Midland Alpine-Borane

MIDLAND ALPINE-BORANE REDUCTION (MIDLAND REDUCTION)... 

Midland Alpine borane reduction Enantioselective reduction of ketones using Alpine borane. 288... 

Related reactions Luche reduction, Midland alpine borane reduction, Noyori asymmetric reduction ... 

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],... 

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... 

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. 

Midland, M. M., Lee, P. E. Efficient asymmetric reduction of acyl cyanides with B-3-pinanyl 9-BBN (Alpine-borane). J. Org. Chem. 1985, 50, 3237-3239. 

Midland, M. M McLoughlin, J. I., Gabriel, J. Asymmetric reductions of prochiral ketones with B-3-pinanyl-9-borabicyclo[3.3.1]nonane (Alpine-Borane) at elevated pressures. J. Org. Chem. 1989, 54,159-165. 

An early success4 was Midland s Alpine-Borane , derived from 9-BBN 28 and a-pinene 22. Hydroboration takes place from the less hindered side of the double bond, away from the gem dimethyl groups, to give alpine borane 29. The reagent works well for acetylenic alcohols and the transition state 30 puts the acetylene in the outside position. 

The Midland reduction is the enantioselective reduction of a ketone (It to an optically active alcohol (2) using the commercially available reagent alpine borane (3). ... 

Alpine borane (the Midland reagent, 3) has found broad use in the synthesis of complex natural products. As early as 1980, only one year after Midland s seminal publication, Johnson and co-workers used 3 for the reduction of ketone 18 to afford alcohol 19 in 75% yield and 97% ee.12 This material was used to complete the synthesis of 20, a cyclization precursor in Johnson s total synthesis of hydrocortisone acetate. 

In a totally different approach, Noyori et al. have used binaphthol-modifled aluminum hydride reagent for enatioselective reduction of alkynyl ketones. Suitably modified boranes can be used for stereoselective reduction of ketones. Along these same lines. Midland" has developed Alpine borane (1, Scheme 21.5), which is excellent for several acetylenic ketones but has been found inefficient for hindered ot,p-acetylenic ketones. To overcome this problem, Brown et al." have introduced P-chlorodiisopinocamphenyl borane 2(-)-DIP-Cl (2, (Scheme 21.5), which reacts well with hindered ketones to provide the corresponding propargyl alcohols in 96 to 99% e.e. 

The systematic studies conducted by Midland and coworkers [8] have shown that among the various B-alkyl-9-BBN obtained from (+)-a-pinene, (-)-(3-pi-nene, (-)- camphene, and (+) 3-carene (Chart 26.2), B-3-pinanyl-9-BBN (Alpine-Borane) shows remarkable enantioselectivity as illustrated in Table 26.1 [8]. 

The, B-3-pinanyl-9-borabicyclo[3.3.1]nonane or Midland s reagent or Alpine-Borane is commercially available [9]. 

Midland and coworkers [Ic] have reported that reduction of alkynyl ketones affords excellent chemical and optical yields that approached 100% in many cases. In general, under Midland s reaction condition, for example, 4-phenyl-3-butyn-2-one takes 48 h for complete reduction at 25 °C with 100% excess of Alpine-Borane. On the other hand Brown has reported [3] the reduction of ketones in 8-12 h, using a 40% excess of the neat reagent (Scheme 26.2 Table 26.12), and products show a substantially higher optical rotation as compared to reported by Midland [Ic]. 

Midland MM, Greer S, Tramontano A, Zderic SA (1979) J Am Chem Soc 101 2352 B-3-Pinanyl-9-borabicyclo[3.3.1]nonane is commercially available from Aldrich Chemical Co. under the trademark Alpine-Borane. 

An earlier breakthrough in chiral reductions was made by Midland and co-workers who demonstrated that B-pinan-3-yl-9-borabicyclo[3.3.l]nonane (Alpine-Borane) could reduce deuterioaldehydes in excellent enantiomeric excess (Figure 14.9). Unfortunately this reagent did not demonstrate the same outcome when applied to ketones. 

Another approach in the search for useful chiral reducing agents has been the derivatization of borane and boron hydrides [110, 111, 114]. Some of the most successful chiral reagents based on boron are those derived from the hydroboration of a-pinene, which is conveniently available in both enantiomeric forms (Scheme 2.22). Midland reported that the hydroboration product of a-pinene with 9-BBN, a reagent that subsequently came to be known as Alpine-Borane (179), is superb in the enantioselective reduction of aiyl alkynyl ketones [124]. He showcased the use of Alpine-Borane in the context of an enantioselective synthesis of Prelog-Djerassi lactone 181... 

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