Hydroboration. Carreira: Chapter 7

Transcription

1 ydroboration Carreira: Chapter 7 ydroboration of alkenes/alkynes is one of the most versatile reactions available. Most commonly, the resulting alkyl borane intermediates are not isolated, but are used in subsequent reactions for forming a wide range of functional groups. C Most examples that will be shown will involve oxidation to the alcohol Na, or 4 N or Na or 1 NS 3 N 1 1 or 1 Monograph: rown,. C. rganic Synthesis Via oranes; Wiley: New York, 1975; rown,. C. rganic Synthesis Via oranes Volume ; Aldrich Chemical Company: Milwaukee, WI, 001.

2 Many Different eagents There are several reagent options available depending on selectivity/reactivity concerns. Generally, boranes ( compounds) can be prepared easily from inexpensive reagents. Many are air and moisture sensitive. Most are prepared by initial hydroboration of a different olefin with borane ( 3 ). ( equiv) the addition of the first two alkyl groups is usually rapid Some Commonly used hydroborating agents 3 S (MS, air stable, neat liquid, ~10 M) diisoamylborane (Sia ) thexylborane (Thx ) 1 (substrate) 1 the addition of the third alkyl group is slower and quite dependent on the substitution pattern of the olefin 9-borabicyclo-[3.3.1]nonane (9-N) di(isopropylprenyl)borane (ipp ) useful for catalytic pinacolborane (Pin) catecholborane (Cat)

3 Stereoselectivity With Acyclic lefins ydroboration involves a four-membered transition state with syn-addition across the alkene/alkyne. Conversion of C into C is stereospecific with retention of configuration. The boron usually ends up on the less substituted end of the olefin. trisubsubstituted olefins similar arguement can be made for disubstituted, but regioselectivity now becomes important. L M / L M / L M / M potential A 1, interactions L preferred L L L L M potential A 1,3 interactions M M M interaction of M with boron ligands overrules any A 1, but with 3, A 1, will win out

4 Asymmetric ydroboration Asymmetric hydroborations were among the first examples of non-enzymatic transformations to proceed with high enantiomeric excess (J. Am. Chem. Soc. 1961, 83, 486). Several reagents have been developed, but those derived from α-pinene (rown) are still the most widely used. diisopinocamphenylborane sterically demanding reagent, reacts with unhindered alkenes (+)-α-pinene (excess) 91% ee 3 S TF, rt, 16 h crystallize ( )-Ipc > 99% ee (note change in rotation) solid, can be stored at 0 ºC under N J. rg. Chem. 198, 47, 5065 monoisopinocamphenylborane unhindered reagent, reacts will all classes of alkenes (+)-α-pinene (1 equiv) 3 S TF rt, 96 h (+)-Ipc + ( )-Ipc 4.5% 91% 4.5%

5 ( )-Ipc (+)-Ipc Asymmetric ydroboration ( )-Ipc 1,-cis-olefins give high selectivity, others react slowly (+)-Ipc 1,-trans- and trisubstituted olefins give high to moderate selectivity 1,1-disubstituted olefins are still troublesome, with no general reagent available N n 98% ee 4% ee 9% ee 93% ee 99% ee 99% ee 99% ee 83% ee t-u t-u 73% ee 75% ee 9% ee 76% ee 65% ee 53% ee 58% ee 86% ee 66% ee > 99% ee 7% ee ( )-Ipc : J. rg. Chem. 198, 47, 5065; J. Am. Chem. Soc. 1986, 108, 049; J. rg. Chem. 1986, 51, 496 (+)-Ipc : J. rg. Chem. 198, 47, 5074; J. rg. Chem. 1987, 5, 310; J. rg. Chem. 1980, 45, 3543; ull. Chem. Soc. Jpn 1988, 61, 93

6 Conversion to ther rganoboron Compounds oronic acids, boronic esters, and organotrifluoroborates are useful intermediates for cross-coupling and other reactions. Their preparation from alkenes is complicated by needing to perform a monohydroboration with 3. Snieckus and co-workers reported a nice solution to this problem. Mg or Li () 3 then KF boronic acids F 3 K boronic esters potassium trifluoroborates 3 alkene or alkyne aq. C..5 equiv (inexpensive) Angew. Chem. Int. Ed. 003, 4, ipp (similar steric demand & reactivity to Sia ) () () or allylation of C