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Abstract: A planned total synthesis of photosynthetic tetrapyrrole macrocycles installs essential stereochemical features in early precursors via established asymmetric methodology. Key building blocks are dihydrodipyrrins that contain a chiral pyrroline unit, for which chiral hex-5-yn-2-ones are valuable precursors. Chiral hex-5-yn-2-ones bearing diverse functional groups at the 1-position were sought that correspond to the chiral pyrroline units (rings B and D) of bacteriochlorophyll a. Three main results are reported herein. First, (2R,3R)-3-ethyl-2-methylpent-4-ynoic acid, prepared via a Schreiber-modified Nicholas reaction, was converted to the analogous chiral Weinreb pentynamide. The latter was treated with tributyltin-one-carbon synthons to create a 1-hydroxyhex-5-yn-2-one scaffold containing the two requisite stereocenters and with the newly introduced hydroxy group in free form or protected as the Me, MOM, THP, MEM, Bn, or SEM derivative. Second, improved routes to intermediates on the path to the pre-B compound, (3R,4R)-1,1-dimethoxy-3-ethyl-4-methylhex-5-yn-2-one, were developed, in part by derivatization of the chiral Weinreb pentynamide. Third, one (semisynthetic) chiral hexynone bearing a native phytyl substituent, a near-universal precursor to ring D of photosynthetic hydroporphyrins, was prepared in 2.5 mmol quantity. The synthesis and manipulation were achieved while maintaining stereochemical integrity in these somewhat densely functionalized chiral hexynones (three functional groups and two stereocenters in a six-carbon scaffold). Altogether, 22 new compounds have been prepared, including 15 chiral hexynones for studies in (bacterio)chlorophyll synthetic methodology. The chiral hexynones were prepared in quantities ranging from 0.11–12 mmol as required for exploratory and/or preparative studies.