Crotylboration reagent

Asymmetric Crotylboration . Reagents for crotylboration are prepared from 2,5-dimethyl-S-methoxyborolane (eq 5) by addition of (Z)- or ( )-crotylpotassium under standard conditions. Reactions with representative achiral aldehydes are 93-96% diastereoselective and 86-97% enantioselective for the major diastereomer (eqs eq 12 and eq 13). Results with chiral aldehydes conform to the rule of double asymmetric synthesis. ... 

As shown in Scheme 17, this alternate approach to 85 woriced beautifully. Thus, adopting an alternate asymmetric reaction as a means to attach the butanone-Iike spacer to 88, this aldehyde was exposed to the indicated (+)-Ipc-derived crotylboration reagent in an event that afforded 133 with complete diastereoselectivity. Subsequent methylation of the newly formed alcohol followed by a Wacker oxidation step then served to create methyl ketone 134. With these steps completing the synthesis of the required four-carbon spacer in 44 % overall yield, the substrate was then treated with LiHMDS and TMSCl to generate a sdyl enol ether (135) in... 

A valuable feature of the Nin/Crn-mediated Nozaki-Takai-Hiyama-Kishi coupling of vinyl iodides and aldehydes is that the stereochemistry of the vinyl iodide partner is reflected in the allylic alcohol coupling product, at least when disubstituted or trans tri-substituted vinyl iodides are employed.68 It is, therefore, imperative that the trans vinyl iodide stereochemistry in 159 be rigorously defined. Of the various ways in which this objective could be achieved, a regioselective syn addition of the Zr-H bond of Schwartz s reagent (Cp2ZrHCl) to the alkyne function in 165, followed by exposure of the resulting vinylzirconium species to iodine, seemed to constitute a distinctly direct solution to this important problem. Alkyne 165 could conceivably be derived in short order from compound 166, the projected product of an asymmetric crotylboration of achiral aldehyde 168. 

Brown s crotylboration protocol was used effectively in the synthesis of azu-mamide A 28. Azumamides are unusual cyclic peptides that show potent inhibitory activity on histone deacetylase enzymes. A highly diastereo- and enan-tioselective (dr >99% 98% ee) crotylation of 3-benzyloxypropanal with the chiral reagent ( >crotyl-1Ipc2borane (l19E) afforded the homoallylic alcohol 29. Subsequent reductive ozonolysis and K2CO3-mediated hydrolysis of the acetate furnished the diol 3016 (Scheme 3.1m). 

Crotylboration of Aldehydes. The crotyl analogs of this reagent (Icr2BCrt) likewise provide very high levels of enantio- and diastereoselectivity (>99% de) when condensed with aldehydes. By varying the geometry of the crotyl group (Z or E) and the (-b)-carene isomer used in the... 

Given this problem, the attachment of the butanone synthon to aldehyde 74 prior to the methyl ketone aldol reaction was then addressed. To ovenide the unexpected. vTface preference of aldehyde 74, a chiral reagent was required and an asymmetric. syn crotylboration followed by Wacker oxidation proved effective for generating methyl ketone 87. Based on the previous results, it was considered unlikely that a boron enolate would now add selectively to aldehyde 73. However, a Mukaiyama aldol reaction should favour the desired isomer based on induction from the aldehyde partner. In practice, reaction of the silyl enol ether derived from 87 with aldehyde 73, in the presence of BF3-OEt2, afforded the required Felkin adduct 88 with >97%ds (Scheme 9-29). This provides an excellent example of a stereoselective Mukaiyama aldol reaction uniting a complex ketone and aldehyde, and this key step then enabled the successful first synthesis of swinholide A. 

By a similar method, the (Z)-crotylborate is synthesized from cA-2-butene in 70-75% yield with a 98% isomeric purity. The tartrate esters of allylboronic acids are an excellent reagent for asymmetric allylboration of carbonyl compounds. Allyl(diisopinocampheyl)borane [51] and the allylic boron derivatives of ester and amide, such as camphordiol [52], pinanediol [53], 1,2-diphenyl-1,2-ethylenediamine [54], have also been successfully used for asymmetric allylboration of carbonyls. 

In Scheme 46, case I is discussed with respect to the crotylboration of (R)-iso-propylidene glyceraldehyde. Altogether 4 diastereomers I to IV may be formed under the influence of the chiral information contained both in the aldehyde and in the crotylboron reagents 46-1 to 46-6 [106,107,108,109]. The simple diaster-eoselectivity, i.e., the relative configuration with respect to C-3/4 is given by the Zimmerman-Traxler closed transition state and is anti for the (E)- and syn for the fZj-crotyl isomers of 46-1 to 46-6. It can be seen from Scheme 46 (sixth col-... 

Reactions of reagents 1 and 2 with metal-complexed aromatic, propargylic and dienylic aldehydes provides homoallylic alcohol products with improved selectivity compared to their uncomplexed counterparts. The reaction of benzaldehyde chromium tricarbonyl complex 14 with (R,R)-1 followed by oxidative decomplexation provided ( -15 in 90% yield and 83% ee. The (JE)-crotylboration of 14 with (R,R)-2 provided 16 in 90% yield and 92% ee. Reaction of aldehyde 14 with (. -crotylboronate 3, however, provided adduct 17 in only 41% ee. 

A quick analysis of 9(S)-dihydroerythronolide A 19 shows that 7 of the 11 stereocenters could be created using reagent control of diastereoselectivity by crotylboration reactions. The stereogenic centers at C6 and C12 having a tertiary alcohol function are presently outside the scope of stereoselective crotylboration reactions. Here we have to rely on other methods. For instance, the use of lactic acid enolates developed by Seebach [28] appeared attractive to generate the tertiary centers both at C6 and Cl2. 

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