Intramolecular hydroboration

In a concise formal total synthesis of strychnine, the cyclophane 108 was prepared in 65% yield by applying the hydroboration-intramolecular coupling method to 107 under high dilution conditions, and converted to the pentacycle 109 by transannular inverse-electron-demand Diels-Alder reaction [88]. 

High levels of asymmetric induction have been achieved in the hydroboration of 1,3-, 1,4-, and 1,5-dienes with thexylborane (482,483,489,490). The first chiral center is formed by an intermolecular reaction. In the second step, the organoborane intermediate undergoes an intramolecular hydroboration, creating the second chiral center with high diastereoselectivity. 

The reverse reaction (formation of metal alkyls by addition of alkenes to M-H) is the basis of several important catalytic reactions such as alkene hydrogenation, hydroformylation, hydroboration, and isomerization. A good example of decomposition by y3-elimination is the first-order intramolecular reaction ... 

Intramolecular Suzuki reactions have been done by hydroboration followed by... 

Section B of the Scheme 9.1 shows several procedures for the synthesis of ketones. Entry 6 is the synthesis of a symmetrical ketone by carbonylation. Entry 7 illustrates the synthesis of an unsymmetrical ketone by the thexylborane method and also demonstrates the use of a functionalized olefin. Entries 8 to 10 illustrate synthesis of ketones by the cyanide-TFAA method. Entry 11 shows the synthesis of a bicyclic ketone involving intramolecular hydroboration of 1,5-cyclooctadiene. Entry 12 is another ring closure, generating a potential steroid precursor. 

Another synthesis of P-D lactone that is based on an enantiomerically pure starting material is shown in Scheme 13.35. The stereocenter in the starting material is destined to become C(4) in the final product. Steps A and B served to extend the chain to provide a seven-carbon 1,5-diene. The configuration of two of the three remaining stereocenters is controlled by the hydroboration step, which is a stereospecific syn addition (Section 4.5.1). In 1,5-dienes of this type, an intramolecular hydroboration occurs and establishes the configuration of the two newly formed C—B and C—H bonds. 

The exhaustive hydroboration of Cig-hexaquinacene (810) has been investigated and the isomeric exo -triols 816 and 817 isolated Also, diketone 809 has been functionalized as in 818a and 818b, but these epoxides resisted intramolecular cyclization . ... 

Similarly, while exploring a route toward the synthesis of strychnine, Bodwell and Li reported hydroboration of i f-[2-(l-allyl-17/-indol-3-yl)ethyl]-6-iodopyridazin-3-amine 184 followed by intramolecular Suzuki reaction (Scheme 45) <2002AGE3261>. 

Stereoselective cyclic hydroboration. The hydroboration of l,4 and 1,5-dienes with thexylborane generally results in boracycles.2 If the intial hydroboration produces an asymmetric center, the second intramolecular hydroboration can be effected with remote asymmetric induction. Thus hydroboration of the diene 1 with thexylborane (1.25 equivalent) followed by oxidation results in a 6 1 mixture of the diastereomers 2 and. 3. An even higher induction is obtained in the case of the 1,4-... 

A characteristic transformation of nonconjugated dienes is their hydroboration to form boraheterocycles.369 For example, the favored hydroborating agent, 9-BBN, is synthesized in such cyclization reaction370,371 (Scheme 6.6). An approximately 1 3 mixture of 1,4- and 1,5-addition products is formed in a second, intramolecular hydroboration step. The 1,4-addition product (40), however, can be readily isomer-ized under mild conditions (65°C, 1 h) through a dehydroboration-hydroboration step to yield pure 9-BBN. 

Primary alkylboranes derived by hydroboration of terminal alkenes with 9-BBN-H are coupled with aryl and alkenyl triflates and halides under properly selected conditions. The reaction proceeds smoothly without elimination of /1-hydrogen using PdCTklppf) or Pd(Ph3P)4 and K3PO4 in dioxane or DMF [132]. The intramolecular cross-coupling of the alkenyl triflate with the alkylborane in 292, prepared by in situ hydroboration of the double bond in 291 with 9-BBN-H, is applied to the annulation to... 

Organoboranes are used for ketone synthesis under basic conditions. The cyclic ketone 482 is prepared from alkenyl iodode 479. Hydroboration of terminal double bond, followed by carbonylation generates 480, and the cyclic ketone 482 is formed by intramolecular transmetallation of 480 to afford 481 [236],... 

Intramolecular hydroboration of allyl vinyl ethers.1 The hydroboration and subsequent oxidation of allyl vinyl ethers 1 with ThxBH2 (2 equiv.) leads to 1,3-diols with almost exclusive syn selectivity. High syn selectivity obtains regardless of the bulk of R1, but is lowered when R is phenyl. Apparently, electronic effects of R1 are important for stereoselectivity. 

