Highly Enantioselective Alk‐2‐enylation of Aldehydes through an Allyl‐Transfer Reaction

Abstract

The enantioselective allylation of aldehydes to prepare optically pure homoallylic alcohols is one of the most attractive and popular methods for the construction of stereogenic centers [Eq. (1)]. [1, 2d] Not only can this type of reaction provide homoallylic alcohols with high enantiomeric purity, it can also provide modified chiral building blocks after suitable functionalization of the C À C double bond in the introduced allylic unit.Highly enantiopure homoallylic alcohols have been prepared by using allylic organometallic reagents (MCH 2 CH¼CH 2 ; M = metal) and a stoichiometric amount of a chiral auxiliary [3] or a catalytic amount of a chiral promoter. [4] Furthermore, allylation reactions with g-substituted organometallic reagents 4 in the presence of a chiral auxiliary or catalyst afford the g adduct 5 diastereo-and enantioselectively. [5] This CÀC-bond-formation reaction is particularly useful for the construction of vicinal stereogenic centers in a flexible hydrocarbon chain [Eq. (2)].However, to the best of our knowledge, no asymmetric alk-2-enylation reaction (e.g. crotylation) of aldehydes to give 4-substituted homoallylic alcohols 6 (a adduct) has yet been reported [Eq. (3)]. This is because the allylation reactions by alk-2-enyl metal reagents 4 proceed, without exception, with allylic transposition via a six-membered cyclic transition state, affording exclusively the g adduct 5. [6] Recently we discovered an efficient and stereoselective nucleophilic alk-2-enylation reaction of aldehydes that produces the desired a adduct 6. In this procedure, no allylic metal nucleophiles are involved, and a homoallylic alcohol 7 acts as an allyl donor. This unusual allylation reaction appears to proceed through a 2-oxonium [3,3] sigmatropic rearrangement, as shown in Scheme 1. [2a] The acid-catalyzed reaction of aldehyde 1 with the homoallylic alcohol (g adduct) 7 stereoselectively gave the homoallylic alcohol a adduct 6 by an allyl transfer from 7 via hemiacetal (H 1 ) and oxonium cations T 1 and T 2 .More importantly, the Sn(OTf) 2 -catalyzed (10 mol %) reaction of 3-phenylpropanal (1 a) with optically pure allyl donor (3R,4S)-1-phenyl-4-methylhex-5-en-3-ol (5 a; > 99 % ee) gave (3S)-1-phenylhept-5-en-3-ol (6 a) in 85% yield with > 98 % ee (Scheme 2). [2b,c]

Systematic Synthesis of Diphenyl‐Substituted Carotenoids as Molecular Wires

“…The indium‐mediated addition of chloroallylic sulfone 11a (R 2 = Ph, R 3 = H, Scheme ) to benzaldehyde produced homoallylic alcohol 22ā with high syn (OH and CH 2 SO 2 Ph) selectivity (>11:1), which underwent oxonia‐Cope rearrangement, at 80 °C in the presence of stoichiometric camphorsulfonic acid (CSA) and benzaldehyde to yield 5ā (Scheme ), as was previously reported . (2 Z ,4 E )‐Dienyl sulfone 5ā (X = H) with a phenyl substituent at C‐2 was obtained in a reasonable yield (ca.…”

“…A catalytic amount (10 mol‐%) of the Lewis acid Sn(OTf) 2 can induce this rearrangement at 40 °C . The stereoselectivity ( Z/E = 3.5:1) did not deteriorate in the absence of added aldehyde under these conditions, but a decrease in the yield of 6ā (49 %) due to fragmentation (21 % of 24 ) was still noticed (entry 4).…”

Biology‐Oriented Synthesis of Stereochemically Diverse Natural‐Product‐Derived Compound Collections by Iterative Allylations on a Solid Support

“…[32] The synthesis of these natural products and their analogues was conducted on both Wang and silyl linker. It started with the solution-phase synthesis of the homoallylic alcohols (R)-and (S)-55 (Scheme 6), which were synthesized in solution by applying l-Ipc 2 BAll, a Keck allylation, [33] or the Nokami crotyl-transfer method [34] (Table 3). In our hands, the use of a Ti-BINOL (BINOL = 1,1'-bi-2-naphthol) catalyst furnished variable results with respect to yield and selectivity, but after some experimentation, reaction conditions recently reported by Kurosu et al [33b] turned out to be suitable (entry 2).…”

Solid‐Phase Synthesis of [5.5]‐Spiroketals

“…For the solid-phase synthesis of the b-hydroxy aldehydes 7 the chiral homoallylic alcohols 16-23 [25] and 15a and 15b [26] were synthesised following known procedures (Scheme 4). In addition, commercially avail-able 3-buten-1-ol 14 and b-hydroxy esters 24a, 24b, 25a and 25b [27] were appropriate starting materials.…”