Aldehydes crotylation

Allylic chromium species can also add to aldehydes. In this regard, an efficient catalytic enantioselective variant using allylic halides as substrates and manganese as co-oxidant has been described recently (Eq. 117). This method provides high enantiomeric excesses in the simple allylation of a wide range of aliphatic, aromatic, and heteroaromatic aldehydes. Crotylation examples are also very enantioselective, albeit with modest anti/syn diastereoselectivity. 

Kim H, Ho S, Leighton XL. A more comprehensive and highly practical solution to enantioselective aldehyde crotylation. J. Am. Chem. Soc. 2011 133 6517-6520. 

It is noteworthy that even a separate treatment of the initial data on branched reactions (1) and (2) (hydrogenation of crotonaldehyde to butyr-aldehyde and to crotyl alcohol) results in practically the same values of the adsorption coefficient of crotonaldehyde (17 and 19 atm-1)- This indicates that the adsorbed form of crotonaldehyde is the same in both reactions. From the kinetic viewpoint it means that the ratio of the initial rates of both branched reactions of crotonaldehyde is constant, as follows from Eq. (31) simplified for the initial rate, and that the selectivity of the formation of butyraldehyde and crotyl alcohol is therefore independent of the initial partial pressure of crotonaldehyde. This may be the consequence of a very similar chemical nature of both reaction branches. 

Coumalic acid, 56, 51 Crotyl fluoride, 57,73 18-CROWN-6,57, 30 Curtius rearrangement, 59, 1 Cyanide ion, as catalyst for conjugate addition of aldehydes, 59, 56 p-Cyanobenzenesulfonyl cyanide, 57, 89 2-( 1 -Cyanocyclohexyljhydrazinecarboxylic acid methyl ester, 58,102 Cy a noferrocene, 56, 30 Cyanogen chloride, 57, 88... 

Reisse used activated zinc for aqueous Barbier-type reactions.66 Submicromic zinc powder produced by pulsed sono-electroreduction is about three times more effective than the commercial variety. The stereochemical course of the allylation and propargylation of several aldehydes with crotyl and propenyl halides using zinc powder as the... 

An efficient route for the synthesis of the Phe-Phe hydroxyethy-lene dipeptide isostere precursors utilized for the design of potential inhibitors of renin and HIV-protease was developed. The key step is the zinc-mediated stereoselective allylation of A-protected a-amino aldehydes in aqueous solution (Eq. 8.32).70 NaBF4/M (M = Zn or Sn) showed facilitating allylation of a variety of carbonyl compounds in water, and a-and y-addition products of crotylations could be alternatively obtained under the control of this novel mediator (Eq. 8.33).71... 

The multi-component procedure is also effective for the chromium-catalyzed addition of organic halides to aldehydes (the Nozaki-Hiyama-Kishi reaction) [73]. The active Cr(II) species is recycled by redox interaction with Mn powder as the stoichiometric co-reductant in the presence of MesSiCl (Scheme 34), which mainly liberates the chromium catalyst from the alkoxide adduct. The chemo- and diastereo-selective addition reaction is performed with a variety of organic halides and alkenyl triflates. In the case of crotyl bromide, the addition is highly stereoconvergent, i.e., the respective anti-... 

Mild allylic oxidation of the A-2-crotyl-substituted thiadiazolidinone 1,1-dioxide 140 by sodium metaperiodate/ ruthenium trichloride hydrate (RuC13) gave the aldehyde 141. Excess oxidizing agent afforded the carboxylic acid 142 (Equation 26) <1999EJ02275>. 

Durandetti et al. have described iron-catalyzed electrochemical allylation of carbonyl compounds with allylic acetates (Equation (27)).333 In the case of aldehydes, slow addition of the corresponding aldehyde is required in order to avoid pinacol formation. With crotyl acetate (R3 = Me), the reaction proved to be highly regioselective, providing almost exclusively branched homoallylic alcohols 150. 

In the reaction of (R,R)-tartrate allyl-boronate with aldehydes, Si attack of the nucleophile on the carbonyl group has been observed, while Re attack occurs in (S, S )-tartrate allyl-boronate reactions. Thus, an (S )-alcohol is produced preferentially when an (R,R)-allyl reagent is used, and the (R)-product can be obtained from an (S.Sj-reagent. assuming that the R substituent in the aldehyde substrate takes priority over the allyl group to be transferred. In fact, no exceptions to this generalization have yet been found in over 40 well-characterized cases where the tartrate auxiliary controls the stereochemical outcome of the allyl or crotyl transfer.72... 

With the aid of BF3 OEt2, methoxyborolane (R,R)-114 reacts with (.E)- or (Z)-crotylpotassium to provide (is,R,R)-115 and (Z,R,R)-115, respectively. After adding the aldehyde to a solution of crotyl-borolane in THF at —78°C for 4 hours, 2-aminoethanol is added. The solution is warmed to room temperature, and oxidative cleavage at this point gives the homoallylic alcohols with high stereoselectivity. The borolane moiety can be recovered by precipitating it as an amino alcohol complex and can be reused without any loss of enantiomeric purity. As shown in Scheme 3-43, the (.E)- and (Z)-crotyl compounds lead to anti- and -products 116, respectively. The diastereoselectivity is about 20 1, and the ee for most cases is over 95% (Table 3-11). 

