Hydroalumination stereoselectivity

Alkynes are much more reactive toward hydroalumination than alkenes. Hence, they readily react with both dialkylaluminum hydrides and LiAlH4 under mild conditions in the absence of a catalyst [1]. However, it is not always possible to avoid side reactions and subsequent transformation of the vinylalanes formed in this transformation [81, 82]. In addition, ds-trans-isomerization of the metallated C=C bond can take place, thereby reducing the stereoselectivity of the overall reaction [83]. 

This chapter has been organized into three sections. The first section deals with transition metal-catalyzed hydroboration in organic synthesis and this is divided into three subsections - mechanism, chemoselectivity, and stereoselectivity. The second section deals with the application of transition metal-catalyzed hydroalumination reactions in organic synthesis, and this is also divided into three subsections - mechanism, chemoselectivity, and stereoselectivity. The third section examines the application of both hydroborations and hydroaluminations in total synthesis. 

Lautens also used this nickel-catalyzed hydroalumination methodology in the total synthesis of ionomycin 145. The starting compound was a [3.2.1]oxabicyclic alkene 143.144 Their rigid bicyclic structures can be used to introduce functional groups in a highly stereoselective manner. The synthesis of the key intermediate 144 involves the slow addition of DIBAL to the oxabicyclic alkene and the Ni(COD)2/(6T)-BINAP in toluene to afford 144 in 95% yield and 93-95% ee. (Scheme 18). 

E)-Allylsilanes These silanes can be prepared regio- and stereoselectively by hydroalumination of (chloromethyl)dimethylsilyl-l-alkynes (1) to give the cis-adduct 2. Reaction of CH3Li (3 equiv.) with 2 results in (E)-allyltrimethylsilanes (3). 

Hydrido(trialkylsilyl)silyllithiums, preparation, 3, 424 Hydroacylations, olefins, 10, 142 Hydroalkoxylations and etherification, 10, 672 in etherification, 10, 683 Hydroaluminations for C-E bond formation characteristics, 10, 857 chemoselectivity, 10, 859 mechanism, 10, 858 overview, 10, 839-870 stereoselectivity, 10, 861 total synthesis applications, 10, 865 characteristics, 3, 275 process and examples, 9, 268 via Ti(IV) complexes, 4, 658 Hydroaminations actinide-catalyzed, 4, 237 in aminations... 

Hydroboration proceeds without a catalyst, but hydroboration with less active catecholborane (225) is accelerated by catalysts. Usually 1,2-addition to conjugated dienes takes place, but the Pd-catalysed reaction of catecholborane (225) gives the 1,4-adduct 226. This reaction is not catalysed by Rh complexes [98], Hydroalumination of conjugated dienes catalysed by Cp2TiCl2 affords the allylic aluminium compounds 227 by 1,4-addition. The Pd-catalysed hydrostannation of isoprene with HSnBu3 affords the (Z)-2-alkenylstannane 228 with high regio- and stereoselectivities [99],... 

In this synthesis (Scheme 6), the C2-symmetri-cal triacetonide of D-mannitol (32) is converted via the epoxide 33 and its nucleophilic addition product 34 to the propargylic alcohol derivative 35. From this intermediate, the Z-configured vinyl iodide 36 is stereoselectively obtained by hydroalumination/iodination. The Pd-catalyzed Heck cyclization then affords the isomerically pure product 37, which represents a potential building block for the synthesis of la,2y5,25-trihy-droxy-vitamin D, following the classical Wittig strategy of Lythgoe. 

An approach amenable to the preparation of various fused selenophenes and benzo[3]selenophenes involves the treatment of 1,4-dilithiated intermediates with bis(phenylsulfonyl)selenide 112 <1994CPB1437>. The synthetic sequence to the selenolo[2,3-/ ]selenophene 113 from 3-ethynylselenophene 110 is shown in Scheme 11 <1997H(45)1891>. A stereoselective hydroalumination of 110 with diisobutylaluminium hydride (DIBAL-H) followed by bromination with NBS gave dibromo compound 111. Dilithiation of 111 followed by treatment with selenium electrophile 112 gave 113. 

