Preparation alpine borane

Fig. 7. Preparation of Alpine-borane (93) and use in the synthesis of homochiral butyrolactones and arylhydroxytetronic acids. Rg and denote small and...

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 ... 

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. 

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).

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... 

Form Supplied in 0.5 M solution in THF. (7 )-Alpine-Borane is prepared from (+)-a-pinene, and (S)-Alpine-Borane from (—)-a-pinene. High purity a-pinene is available commercially. 

Reduction of Aldehydes. Stereospecificially labeled primary alcohols are useful in biochemical and physical organic studies. Such compounds may be prepared by enzymatic reduction of a labeled aldehyde using yeast. However, isolation of the product is often tedious. Alpine-Borane greatly simplifies the process and provides compounds of high enantiomeric purity. It is the most efficient reagent available for reduction of aldehydes. The limiting... 

Alpine-Borane,prepared by hydroborationofa-pinenewith9-borabicyclo[3.3. Ijnonane (9-BBN), reduces aldehydes, a-keto esters and acetylenic ketones with excellent enantioselectivity. The reduction proceeds via a cyclic process similar to the MPV reaction. 

The first total synthesis of the neuritogenic spongean polyacetylene lembehyne A was accomplished by M. Kobayashi and co-workers. The single stereocenter of the molecule was introduced via the Midland reduction of a propargylic ketone using an Alpine-Borane , which was prepared from (+)-a-pinene and 9-BBN. 

Another excellent way to produce enantiomerically pure secondary alcohols is to use chiral organoboranes. After the work pioneered by Brown, many reagents have been developed, such as p-3-pinanyl-9-borabicyclo-[3.3.1]-nonane (Alpine-Borane) (2) and chlorodiisopinocampheylborane (Ipc2BCl) (3) [4]. The latter is now commercially available at scale, and is a useful reagent to reach high chemical and optical yields. A good example of its efficacy has been reported in the preparation of the antipsychotic, BMS 181100, from Bristol-Myers. 

Trialkylborohydrides prepared from optically active alkenes may be used for asymmetric-reduction. For example, reaction of fcrt-butyllithium with Alpine-borane, prepared by hy-droboration of ( + )- or ( —)-a-pinene with 9-borabicyclo[3.3.1]nonane (see Section D.2.3.5.1.), provides Alpine-hydride. 1 his reagent reduces 1-phenylethanone in 17% ee72. A more effective reagent is NB-Enantride, prepared in a similar manner by treatment of the product from hydroboration of the benzyl ether of 2-(2-hydroxyethyl)-6,6-diinethylbicyclo[3.3.1]hept-2-ene (nopol. see Section D.2.3.5.1.) with toV-butyllithium73. 

The 9-(3-pinanyl)-9-borabicyclo 3.3.1]nonane reagent may be prepared from either ( + )- or (—)-x-pinene by hydroboration with 9-BBN. The organoborane derived from (+)- -pinene exhibits a negative rotation and is designated as (—)-(/ )-Alpine-Borane. Normally, cx-pinene is 92% enan-tiomcrically pure. Enriched pinene may be prepared10 or obtained from commercial sources. 

Reduction of aldehydes labeled with deuterium or tritium leads to primary alcohols which are chiral by virtue of the label. Alternatively, the label can be introduced by the use of deuterated Alpine-Borane, which can be prepared by hydroboration with 9-borabicyclo[3.3.1]nonane-... 

Scheme 7.5. Alpine-borane method of asymmetric reduction, (a) Preparation of Alpine-Borane . (b) Reduction of deuterio benzaldehyde [52], (c) Reduction of propargyl ketones...

Synthetic samples of (4 S)- and (4 i )-[4 - Hi]- and [4 - Hi]pyridoxamine 20a were prepared by the route outlined in Scheme 11, the key step being reduction of the labeled pyridoxal derivatives 32 with alpine boranes (32). 

In Ramalingam and Woodard s synthesis (117) the protected aspartate semialdehyde 113 was synthesized from (2S)-aspartic acid and then converted to the labeled alcohols 115 using (R)- and (S)-alpine boranes (Scheme 33). Hydrolysis then led directly to (2S,4R)- and (2S,4S)-[4- H,]homoserine lactones 112. Since the enzyme aspartase may be used to prepare samples or (2S, 3R)-[3- H J- and (2S, 3S)-[2,3- H2]aspartate (see Section IX), the synthesis, or a modification using more direct reduction methods, could be... 

Therefore, this avoids the necessity of prior preparation [6] of 1-deuterated aldehydes. The absolute configuration of the major products are consistently K)- when deuterated Alpine-Borane (from (+)-a-pinene) is used for the reduction. The product of (S)-configuration is readily obtained by using deuterated B-3-pinanyl-9-BBN prepared from (-)-a-pinene and 9-BBN-9-D. On the other hand, reduction of deuterated aldehyde with Alpine-Borane from (-h)-a-pinene affords (S)-alcohols and (f )-alcohols are obtained when (-)-a-pinene is used (Chart 26.3). 

