Borane, derivatives hydroboration

Mono- and diaLkylboranes obtained by controlled hydroboration of hindered olefins and by other methods can serve as valuable hydroborating agents for more reactive olefins. Heterosubstituted boranes are also available and used for this purpose. These borane derivatives show differences in reactivity and selectivity. 

WitlUiindered alkenes, it is more difficult to add three a.kenes to borane. This becomes the basis for unique, borane derivatives. Sw Hydroboration Reagents. 

Asymmetric Hydroboration. Rhodium complexes are known to catalyze hydroboration of alkenes with unreactive borane derivatives, e.g. catecholborane and oxaborolidine. This reaction proceeds enantioselectively by use of BINAP as a ligand for neutral " or cationic rhodium complexes. Reaction of styrene with catecholborane followed by oxidation affords (R)-1-phenylethanol in 96% ee in the presence of (R)-BINAP and [Rh(cod)2]Bp4 (eq 5). ... 

A different style of reduction comes with the use of trialkyl boranes derived from a-pinene. Hydroboration of a-pinene 22 occurs from the less hindered face away from the gem-dimethyl groups to give the tertiary borane 23 with the usual regioselectivity (chapter 17). The marked hydrogen atom is transferred from boron to carbon.3... 

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. 

Several mono- and dialkylboranes obtained by controlled hydroboration of olefins are valuable hydroborating agents. Heterosubstituted borane derivatives are also available, and the search for new reagents, including higher boranes, continues . The most frequently used are shown in Fig. 1 where for convenience monomeric forms are presented. 

With this spectrum of reagents, virtually all unsaturated hydrocarbons can be hydroborated. Moreover, many functional groups are tolerated in hydroboration with substituted borane derivatives, since double and triple C—C bonds react more rapidly than most other functionalities (see Table 1). Only aldehydes, ketones and carboxylic groups must be protected. Consequently, for the first time, functionalized organometall-ics are available. Chiral organoboranes of high optical purity can be prepared ... 

The above inconveniences are circumvented by the application of substituted borane derivatives, e.g., Sia2BH and 9-BBN (see Fig. 1 for definitions), which react with high regioselectivity and sensitivity to steric factors. Thus, 1-alkenes and 1-alkynes are hydroborated at the terminal position. The internal unsymmetrically disubstituted alkenes are also selectively hydroborated. The clean transformation of 1-alkynes into vinylboranes—not possible with borane—can be achieved with these reagents (Fig. 2). 

Organoboranes possessing one B—C bond in the molecule can also be obtained by hydroborating alkenes and alkynes with heterosubstituted borane derivatives, especially dihalogenoboranes, which can be stabilized by complexation with amines, phosphines, ethers and sulfides. The last two are useful complexing agents for both the preparation and the reactions of dihalogenoboranes . The most convenient synthesis of dichloroborane etherate is the reaction of LiBH. with BCl, in Et,0 ... 

The trialkylborane is derived from monoalkyl-(l,l,2-trimethylpropyl)borane by hydroboration. Care must be taken in the oxidation step leading to the a-chiral ketones and buffering is necessary to avoid racemization. However, even with these precautions, 2-6% racemization is observed in some cases9,20. The intermediate alkenyl-(l,l,2-trimethylpropyl)borinates are relatively resistant to oxidation thus prolonged reaction times or higher temperatures are sometimes required to complete the reaction via the haloalkyne route. 

Hydroboration of 2-[2-(ben7yloxy)ethyl]-6,6-dimethylbicyclo[3.1.1]hept-2-ene (the benzyl ether of nopol) with 9-BBN produces a reagent comparable to the borane derived from (—)-a-pinene (vide supra)11. This reagent is available from Aldrich under the trade name NB-Enantrane. 

Coupling reactions of alkyl boranes, formed by hydroboration of alkenes, with unsaturated halides (or triflates or phosphonates) is possible, and this reaction is finding increasing use in synthesis. For example, coupling of the alkyl borane derived from hydroboration (with 9-borobicyclo[3.3.1]nonane, 9-BBN) of the alkene 200 with the alkenyl iodide 201 gave the substituted cyclopentene 202, used in a synthesis of prostaglandin Ei (1.205). This type of B-alkyl Suzuki coupling reaction is very useful for the synthesis of substituted alkenes. 

Halogenated boranes react with the usual regioselectivity, with addition of the boron atom to the less-substituted end of the carbon-carbon double bond, although they do not always show the same reactivity as other borane derivatives. For example, the far higher reactivity of dibromoborane towards more-substituted alkenes, in contrast to disiamyborane, makes possible the selective hydroboration of the double bonds in 2-methyl-1,5-hexadiene (5.11). 

Moreover, the polyfunctional nature of BHj, its relative low selectivity and its low steric requirements cause various difficulties. To overcome these problems, various types of borane derivatives have been developed [2]. The regioselectivity [2] of addition of these boranes to an alkene is dependent on both steric and electronic effects exerted by the substituents present on C=C and also on the bulkiness of the hydroborating agent [3],... 

