoxy-3-pyrrolin-2-one (4.15) has been kindly provided by Prof H. Hiemstra (University of Amsterdam). 

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