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In Organic Chemistry (2nd ed.) by Clayden, Greeves, and Warren, it is stated that (p 869)

[...] the enolates of some metals [Sn(II), Zr, Ti] give syn aldols regardless of enolate geometry.

There are also literature examples of syn-selective Zr aldol reactions, e.g. Tetrahedron Lett. 1980, 21 (48), 4607–4610.

If they were to obey a simple Zimmerman–Traxler chair-like transition state model, as is applicable for Li or B enolates, then (Z)-enolates should give syn aldols and (E)-enolates anti aldols. How does the mechanism or stereochemical model differ for these enolates?

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  • $\begingroup$ Would you consider splitting this into three questions? I'd be keen to research and answer it, but I also think there's enough content to make one question per metal. Essentially I don't want to write an essay for one question ;) $\endgroup$ – orthocresol Dec 26 '18 at 1:23
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For most aldol reactions, the relative 1,2-diastereoselectivity is a consequence of the enolate geometry.*

Both tin and titanium enolates are easily formed, and have been shown to exist predominantly in the (Z) configuration.

When reacting a cyclic (Zimmerman Traxler) TS, its commonly observed that (Z) enolates afford 1,2-syn aldol adducts, due to the orientation of the enolate (the (Z) enolate always has an axial R-group).

The following examples are instructive. In both cases (tin or titanium), we first form a (Z) enolate using the conditions shown. When the aldehyde (R-CHO) is introduced, chelation using the metal organises the Zimmerman Traxler TS. The lowest energy TS possible is the one in which the aldehyde is arranged with its bulky R group equatorial, however the enolate cannot put the methyl group (in this case) equatorial, as the enolate geometry enforces its axial positioning. Following both transition states through, we get the 1,2-syn aldol adduct in both cases.#

Syn selective tin and titanium aldol reactions

Image taken from Andy Myers' CHEM115 Handout: Stereoselective, directed aldol reaction

The description given in Carey is fundamentally incorrect for the reactions shown (even if it does predict the correct product). Looking at the references he gives, they're all fairly old, before more recent experimental and computation studies have validated the cyclic TS model for these kinds of metal enolates.


*: Mukaiyama aldol reactions do not conform to this, since they occur via a fundamentally different transition state (an open TS) to the Zimmerman Traxler model commonly found for other aldol reactions.

#: In this case, we also get enantioselectivity via the use of a chiral auxiliary, and depending on the metal used the enantioselectivity can be switched around due to chelation or lack thereof between the auxiliary and the metal

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  • $\begingroup$ Is there any reason why (Z) is favoured? $\endgroup$ – orthocresol Jun 7 '17 at 19:20
  • $\begingroup$ @orthocresol. I was actually thinking of posting that as a question. I have never found a good model for why tin gives (Z). Lithium obeys the Ireland model, Boron has well defined models of its own. Tin, not so much! $\endgroup$ – NotEvans. Jun 7 '17 at 19:25
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    $\begingroup$ @orthocresol Just had a nice chat with NotEvans., but if memory serves me, the oxaziridinone's side chain creates a lot of strain for the (E)-enolate one the transition metal is coordinated to both carbonyl groups. I think that was one of the goals of the design for the oxaziridinone directing group. $\endgroup$ – Zhe Jun 7 '17 at 20:08
  • $\begingroup$ I've already realized that Carey, while being an excellent book, is pretty much outdated. By the way, Myers lectures are very interesting. $\endgroup$ – RBW Jun 7 '17 at 20:46
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In Carey, Sundberg Advanced Organic Chemistry it is stated:

This preference arises from avoidance of gauche interaction of the aldehyde group and the enolate beta-substituent. The syn stereoselectivity indicates that reaction occurs through an open TS.

The relevant conformations adopted by the two molecules in respect to each other, just before the reaction takes place are attached. The lower one, which leads to the anti aldol, has the energy increasing gauche interaction (the R groups may differ):

enter image description here

Therefore is doesn't matter whether the enolate configuration is Z or E, the syn aldol will be obtained stereoselectively.

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