Hydroboration-reduction of enones.2 Hydride reduction of a carbonyl group can be used to induce asymmetric intramolecular hydroboration of a double bond via a cyclic transition state. Thus reaction of the enone 1 with thexylborane (1 equiv.) followed by oxidation provides the 1,5-diol 2 with high 1,4-syn selectivity. A similar reaction with the homologous enone provides a 1,6-diol with modest 1.5-syn selectivity (syn anti = 6.6 1). 

It is also possible to achieve remarkable intramolecular remote C-H activation of sterically hindered tetrasubstituted olefins such as 50 (Scheme 9) [8, 9] The initial hydroboration of 50 leads to 51, which gives regio- and stereoselectively the six-membered intermediate organoborane 52, via a C-H insertion reaction (40 °C, 72 h). After oxidation, the diol 53 is obtained in 90% yield as only one diastereo-... 

The palladium-catalyzed hydroboration of allyl phenyl ether 456 is followed by cyclization of the corresponding triflate to afford the chroman core of the tocopheryls 457 (Equation 186) <1998JA9074>. The intramolecular hydroarylation of l-(but-3-enyloxy)-3,5-dimethylbenzene to afford 4,5,7-trimethylchroman can be accomplished using a RuCh/AgOTf catalytic system (Equation 187) <20040L581>. 2,2-Dimethylchromans 458 are formed by a Mo(CO)6 catalyzed intramolecular cyclization of aryl prenyl ethers 459 (Equation 188) <1998S256>. 

An iridium(m) hydride catalyzed intramolecular alkyne hydroalkoxylation can be used to construct isochromans 545 bearing a C(3)-spiroacetal moiety (Equation 226) <2005OL5437>. Novel isochromans bearing an array of C(3)-spiroacetal moieties are accessible via the hydroboration of alkynediols with disiamylborane followed by treatment of the resulting alkenylboron compounds with alkaline hydrogen peroxide <1998CL81>. 

Pyrrolidines are an important class of five-membered heterocycles with noteworthy biological properties [46]. In addition to pharmaceutical applications, the pyrrolidine moiety has also been widely used as a chiral auxiliary for asymmetric synthesis [47]. Although many elegant syntheses of chiral nonracemic pyrrolidines have been reported within the past decade or so [48-50], an alternative approach based on the intramolecular reaction of an azide and organoborane has been developed very recently [51-53], This approach utilizes the hydroboration-azide alkylation tandem reaction as a key sequence, taking advantage of the efficient stereocon-trolled steps. Scheme 20 shows an application of the synthesis of 3-substituted 5-(2-pyrrolidinyl)isoxazole which has been found to have nanomolar activity, comparable to (5)-nicotine, against whole rat brain [54]. 

The starting material for the present synthesis was Wieland-Miescher ketone (24), which was converted to the known alcohol (25) by the published procedure [10], Tetrahydropyranylation of alcohol (25) followed by hydroboration-oxidation afforded the alcohol (26), which on oxidation produced ketone (27). Reduction of (27) with metal hydride gave the alcohol (28) (56%). This in cyclohexane solution on irradiation with lead tetraacetate and iodine produced the cyclic ether that was oxidized to obtain the keto-ether (29). Subjection of the keto-ether (29) to three sequential reactions (formylation, Michael addition with methyl vinyl ketone and intramolecular aldol condensation) provided tricyclic ether (30) whose NMR spectrum showed it to be a mixture of C-10 epimers. The completion of the synthesis of pisiferic acid (1) did not require the separation of epimers and thus the tricyclic ether (30) was used for the next step. The conversion of (30) to tricyclic phenol (31) was... 

In reactions with polymer-bound catalysts, a mass-transfer limitation often results in slowing down the rate of the reaction. To avoid this disadvantage, homogenous organic-soluble polymers have been utilized as catalyst supports. Oxazaborolidine 5, supported on linear polystyrene, was used as a soluble immobilized catalyst for the hydroboration of aromatic ketones in THF to afford chiral alcohols with an ee of up to 99% [40]. The catalyst was separated from the products with a nanofiltration membrane and then was used repeatedly. The total turnover number of the catalyst reached as high as 560. An intramolecularly cross-linked polymer molecule (microgel) was also applicable as a soluble support [41]. 

The reactivity and selectivity of cycloaddition can be considerably increased in intramolecular versions. The protocol was first demonstrated in the Diels-Alder reaction between anthrone 253416,417 and 4-hydroxy-2-butenoate mediated by phenylboronic acid (Equation (73)).418,419 Another method developed for the intramolecular cycloaddition is the synthesis of trienylboranes 256 by hydroboration of terminal alkynes (Equation (74)).419-422... 

Two dialkyl boranes arc in common use. The bicyclic 9-borabicyclo[3.3.1] nonane (9-BBN), introduced in Chapter 34 as a reagent for diastereoselcctive aldol reactions, is a stable crystalline solid. This is very unusual for an alkyl borane and makes it a popular reagent. It is made by hydroboration of cyclo-octa-1,5-diene. The second hydroboration is fast because it is intramolecular but the third would be very slow. The regioselectivity of the second hydroboration is under thermodynamic control. 

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