The following model (Fig. 26.1) explains the delivery of deuterium for chiral reduction of aldehydes from Alpine-Borane prepared from (+)-a-pinene. 

The stereochemical outcome of the reduction is predicted by the following model [14] for Alpine-Borane prepared from (-i-)-a-pinene. The hydride transfer occurs from the boat-like transition state in which the acetylene occupies the axial position (Eig. 26.3). 

An efficient stereoselective reduction of 22-keto-23-acetylenic steroid to anti-Cram product 22-(R)-hydroxy-23-acetylenic steroid and Cram product 22-(S)- hydroxy-23-acetylenic steroid has been achieved using (R)-Alpine-Borane [(-i-)-a-pinene, 92% ee] (125 1, R-.S) and L-selectride (lithium tri-sec-butylboro-hydride) (1 11, R S), respectively [19] (Chart 26.7). (S)-Alpine-Borane (2 M in THE) prepared from (-)-a-pinene (92% ee) provides unexpectedly low 1 2.7, R S ratio due to the influence of the a-chiral center at C-20 of the steroid, and also the reduction is much slower than with (R)-Alpine-Borane. 

Brown and coworkers [1] have found that NB-Enantrane is effective only for the reduction of a,(3-acetylenic ketones. The reduction of other ketones is too slow to be of any practical use. The retarded rate is attributed to the steric bulk at the 2 position since no internal coordination has been detected by "B NMR (6 86 ppm) [2]. On the other hand, Alpine-Borane has proven to be versatile reagent for the asymmetric reduction of variety of ketones. Consequently, two reagents B-(iso-2-ethylapopinocampheyl)-9-borabicyclo[3.3.1]nonane (Eapine-Borane) and B-(iso-2- -propylapopinocampheyl)-9-BBN (Prapine-Borane) having increasing steric requirement at the 2 position, are prepared by the hydroboration [3] of 2-ethyl- and 2-n-propylapopinene. 

The reagent Eapine-Borane, prepared (Eq. 26.15) from (-)-2-ethylapopinene by hydroboration with 9-BBN have been studied for its reaction with representative ketones and is found to react at faster rate than NB-Enantrane, but at slightly slower rate than Alpine-Borane (Table 26.15) [1]. 

Prapine-Borane is prepared neat from (-)-2- -propylapopinene by hydrobo-ration with solid 9-BBN, using the same procedure as used for the preparation of Alpine-Borane and Eapine-Borane. (-)-2- -Propylapopinene is prepared in 84% yield from nopyltosylate by treatment with dimethylcuparate, prepared in situ [5] from methyllithium and cuprous iodide (Scheme 26.4). 

It is found that incorporation of an oxygen into the chiral ligand provides a fixed coordination site for lithium and hence to a more rigid and thus more ste-rically demanding transition state. The NB-Enantride reduces acetophenone to (S)-phenylethanol (Eq. 26.22), whereas the Alpine-Borane prepared from (-)-a-pinene gives the (7 )-enantiomer [4]. 

In summary, this chapter shows that organoboron-based asymmetric reducing agents, such as K Glucoride (1), K Xylide (2), Alpine-borane (3), Dip-Chloride (4) and oxazaborolidine-catalyzed boranes are highly effective for the reduction of a variety of a-functionalized ketones. We have established a convenient and simple procedure for the preparation of terminal 1,2-diols, a-hydroxy acetals and epoxides with very high optical purity via oxazaborolidine-catalyzed borane reduction using /V-phenylamine-borane complexes as the hydride source. 

Alpine-Borane (Midland) Alpine-Borane is a trademark of Aldrich Chemical Company for B-3-pinanyl-9-borabicyclo[3.3.1]nonane. It is prepared by hydroboration of a-pinene with 9-borabicyclo[3.3.1]nonane (9-BBN). Synthesis of (1 )-Alpine-Borane is prepared from (17 )-(+)-a-pinene, and since (+)- and (-)-a-pinenes are commercially available, both enantiomers of the reagent can easily be prepared. The reagent is only suitable for very reactive substrates, such as labeled aldehydes and acetylenic ketones (Scheme 2.136) [64],... 

Both catalytic versions compare favorably with the stoichiometric methodology using (+)- or (—)-B-3a-pinanyl-9-BBN ((+)- or ( )-Alpine Borane, 59) in giving an equivalent stereochemical outcome of 80-100% e.e. . Employment of 1 -deutero or 1 -tritio aldehydes as substrates is also highly recommended, in order to avoid the inconvenient preparation of labeled reducing agent. The synthesis of (5)-[2- H, H]acetic acid (60) and (/ )-[l- H]-hexadecyloxypropane-1,2-diol (61) may serve as illustrative examples. 

---