Hydroboration Carreira: Chapter 7 Hydroboration 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. OH CO2R R R1 R1 Most examples that R2 R2 will be shown will H H involve oxidation to R1 2 the alcohol NaOH, H2O2 R or Me4NO or NaBO3•H2O H R R H B R R B R R 1 R 1 1 or 1 R2 R R R R2 R2 R2 H H H H2NOSO3H O H O R NH2 R1 R1 or R1 R2 R2 R2 H H H Monograph: Brown, H. C. Organic Synthesis Via Boranes; Wiley: New York, 1975; Brown, H. C. Organic Synthesis Via Boranes Volume 2; Aldrich Chemical Company: Milwaukee, WI, 2001. Many Different Reagents There are several reagent options available depending on selectivity/reactivity concerns. Generally, boranes (B–H 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 (BH3). R R R1 R R R R 1 H (2 equiv) (substrate) R B H B H B H R R R R the addition of the first two the addition of the third alkyl group alkyl groups is usually rapid is slower and quite dependent on the substitution pattern of the olefin Some Commonly used hydroborating agents H useful for Me B catalytic HB Me BH H B O 2 Me B H diisoamylborane O (Sia BH) 9-borabicyclo-[3.3.1]nonane (9-BBN) BH3•SMe2 2 pinacolborane (BMS, air stable, neat (PinBH) liquid, ~10 M) Me Me Me Me Me O H BH2 B H Me BH Me Me 2 O thexylborane di(isopropylprenyl)borane catecholborane (CatBH) (Thx2BH) (iPP2BH) Stereoselectivity With Acyclic Olefins Hydroboration involves a four-membered transition state with syn-addition across the alkene/alkyne. Conversion of C–BR2 into C–OH 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. H B B/O Me Me RM H R B/O R RL R RL R RL R potential 1,2 RL RM Me RM RM R A interactions B/O preferred RL R OH Me Me R potential R 1,3 H RM A interactions RL R RL R RL R H B R Me R OH R OH M M M interaction of RM with boron ligands overrules any A1,2 1,2 • but with BH3, A will win out Asymmetric Hydroboration 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 (Brown) are still the most widely used. diisopinocamphenylborane – sterically demanding reagent, reacts with unhindered alkenes Me Me BH BH3•SMe2 solid, can be stored 2 at 0 ºC under N2 THF, rt, 16 h crystallize (+)-α-pinene (–)-Ipc2BH (excess) > 99% ee J. Org. Chem. 1982, 47, 5065 91% ee (note change in rotation) monoisopinocamphenylborane – unhindered reagent, reacts will all classes of alkenes Me Me Me BH BH BH3•SMe2 2 + 2 THF rt, 96 h (+)-α-pinene (+)-IpcBH2 (–)-Ipc2BH (1 equiv) 4.5% 91% 4.5% Asymmetric Hydroboration Me Me (–)-Ipc2BH – 1,2-cis-olefins give high selectivity, others react slowly BH BH2 (+)-IpcBH – 1,2-trans- and trisubstituted olefins give high to moderate selectivity 2 2 1,1-disubstituted olefins are still troublesome, with no general reagent available (–)-Ipc2BH (+)-IpcBH2 N Me Me Me Me Me Me O O Bn O 98% ee 92% ee 93% ee 99% ee 99% ee 99% ee 83% ee 24% ee Me Me t-Bu Ph Ph Me Me t-Bu Me Ph 73% ee 75% ee 92% ee 76% ee 65% ee Me Ph Me Me Me Ph Me Me Me Me Me Me 53% ee 58% ee 86% ee 66% ee > 99% ee 72% ee (–)-Ipc2BH: J. Org. Chem. 1982, 47, 5065; J. Am. Chem. Soc. 1986, 108, 2049; J. Org. Chem. 1986, 51, 4296 (+)-IpcBH2: J. Org. Chem. 1982, 47, 5074; J. Org. Chem. 1987, 52, 310; J. Org. Chem. 1980, 45, 3543; Bull. Chem. Soc. Jpn 1988, 61, 93 Conversion to Other Organoboron Compounds Boronic 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 BH3. Snieckus and co-workers reported a nice solution to this problem. OR B(OMe)3 ROH RMg or RLi R B boronic esters then H2O OH OR R B OH H2O KHF2 R BH boronic acids R BF K potassium 2 3 trifluoroborates alkene or BH3 alkyne aq. CH2O H B R B R B OH 2.2–2.5 equiv (inexpensive) iPP2BH allylation of CHO (similar steric demand & reactivity to Sia2BH) H2O or ROH R B(OH)2 O R B(OR)2 R B Angew. Chem. Int. Ed. 2003, 42, 3399. OH.