Treatment of 122 with (R,R)-tartrate crotyl-boronate (E.R.R)-W 1 provides the alcohol corresponding to 123 with 96% stereoselectivity. Benzylation of this alcohol yields 123 with 64% overall yield. The crude aldehyde intermediate obtained by ozonolysis of 123 is again treated with (Z,R,R)-111 (the second Roush reaction), and a 94 5 1 mixture of three diastereoisomers is produced, from which 124 can be isolated with 73% yield. A routine procedure completes the synthesis of compound 120, as shown in Scheme 3-44. Heating a toluene solution of 120 in a sealed tube at 145°C under argon for 7 hours provides the cyclization product 127. Subsequent debromination, deacylation, and Barton deoxygenation accomplishes the stereoselective synthesis of 121 (Scheme 3-44). 

With this method, that is, the reaction of tartaric acid ester-modified crotyl-boronates with chiral 2-methyl aldehydes, the C-19 to C-29 fragment of rifa-mycin has been constructed similarly.76... 

RCp2Ti(crotyl), R = Me, iPr) [13]. Both the regio- and the diastereoselectivity in the allyl-titanation reactions of aldehydes can be explained in terms of a six-membered chair-like transition state (Figure 13.1). 

These c-complexes have been less extensively studied than the r 3-allyltitanium derivatives. r 1 -Allyltitanocenes can readily be prepared from the corresponding magnesium compounds by reaction with Cp2TiCl2 or by reaction of preformed r 3-allyltitanium complexes with but-2-enyl halides [36]. Crotyl-type reagents, which are accessible only in the E-iso-meric form, add to aldehydes with an anti selectivity (Scheme 13.17). 

Homoallylic alcohols (8, 111-112). CrCl2, prepared in situ by reduction of CrCl, (Strem) in THF with Na/Hg, is superior to CrCl2 prepared by reduction of CrCl, with LiAlHj for the Cr(II)-mediated addition of crotyl halides to aldehydes. The homoallylic alcohols are formed in good yield and with high arm-selectivity.7 Example ... 

The Claisen rearrangement goes through a transition state in the chair conformation. This is the supported by the fact that trans, trans-crotyl propenyl ether gave more than 97% of the threo aldehyde showing a preference for the chair form while reaction in the boat gave mainly erythro aldehyde. 

The observation that aldehyde diastereoface selection is interrelated with allylborane geometry has important implications for the related aldol processes. The reactions of (-)-180a and (-)-180b with both enantiomers of aldehyde 181 revealed both consonant and dissonant double stereodifferentiation. For the Cram-selective ( )-crotyl... 

Scheme 11 Carbonyl tert-prenylation, crotylation, and allylation from the aldehyde or alcohol oxidation level under the conditions or iridium-catalyzed transfer hydrogenation...

More recently, using the cyclometallated iridium C,(7-benzoate derived from allyl acetate, 4-methoxy-3-nitrobenzoic acid and BIPHEP, catalytic carbonyl crotylation employing 1,3-butadiene from the aldehyde, or alcohol oxidation was achieved under transfer hydrogenation conditions [274]. Carbonyl addition occurs with roughly equal facility from the alcohol or aldehyde oxidation level. However, products are obtained as diastereomeric mixtures. Stereoselective variants of these processes are under development. It should be noted that under the conditions of ruthenium-catalyzed transfer hydrogenation, conjugated dienes, including butadiene, couple to alcohols or aldehydes to provide either products of carbonyl crotylation or p,y-enones (Scheme 16) [275, 276]. 

Scheme 24 Enantioselective carbonyl crotylation from the alcohol or aldehyde oxidation level via iridium-catalyzed C-C bond-forming transfer hydrogenation...

Unsaturated aliphatic aldehydes were selectively reduced to unsaturated alcohols by specially controlled catalytic hydrogenation. Citral treated with hydrogen over platinum dioxide in the presence of ferrous chloride or sulfate and zinc acetate at room temperature and 3.5 atm was reduced only at the carbonyl group and gave geraniol (3,7-dimethyl-2,6-octadienol) [59], and crotonaldehyde on hydrogenation over 5% osmium on charcoal gave crotyl alcohol [763]. 

Complex hydrides can be used for the selective reduction of the carbonyl group although some of them, especially lithium aluminum hydride, may reduce the a, -conjugated double bond as well. Crotonaldehyde was converted to crotyl alcohol by reduction with lithium aluminum hydride [55], magnesium aluminum hydride [577], lithium borohydride [750], sodium boro-hydride [751], sodium trimethoxyborohydride [99], diphenylstarmane [114] and 9-borabicyclo[3,3,l]nonane [764]. A dependable way to convert a, -un-saturated aldehydes to unsaturated alcohols is the Meerwein-Ponndorf reduction [765]. 

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