Diastereoselective Addition of Organocerium(III) Reagents Derived from 3-Substituted Propargyl Bromides to Aldehydes

Abstract

Abstract:Various cerium allenyl reagents were generated by transmetallation of allenyl Grignard compounds with CeCl 3 and subsequent conversion into homopropargylic alcohols by addition to various aliphatic and aromatic aldehydes. The a-acetylenic alcohols were obtained with regioselectivities and diastereoselectivities up to 98% de in favor of the threo-diastereomers.Key words: lanthanides, organometallic reagents, addition reactions, diastereoselectivity, regioselectivityThe importance of allenic anions in synthetic organic chemistry arises from their utility in C-C bond forming reactions such as additions to carbonyl groups.2 The resulting homopropargylic alcohols are key intermediates in the synthesis of g-butyrolactones 3 and polyketide natural products. 4 As ambident nucleophiles allenic anions add to carbonyl groups giving rise to two products, b-acetylenic and a-allenic alcohols.5 Furthermore, the products can be formed as mixtures of two diastereomers. Thus, to achieve a selective reaction, it is necessary to control the regioand stereochemistry at the same time. Structure and reactivities of the ambident anions are highly dependent on the nature of the counter cation (Scheme 1). 6Scheme 1 Generation of the organocerium(III) allenyl compounds In the course of our studies in natural product synthesis of compounds such as ergosterol 7 and its 4-substituted derivatives we examined the influence of different cerium(III) species.8 After transmetallation of the Grignard reagent prepared from 1-(trimethylsilyl)propargyl bromide with CeCl 3 or Ce(Oi-Pr) 3 , no change in the regioselectivity but an enormous improvement of the diastereoselectivity of the carbonyl addition reaction was observed in comparison to the Grignard reagent.Because of the outstanding diastereoselectivities often reached with organocerium compounds in addition reactions to carbonyl groups, 9 we investigated the suitability of these organometallics for a diastereoselective synthesis of b-acetylenic alcohols (Scheme 2, Table 2). Scheme 2 Reaction of organocerium(III)allenyls with aldehydesBased on earlier results 8 we chose Ce(Oi-Pr) 3 as cerium reagent, whereas benzaldehyde and 3-bromo-1-(trimethylsilyl)but-1-yne (1) 10 were selected as model compounds to optimize the reaction conditions. First, we decided to study the effect of the reaction temperature on yield and selectivity of the addition. The results are shown in Table 1.Addition of the benzaldehyde to the organocerium reagent at -78°C followed by warming to room temperature within 16 hours afforded the homopropargylic alcohols 5a and 5b in 50% yield with a regioisomeric ratio of >98:2 and a diastereomeric ratio of 66:34 (entry 1). In addition, benzyl alcohol was formed among other by-products. The same reaction at 0°C followed by warming to room temperature within two hours afforded 5a and 5b in an overall yield of 72% with unchanged regioselectivity and a diastereomeric ratio of 72:28. Only traces of benzyl alcohol could be found. Using these reaction conditions, we studied as next t...

Applications of CeCl3 as an Environmental Friendly Promoter in Organic Chemistry

“…The importance of γ-butyrolactones in synthetic organic chemistry 85 is the foundation of a useful method for the synthesis of threo-homopropargylic alcohols 38, key intermediates for the synthesis of heterocyclic targets (Scheme 14). 86 The authors found that, after formation of allenyl Grignard compounds/CeCl 3 complexes 37, these reacted with various aliphatic and aromatic aldehydes to give the corresponding homopropargylic alcohols. The alcohol adducts have been obtained with threo/erythro ratios ranging from 65:35 to >98:2, and higher regio-and diastereoselectivities have been achieved in reactions promoted by CeCl 3 than other cerium(III) salts such as Ce(OPr i ) 3 .…”

Addition of Hetero Allenyl Copper Reagents to Aldehydes: Scope and Behavior

“…Reactions of allenyl metals with aldehydes to give the corresponding homopropargylic alcohols have been studied extensively . Various derivatives such as allenyl lithium, magnesium, aluminum, zinc, boron, cerium, or titanium have been successively tested with poor to high regio- and diastereoselectivity, depending on the nature of the allenyl moiety substituent. Excellent and general results have been reported by Marshall for the use of isolated alkyl-substituted allenyl tin derivatives .…”

How easy are the syntheses of allenes?

“…Allenyl or propargylic organometallic reagents, 112 such as propargylic lithium, 113 boron, 114 silicon, 115 and tin derivatives, 116 reacted with carbonyl or related compounds, 117 including imine and oxocarbenium ion, 118 giving a-allenic alcohols or related compounds. In addition, a variety of other propargylic/ allenic organometallic reagents including titanium, 119 indium, 120 aluminum, 121 zinc, 122 samarium, 123 cerium, 124 and antimony, 125 have also been found suitable for this reaction. As a special case, aldehydes interacted with alcohols in the presence of Lewis acids forming more electrophilic oxocarbenium ion species, which upon interception by nucleophilic propargyl reagents, such as propargylsilanes, afforded allenyl ether compounds.…”