Hydroformylation, stereoselective aldehydes

The hydroformylation reaction ( oxo reaction ) of alkenes with hydrogen and carbon monoxide is established as an important industrial tool for the production of aldehydes ( oxo aldehydes ) and products derived there from [1-6]. This method also leads to synthetically useful aldehydes and more recently is widely applied in the synthesis of more complex target molecules [7-15,17], including stereoselective and asymmetric syntheses [18-22]. 

The approach to polyketide synthesis described in Scheme 5.2 requires the relatively nontrivial synthesis of acid-sensitive enol acetals 1. An alternative can be envisioned wherein hemiacetals derived from homoallylic alcohols and aldehydes undergo dia-stereoselective oxymercuration. Transmetallation to rhodium could then intercept the hydroformylation pathway and lead to formylation to produce aldehydes 2. This proposal has been reduced to practice as shown in Scheme 5.6. For example, Yb(OTf)3-cata-lyzed oxymercuration of the illustrated homoallyhc alcohol provided organomercurial 14 [6]. Rhodium(l)-catalyzed hydroformylation of 14 proved successful, giving aldehyde 15, but was highly dependent on the use of exactly 0.5 equiv of DABCO as an additive [7]. Several other amines and diamines were examined with variation of the stoichiometry and none proved nearly as effective in promoting the reaction. This remarkable effect has been ascribed to the facilitation of transmetallation by formation of a 2 1 R-HgCl DABCO complex and the unique properties of DABCO when both amines are complexed/protonated. 

In the hydroformylation of optically active alkenes, all aldehydes were shown to be formed with predominant retention of configuration.53,54 This was interpreted to prove, in accordance with the transformation of deuterium labeled alkenes,55 56 that stereoselective hydrogen shifts of the coordinated olefins occur without dissociation of the isomeric alkenes.30... 

Stoichioinetric deuterioformylation of bicyclo[2.2.1]hcpt-2-ene with cobalt tetracarbonyl deuteride gives the exo-product in only 20% yield122. Hydroformylation of substituted cyclo-propenes stereoselectively leads to formylcyclopropanes. Thus, 2,3-diphenyl-2-cyclopropene-carboxylic acid esters give exclusively the 2-formyl-2,3-diphenylcyclopropanecarboxylic acid esters with the aldehyde group cis to the ester group114,122. 

Other chirally modified platinum, cobalt and rhodium complexes give lower inductions, although sometimes with higher aldehyde and branched product yields (Table 1). A strong dependance of chemo-, regio- and stereoselectivity on reaction conditions and conversion rates is observed, sometimes with contradictory results. Attempts to optimize the chemo- and re-gioselectivity usually lead to lower asymmetric inductions. Moreover, since double-bond isomerization and racemization take place under hydroformylation conditions, the results reported do not necessarily reflect the primary asymmetric induction of the starting alkene. 

It catalyses the aminolysis of epoxides in an extraordinarily efficient manner in aprotic solvents (e.g. toluene, CH2CI2) with complete trans stereoselectivity and high regioselectivity [Chini et al. Tetrahedron Lett 35 433 1994], It also catalyses the trans addition of indole (at position 3) to epoxides (e.g. to phenoxymetltyloxirane) in >50% yields at 60° (42 hours) under pressure (10 Kbar) and was successfully applied for an enantioselective synthesis of (+)-diolmycin A2 [Kotsuki Tetrahedron Lett 37 3727 799(5]. Of the ten lanthanide triflates, Yb(OTf)3 gave the highest yields (> 90%, see above) of condensation products by catalytically activating formaldehyde, and a variety of aldehydes, in hydroformylations and aldol reactions, respectively, with trimethylsilyl enol-ethers in THF at room temperature. All the lanthanide triflates can be recovered from these reactions for re-use. [Kobayashi Hachiya J Org Chem 59 3590 1994.]... 

The synthesis began with Yb(OTf)3-catalyzed oxymercuration [88] of ho-moallyUc alcohol 204 [89], prepared by asymmetric allylation with Brown s reagent, to generate organomercury chloride 205. Rh(I)-catalyzed formy-lation [90] of 205 in the presence of DABCO (0.5 equiv.) furnished aldehyde 206. Stereoselective crotylation of 206 via Brown s reagent, followed by regioselective Rh(I)-catalyzed hydroformylation provided lactol 203. Dia-... 

Control of selectivity, chemo-, regio-, and stereoselectivity, is the most important problem in the hydroformylation reaction. As far as chemoselectivity is concerned such competitive reactions as isomerization, double bond hydrogenation and aldehyde hydrogenation occur under hydroformylation conditions. 

Dihydroxy aldehydes 54 are also stereoselectively prepared by hydroformylation of enol ether 52 (R = H, Me, Pr, BnOCCH ), R = Bu, Me). This suppose an alternative procedure to the aldol reaction, (Figure 17) [45,46],... 

Double bonds not directly bonded to cycles can also be stereoselectively hydroformylated, but there must be an efficient sterical discrimination of both faces of the double bond must. This is the case of l-methylvinyl-C-(3-glucoside 71 which is hydroformylated to give a 2-substituted aldehyde 72 in excellent yield and diastereoselectivity of 99% (Figure 21) [50]. The bulky substituent at position 2 of sugar blocks the conformation shown in 71 and forces the rhodium to be coordinated from the back face of the double bond. 

Under hydroformylation conditions and in the presence of Ph3P=CHCOR, compound 189 leads to the oxo derivative 190. The process involves a sequence of reactions that includes initial hydroformylation to give the aldehyde 191 in a stereoselective way (see also Figme 26), Wittig olefination to give the trans conjugated alkene 192 and hydrogenation. 

Also in the rhodium catalyzed hydroformylation of vinyl carbonates with biden-tate phosphine-phosphite complexes, the a-aldehyde was favored a/p = 92 8), which opens up the possibility of running the reaction in a stereoselective manner [41]. 

Abstract Intramolecular allylboration of a>oxo-2-alkenylboronates allows the stereoselective formation of 2-vinyl-cycloalkanols. When heteroatoms are present in the chain linking the aldehyde and allylboronate functions a variety of saturated heterocycles with a stereodefined pattern of substituents may be prepared in this manner. Rapid assembly of anellated heterocycles becomes possible by domino-hydroformylation-allylboration-hydroformylalion cascade reactions. 

---