Alpine Borane Reduction

Enantioselective reduction is not possible for aldehydes, since the products are primary alcohols in which the reduced carbon is not chiral, but deuterated aldehydes RCDO give a chiral product, and these have been reduced enantioselectively with B-(3-pinanyl)-9-borabicyclo[3.3.1]nonane (Alpine-Borane) with almost complete optical purity. ... 

The synthesis of chiral liquid-crystalline allenes was reported by Tschierske and co-workers (Scheme 4.10) [14]. An asymmetric reduction of 41 with Alpine borane was a key step to an enantioenriched allene 44. After removal of the silyl group, the allenic alcohol was etherified by the Mitsunobu method to give 45, the first liquid-crystalline allene derivatives. 

Asymmetric reduction of ketones using Alpine-borane . Alpine-borane = B-isopinocampheyl-9-borabicyclo[3.3.1]nonane. 

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>. 

The field of organoboron chemistry pioneered by Brown [40] also provides a wealth of excellent transformations. Consider the asymmetric reduction of carbonyl compounds by Alpine-Borane [41]. Alpine-Borane is prepared by the following sequence ... 

The enantioselective reduction of 3-butyn-2-one (7) is achieved in 82 % ee by use of the Eapine-Borane 22.9 Application of the commercial available Alpine Borane leads to a lower enantio-selectivity (77 % ee). The mechanism of this reduction is explained in Chapter 13. 

Borane ). This reagent is commercially available or prepared by hydroboration of (-)-a-pinene (16) with 9-BBN (17).10 The stereoselectivity of carbonyl group reduction with (S)-Alpine Borane is explained via six-membered transition state 18. 

The above described total synthesis features the first enantiodivergent approach to (+)- and (—)-scopadulcic acid A. The central transformations are the stereoselective carbonyl group reduction with (S)-Alpine Borane , the use of enolization stereoselection to dictate which enantiomer is produced, and the palladium-catalyzed bis-Heck cyclization which occurs with complete stereo- and regiocontrol to establish the scopadulan scaffold. 

Figure 3.27 shows reaction equations and the energy relationships of the hydroboration of enantiomerically pure a-pinene with 9-BBN. The reagent approaches only the side of the C=C double bond that lies opposite the isopropylidene bridge. The addition is thus completely diastereoselective. Moreover, the trialkylborane obtained is a pure enantiomer, since the starting material is a pure enantiomer. It is used as Alpine-Borane for the enantioselec-tive reduction of carbonyl compounds (Section 10.4). 

The stereoselectivities of the carbonyl group reductions with Alpine-Borane (Figure 10.24) or with Brown s chloroborane (Figure 10.25) are explained as shown in the for-... 

Fig. 10.24. Asymmetric carbonyl group reduction with Alpine-Borane (preparation Figure 3.27 for the "parachute-like" notation of the 9-BBN part of this reagent see Figure 3.21). The hydrogen atom that is in the cis-position to the boron atom (which applies to both ft- and /T-H) and that after removal of the reducing agent leaves behind a tri- instead of a disubstituted C=C double bond (which applies to ft-, but not / -H) is transferred as a hydride equivalent. In regard to the reduction product depicted in the top row, the designation S of the configuration relates to the aryl-substituted and R to the Rtert-substituted propargylic alcohol.

Fig. 8.19. Asymmetric carbonyl group reduction with Alpine-Borane (preparation Figure 3.21).

Reductions with diisopinocampheylchloroborane [(IPC)2BC1] often afford higher ee values than reductions with Alpine-Borane because (IPC)2BC1 is the stronger Lewis... 

There is a second effect. In the transition state in which the stronger Lewis acid complexes the carbonyl oxygen, the carbonyl group is a better electrophile. Therefore, it becomes a better hydride acceptor for Brown s chloroborane than in the hydride transfer from Alpine-Borane. Reductions with Alpine-Borane can actually be so slow that decomposition of this reagent into a-pincnc and 9-BBN takes place as a competing side reaction. The presence of this 9-BBN is problematic because it reduces the carbonyl compound competitively and of course without enantiocontrol. 

Midland and others reported that B-isopinocampheyl-9-borabicyclo[3.3.l]no-nane [Alpine-Borane (7 )-79] is an effective reagent for the highly asymmetric reduction of alkynyl ketones to afford the propargylic alcohol 8030 (Scheme 4.3z). The reagent (R)-19 is prepared from (+)-a-pinene and 9-borabicyclo[3.3.1]no-nane (9-BBN) and often represented as 19banana. The levels of asymmetric... 

Pinanyl-9-BBN (Alpine borane 4) is a chiral borane that is readily oxidized by aldehydes. Aliphatic deuterioaldehydes undergo chiral reduction to give alcohols widi 84-98% The chiral alkene is regenerated in the process, only the hydrogen at the 2-position having been utilized, and can be reused. Equation (52) serves as an illustration of the stereochemistry of the process. 

The stereoselectivity of carbonyl group reduction with (5)-Alpine Borane is explained via six-membered transition state 18. 

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