A number of less hindered monoalkylboranes is available by indirect methods, eg, by treatment of a thexylborane—amine complex with an olefin (69), the reduction of monohalogenoboranes or esters of boronic acids with metal hydrides (70—72), the redistribution of dialkylboranes with borane (64) or the displacement of an alkene from a dialkylborane by the addition of a tertiary amine (73). To avoid redistribution, monoalkylboranes are best used /V situ or freshly prepared. However, they can be stored as monoalkylborohydrides or complexes with tertiary amines. The free monoalkylboranes can be hberated from these derivatives when required (69,74—76). Methylborane, a remarkably unhindered monoalkylborane, exhibits extraordinary hydroboration characteristics. It hydroborates hindered and even unhindered olefins to give sequentially alkylmethyl- and dialkylmethylboranes (77—80). 

Among chiral dialkylboranes, diisopinocampheylborane (8) is the most important and best-studied asymmetric hydroborating agent. It is obtained in both enantiomeric forms from naturally occurring a-pinene. Several procedures for its synthesis have been developed (151—153). The most convenient one, providing product of essentially 100% ee, involves the hydroboration of a-pinene with borane—dimethyl sulfide in tetrahydrofuran (154). Other chiral dialkylboranes derived from terpenes, eg, 2- and 3-carene (155), limonene (156), and longifolene (157,158), can also be prepared by controlled hydroboration. A more tedious approach to chiral dialkylboranes is based on the resolution of racemates. /n j -2,5-Dimethylborolane, which shows excellent enantioselectivity in the hydroboration of all principal classes of prochiral alkenes except 1,1-disubstituted terminal double bonds, has been... 

The hexabutenylbenzene complex reacts with Br2 to give the dodecabromo-derivative, with bulky silanes and boranes to give regiospecific hydrosilylation and hydroboration (Scheme XII). 

The dominant factors reversing the conventional ds-hydroboration to the trans-hydroboration are the use of alkyne in excess of catecholborane or pinacolborane and the presence of more than 1 equiv. of EtsN. The P-hydrogen in the ris-product unexpectedly does not derive from the borane reagents because a deuterium label at the terminal carbon selectively migrates to the P-carbon (Scheme 1-5). A vinylidene complex (17) [45] generated by the oxidative addition of the terminal C-H bond to the catalyst is proposed as a key intermediate of the formal trans-hydroboration. 

The adducts derived from catechol borane are hydrolyzed by water to vinylboronic acids. These materials are useful intermediates for the preparation of terminal vinyl iodides. Since the hydroboration is a syn addition and the iodinolysis occurs with retention of the alkene geometry, the iodides have the -configuration.214... 

This type of reaction is known as hydroboration, and it was exploited by H. C. Brown as a route to organic derivatives of the boranes. 

In comparison with the hydroboration and diborafion reactions, thioboration reactions are relatively limited. In 1993, Suzuki and co-workers reported the Pd(0)-catalyzed addition of 9-(alkylthio)-9-BBN (BBN = borabicyclo [3.3.1] nonane) derivatives to terminal alkynes to produce (alkylthio)boranes, which are known as versatile reagents to introduce alkylthio groups into organic molecules [21], Experimental results indicate that the thioboration reactions, specific to terminal alkynes, are preferentially catalyzed by Pd(0) complexes, e.g. Pd(PPh3)4, producing (thioboryl)alkene products, in which the Z-isomers are dominant. A mechanism proposed by Suzuki and co-workers for the reactions involves an oxidative addition of the B-S bond to the Pd(0) complex, the insertion of an alkyne into the Pd-B or Pd-S bond, and the reductive elimination of the (thioboryl)alkene product. 

Scheme 3.2-27. Combined hydroboration and Et2BH-catalyzed condensation of diethyl(propyn-l-yl)borane (via 29) and (Z) bis(diethylboryl)alkenes lead to the 2,3,5-tricarba-n/do-hexaborane(7) derivatives 55...

It is a striking feature of metal-catalyzed hydroboration that alkoxyboranes are more effective than borane or its alkyl derivatives. Analysis of the electronic features of the two classical reagents, catecholborane and 9-BBN, reveal only modest differences in the B-H region (Fig. 2.3). This by itself does not explain the narrow convergence of... 

Various prochiral olefins are hydroborated by Rh complexes of BINAP or DIOP in up to 96% optical yield (30h, 31). Oxidation of the products provides a convenient way to produce optically active alcohols. Reaction of styrene and catecholborane in the presence of a BINAP-Rh complex at low temperature forms, after oxidative workup, 1-phenylethyl alcohol in 96% ee (Scheme 11) (31). Double stereodifferentiation occurs in the BINAP-Rh catalyzed reaction of 4-methoxy-styrene and an ephedrine-derived chiral borane (32). 

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