Dienes.1 (E)-l-Alkenylalanes, readily obtained by hydroalumination of 1-al-kynes,2 couple with vinyl iodides in the presence of this Pd(0) catalyst and zinc chloride to give 1,3-dienes with retention of the configuration. Alkenylzinc derivatives may be the actual reactants. Nickel catalysts are less stereoselective than palladium-phosphine catalysts. 

Hydroalumination of 1-chloro-l-alkynes. Lithium aluminum hydride adds to 1-chloro-l-alkynes (1) regio- and stereoselectively to form the a-chlorovinyl alanates 2, which are moderately stable at 0°C. On methanolysis they are converted into (E)-l-chloro-l-alkenes (3). They can also be converted into (Z)-l-bromo-l-chloro-l-alkenes (5) and into (Z)-l-chloro-l-iodo-l-alkenes (6). 

From all available evidence it is reasonable to conclude that the hydroalumination of both alkenes and alkynes by R2AIH occurs in a kinetically controlled syn manner and that any anti adduct formed results from a subsequent isomerization to the more stable configuration. In many situations the syn adduct can be isolated or detected prior to isomerization and its conversion to the anti adduct monitored. " In Table 5 are summarized the stereoselectivities observed in the hydroaluminations of a spectrum of substituted alkynes under various conditions. It is noteworthy that the thermal isomerization of the syn adduct can proceed with remarkable facility (at 0 °C) when a TMS or MesGe group is attached to the C=C linkage. 

Table 5 Stereoselectivities Observed in the Hydroalumination of Heterosubstituted Alkynes by...

Once the hydroalumination adducts of C=C and C C bonds have been cleanly formed, protolysis or oxidation can produce useful derivatives. With H2O or O2, generally all available C—Al bonds are destroyed. Protolysis or deuteriolysis of such adducts constitutes an overall reduction or deuteriating reduction of the original C—C unsaturation (equations 13, 39 and 41 Schemes 6-8). ° Any stereoselectivity or regioselectivity of the original hydroalumination is preserved. 

The system CpeTiCle/AlClBu is an efficient reagent for hydroalumination of disubstituted acetylenes in a regio-and stereoselective method for the synthesis of -alkenylchloralanes.1169 The reduction carbonylation of Cp2TiCl2 at room temperature by chloroaluminate molten salts or ionic liquids has been reported.1170... 

Hydroalumination of alkynes has been well investigated and has provided a very convenient way of synthesizing vinylaluminum species stereoselectively (Scheme 6.131). A general reaction sequence can be used to prepare either or Z alkenes. The pro-... 

The transformation of the a-oxoketene dithioketals 3.227 is especially interesting. Reduction by LAH in THF at room temperature leads to allylic alcohols, while under reflux, the hydroalumination of the double bond also takes place. This reaction can be stereoselective [GB2, RCl] (Figure 3.87). NaBH4 in MeOH gives allylic alcohols, while DIB AH leads to the corresponding saturated ketones [RCl]. 

The reaction of dialkylaluminum hydrides with mono- or di-substituted acetylenes provides the best route to alkenyldialkylaluminums . The hydroalumination of acetylene itself gives polymers Monohydroalumination of terminal acetylenes can be conducted either neat or in hydrocarbon solvents (< 50°C). The products are (E)-alkenylalanes as the result of a regio and stereoselective cis addition of Al—H to the C=C bond i- ... 

Hydroalumination followed by protonolysis is less convenient for stereoselective cis hydrogenation of the double bond. Simple, vicinally disubstituted double bonds sluggishly undergo hydroalumination and the carbon-aluminum bond undergoes inversion in hydrocarbon solvents at moderate temperatures. Strained olefins are more reactive and can react stereoselec-tively under carefully controlled conditions126. 

Hydroaluminadon. A stereoselective approach to cycloheptenols is based on the cleavage of 8-oxabicyclo[3.2.1]oct-6-enes. The lack of generality for the fragmentation protocol plagued the method. Now a useful procedure consists of Nilcodl -catalyzed hydroalumination and treatment of the alane with i-BUjAlCl. This method is also appropriate for the asymmetric synthesis of cyclohexenols. 

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