Hydroalumination/iodination

Steps including hydroxy directed alkyne hydroalumination-iodination... 

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. 

This method was employed in the stereospecific construction of a silyl diene in a synthesis of chlorotri-cholide (Scheme 2.80). The boronic acid partner 2.233 was prepared by hydroboration and hydrolysis. The vinyl iodide was 2.235 prepared by hydroalumination-iodination. The silyl group was included in order to boost stereoselectivity in the later Diels-Alder reaction, but also served to facilitate the synthesis of the vinyl iodide coupling partner. The Suzuki coupling yielded the diene 2.236 with retention of the stereochemistry of both alkenes. Thallium hydroxide was employed as the Lewis base. Thallium-containing Lewis bases have been found to be advantageous in a number of cases, but the toxicity of thallium is a serious concern. 

Let s start with a synthesis of racemic S-deoxy-VGEi (90) developed by the Sih group at the University of Wisconsin. The key reaction was the addition of vinyllithium 88 to the THP ether derived from enone 86. The vinyllithium reagent was prepared by hydroalumination-iodination of I-octyne (87) followed by a transmetallation. Enone 86 was prepared in two steps from cyclopentadiene and ethyl 7-bromoheptanoate. Notice that the alkylation of lithium cyclopentadienide with this bromoester provided I-substituted cyclopentadiene 84 in quantitative yield. The isomerization that had to be avoided in the Corey lactone approach was a necessary part of these tactics. 

Hydroalumination. Titanocene dichloride is an effective catalyst for hydro-uluminution of alkenes and alkynes with his(dialkylamino)alancs5 and various complex aluminum hydrides. The adducts can be quenched with water or iodine. The reaction is satisfactory for terminal alkenes and internal alkynes, but is not clcun for internal alkenes and terminal alkynes. 

For the synthesis of flavocristamide A (160), ( >iodoalkene (I) was necessary. This was prepared from 9-decen-l-ol (F). Chain elongation of F yielded G, whose double bond was converted to a triple bond to give H. Subsequent hydroalumination of H was followed by quenching with iodine to give the desired iodoalkene I. 

Metallated acetylenes, obtained by hydrozirconation, hydroalumination or hydroboration, react with elemental iodine to give ( )-iodoalkene. Terminal alkynes 229 (R = octyl or decyl) add hydrogen iodide, generated from the boron triiodide/A,A-diethylaniline complex and acetic acid, in a Markovnikov sense to afford the iodoalkenes 230. cw-Addition of hydrogen iodide, produced in situ from trimethylsilyl chloride and aqueous sodium iodide, to a number of internal alkynes has been reported... 

In contrast to the reaction with diisobutylaluminium hydride, hydroalumination of disubstituted alkynes with lithium hydridodiisobutylmethylaluminate, obtained from diisobutylaluminium hydride and methyllithium, results in anti addition across the triple bond. Subsequent reaction with aldehydes gives allylic alcohols, with CO2 gives a,p-unsaturated acids and with iodine gives alkenyl iodides, isomeric with the products obtained in the reaction sequences using diisobutylalvmiinium hydride. ... 

Alkenyl iodides can be generated in situ by hydroalumination of alkynes, followed by iodination, and a,jS-unsaturated esters are prepared by carbonylation without isolation of the iodide. As an example, the propargylic alcohol 10 was aluminated regio- and stereoselectively and converted to the alkenyl iodide 11. The intramolecular carbonylation of 11 afforded the dibutenolide 12 in 81 % yield. The reaction is a key step in the total synthesis of (-l-)-parviflorin [9]. 

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